Catalogue of Research Project Proposals and Potential Participants Results of the MedResIn Web-Survey The survey is open for further contribution. Please visit: http://www.meduni-graz.at/medresin Editorial This catalogue was assembled from research profiles provided in the on-line survey of MedResIn at http://www.meduni-graz.at/medresin/profiles.html. It is understood that all information provided is part of the intellectual property of the submitter. Disclaimer Please note that the responsibility for the content and formulation of the abstracts lies with the submitters of the abstracts. All content of the MedResIn survey has been compiled carefully. The Medical University of Graz makes no guarantees of accuracy, completeness and timeliness of the information provided by the participants. Therefore the Medical University of Graz accepts no responsibility or liability for damages or losses resulting from the use of this website. Contact Dr. Carolin Auer Medical University of Graz http://www.meduni-graz.at/medresin Introduction The Specific Support Action "Medical Research Initiative South Eastern Europe MedResIn" has been set up to strengthen scientific & technological interaction and cooperation in biomedical research between the EU and South Eastern Europe, especially the Western Balkan countries. Its aim is to facilitate future participation of Medical Universities/Faculties and Schools from Western Balkan countries in the relevant Priorities of the European Framework Programmes. Specifically, it is targeted towards creating a platform for the transition to FP7 in order to provide best possible starting conditions for biomedical research in Western Balkan countries, thus supporting their integration into the European Research Area (ERA). The MedResIn project endeavors to increase visibility & accessibility of biomedical research communities from Western Balkan countries in Europe; increase the access of Western Balkan countries biomedical research communities to the FP by providing tailor-made capacity building measures following their specific needs; support the development of joint EU research projects including partners from Western Balkan countries; build up a sustainable network of institutions which will keep up co-operation; better, faster and balanced implementation of Life Sciences and biomedical research-related priorities of the FP in Western Balkan countries. The MedResIn extended consortium currently consists of partners from 8 countries, including Western Balkan participants as well as EU member states. The initiative is managed by a core consortium of 6 partners: Medical University of Graz (Coordinator) University of Maribor, Medical Faculty University of Zagreb, School of Dental Medicine University of Belgrade, Medical Faculty RTD Services University of Padova, Medical Faculty Table of Contents Institutional Profiles 8 Individual Profiles of Researchers and Teams Anesthaesiology Anatomy Bacteriology Biochemistry Biology Biophysics Clinical Chemistry Clinical Microbiology Cytology Dentistry Dermatology Epidemiology Genetics Immunology and Immunohaematology Information Technology Internal Medicine Microbiology Neurology Obstetrics and Gynaecology Other Allied Sciences Pathology Pediatrics Pharmacology Physiology Psychiatry Public Health Services Radiology Social Medicine Surgery Therapeutics Toxicology 55 56 57 64 66 89 104 107 108 110 114 130 131 140 168 186 189 209 215 217 219 220 228 234 244 254 256 263 268 269 282 293 Institutions Institutions Institution/University Name of Institution/University Brodarski Institute Number of Employees 170 Number of Researchers 50 Country Croatia Postal Adress Av. V. Holjevca 20 10020 Zagreb Projects Domestic Projects 7 International Projects Contact Person Name Email [email protected] Function Phone +385 1 6504110 Fax +385 1 6504280 Website www.hrbi.hr Research Team Objectives Main Fields thermal analysis of materials Partners/Interests Institutions Institution/University Name of Institution/University Children´s Hospital Zagreb Number of Employees 638 Number of Researchers Country Croatia Postal Adress Klaićeva 16 10000 Zagreb Projects Domestic Projects 6 International Projects 4 Contact Person Name Email [email protected] Function Phone +385 1 4600100 Fax +385 1 4826053 Website http://kdb.hr Research Team Objectives Main Fields biomedicine, health, paediatrics Partners/Interests biomedicine, health, paediatrics Institutions Institution/University Name of Institution/University Clinic for Traumatology Number of Employees 447 Number of Researchers 18 Country Croatia Postal Adress Draškovićeva 19 10000 Zagreb Projects Domestic Projects 2 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4697000 Fax +385 1 4610365 Website www.trauma.hr Research Team Objectives Main Fields biomedicine and health, biology, biotechnology Partners/Interests clinical biomedicine, biochemistry, biotechnology Institutions Institution/University Name of Institution/University Clinical Hospital “Karlovac” Number of Employees 889 Number of Researchers 20 Country Croatia Postal Adress A. Štampara 3 47000 Karlovac Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 47 608100 Fax +385 47 431337 Website Research Team Objectives Main Fields biomedicine and health Partners/Interests oncology, immunology, genetics, endocrinology, clinical chemistry, ophthalmology, cardiology & vascular diseases, metabolism, dermatology, neuroscience, traumatology, urology Institutions Institution/University Name of Institution/University Clinical Hopital “Merkur” Number of Employees 820 Number of Researchers Country Croatia Postal Adress Zajčeva 19, p.o. box 414 10000 Zagreb Projects Domestic Projects 6 International Projects Contact Person Name Email [email protected] Function Phone +385 1 2431396 Fax +385 1 2431402 Website www.kb-merkur.hr Research Team Objectives Main Fields biomedicine and health Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital “Osijek” Number of Employees 2802 Number of Researchers 114 Country Croatia Postal Adress Josipa Huttlera 4 31000 Osijek Projects Domestic Projects 5 International Projects Contact Person Name Email [email protected] Function Phone +385 31 511106 Fax +385 31 512235 Website www.kbo.hr Research Team Objectives Main Fields biomedicine and health Partners/Interests biomedicine and health Institutions Institution/University Name of Institution/University Clinical Hospital “Požega” Number of Employees 507 Number of Researchers 19 Country Croatia Postal Adress Osječka 107 34000 Požega Projects Domestic Projects 5 International Projects 2 Contact Person Name Email [email protected] Function Phone +385 34 254555 Fax +385 34 271713 Website Research Team Objectives Main Fields biomedicine and health Partners/Interests oncology, immunology, genetics, endocrinology, clinical chemistry, ophthalmology, cardiology & vascular diseases, metabolism, dermatology, neuroscience Institutions Institution/University Name of Institution/University Clinical Hospital “Sisters of charity” Number of Employees 2293 Number of Researchers 116 Country Croatia Postal Adress Vinogradska cesta 29 10000 Zagreb Projects Domestic Projects 22 International Projects Contact Person Name Email [email protected] Function Phone +385 1 3787110 Fax +385 1 3768269 Website www.kbsm.hr Research Team Objectives Main Fields biomedicine Partners/Interests oncology, immunology, genetics, endocrinology, clinical chemistry, ophthalmology, cardiology & vascular diseases, metabolism, dermatology, neuroscience Institutions Institution/University Name of Institution/University Clinical Hospital “Split” Number of Employees 3120 Number of Researchers 158 Country Croatia Postal Adress Spinčećeva 1 21000 Split Projects Domestic Projects 7 International Projects 1 Contact Person Name Email [email protected] Function Phone +385 21 556111 Fax +385 21 365738 Website www.kbsplit.hr Research Team Objectives Main Fields biomedicine, clinical medicine, public health Partners/Interests partners with similar research interests, multicentric clinical studies interventional radiology, cardiology, oncology, molecular pathology, nephrology, ophthalmology, gynecology, endoscopic surgery, hepatitis, war effect on health, glucose-6-phosphate deficiency, asbestosis Institutions Institution/University Name of Institution/University Clinical Hospital “Sveti Duh” Number of Employees 1311 Number of Researchers 34 Country Croatia Postal Adress Sveti Duh 64 10000 Zagreb Projects Domestic Projects 9 International Projects 78 Contact Person Name Email [email protected] Function Phone +385 1 3712111 Fax +385 1 3712308 Website www.obsd.hr Research Team Objectives Main Fields perinatology, otorinolanringology, neurology, urology gynecology, ophthalmology, surgery, internal medicine Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hopital Center Zagreb Number of Employees 4431 Number of Researchers 56 Country Croatia Postal Adress Šalata 2 10000 Zagreb Projects Domestic Projects 15 International Projects 86 Contact Person Name Email [email protected] Function Phone +385 1 4920019 Fax +385 1 4818457 Website www.kbc-zagreb.hr Research Team Objectives Main Fields biomedicine Partners/Interests oncology, immunology, genetics, endocrinology, clinical chemistry, ophthalmology, cardiology & vascular diseases, metabolism, dermatology, neuroscience, oral medicine, denta materials, orthodontics, periodontology Institutions Institution/University Name of Institution/University Clinical Hospital for Chronic Diseases in Children- Zagreb Number of Employees 150 Number of Researchers 12 Country Croatia Postal Adress Srebrnjak 100 10000 Zagreb Projects Domestic Projects 1 International Projects 2 Contact Person Name Email [email protected] Function Phone +385 1 2430783 Fax +385 1 2430784 Website www. .hr Research Team Objectives Main Fields biomedicine, pharmacy, biochemistry Partners/Interests biomedicine, pharmacy, biochemistry Institutions Institution/University Name of Institution/University Clinical Hospital for Diabetes, Endocrinology and Metabolic Diseases “Vuk Vrhovec” Number of Employees 258 Number of Researchers 32 Country Croatia Postal Adress Dugi Dol 4a 10000 Zagreb Projects Domestic Projects 6 International Projects 2 Contact Person Name Email [email protected] Function Phone +385 1 2353800 Fax +385 1 2331515 Website www.idb.hr Research Team Objectives Main Fields biomedicine, diabetology, endocrinology, behavioural medicine Partners/Interests research areas related to diabetes and endocrinological diseases biomedicine, diabetology, endocrinology, behavioural medicine Institutions Institution/University Name of Institution/University Clinical Hospital for Psychiatry “Sveti Ivan” Number of Employees 320 Number of Researchers 9 Country Croatia Postal Adress Jankomir 1 10090 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 3430000 Fax +385 1 3794116 Website www.pbsvi.hr Research Team Objectives Main Fields biomedicine, psychiatry, psychosis, alcoholism Partners/Interests biomedicine, psychiatry, psychosis, alcoholism Institutions Institution/University Name of Institution/University Clinical Hospital for Tumors Number of Employees 434 Number of Researchers 39 Country Croatia Postal Adress Ilica 197 10000 Zagreb Projects Domestic Projects 3 International Projects Contact Person Name Email [email protected] Function Phone +385 1 3783555 Fax +385 1 3775536 Website www.kzt.hr Research Team Objectives Main Fields oncology Partners/Interests oncology Institutions Institution/University Name of Institution/University Croatian Institute for Brain Research Number of Employees 28 Number of Researchers 5 Country Croatia Postal Adress Šalata 12 10000 Zagreb Projects Domestic Projects 41 International Projects 14 Contact Person Name Email [email protected] Function Phone +385 1 4596902 Fax +385 1 459642 Website www.hiim.hr Research Team Objectives Main Fields brain research Partners/Interests research areas related to brain research inquiry including normal development of the human cerebral cortex, developmental brain disorders, signalling mechanisms and molecules in the developing and adult brain, the CSF pathophysiology and hydrocephalus, neurodegenerative diseases and schizophrenia, brain plasticity and repair after perinatal hypoxic/ischaemic lesions in premature infants Institutions Institution/University Name of Institution/University Croatian Veterinary Institute Number of Employees 203 Number of Researchers 45 Country Croatia Postal Adress Savska cesta 143, p.o. box 883 10000 Zagreb Projects Domestic Projects 8 International Projects Contact Person Name Email [email protected] Function Phone +385 1 6190845 Fax +385 1 6190841 Website www.veinst.hr Research Team Objectives Main Fields veterinary medicine Partners/Interests veterinary medicine Institutions Institution/University Name of Institution/University Faculty of Medicine of the University of Osijek Number of Employees 113 Number of Researchers 89 Country Croatia Postal Adress Josipa Huttlera 4, p.o. box 392 31000 Osijek Projects Domestic Projects 21 International Projects 4 Contact Person Name Email [email protected] Function Phone +385 31 512888 Fax +385 31 512833 Website www.mefos.hr Research Team Objectives Main Fields biomedicine and health, biochemistry, physics, physiology and immunology, biometrics and biomechanics, genetics and forensic medicine, pharmacology of pain, neurobiology, embryology, nanomedicine Partners/Interests basic and clinical medical sciences, industry physiology, general and cardiovascular physiology, genetics, pharmacology, immunology (kidney transplantation), basic medical sciences, gastroenterology, cardiology, neurology, psychiatry Institutions Institution/University Name of Institution/University Faculty of Medicine of the University of Rijeka Number of Employees 495 Number of Researchers 338 Country Croatia Postal Adress Braće Branchetta 20 51000 Rijeka Projects Domestic Projects 52 International Projects Contact Person Name Email [email protected] Function Phone +385 51 65111 Fax +385 51 675806 Website www.medri.hr Research Team Objectives Main Fields biomedicine and health, oral science Partners/Interests oral sciences temporomandibular disorders, dental materials, biological effects of dental materials, root channel instrumentation, apex locators, influence of restorative procedures on dental pulp, chronic orofacial pain, esthetic fixed prostethic dentistry, periodontology, cariology, clinical antrophology, morphometric, and craniometric analysis of malocclusion, dental traumatology, oral health in children with (and without) disabilities, early childhood caries Institutions Institution/University Name of Institution/University Faculty of Pharmacy and Biochemistry of the University of Zagreb Number of Employees 11,3 Number of Researchers 82 Country Croatia Postal Adress A. Kovačića 1, p.o. box 156 10000 Zagreb Projects Domestic Projects 20 International Projects 14 Contact Person Name Email [email protected] Function Phone +385 1 4856201 Fax +385 1 4856201 Website www.pharma.hr Research Team Objectives Main Fields pharmacy, biochemistry, molecular biology, chemistry Partners/Interests pharmacy, biochemistry, molecular biology, chemistry Institutions Institution/University Name of Institution/University Faculty of Veterinary Medicine of the University of Zagreb Number of Employees 318 Number of Researchers 162 Country Croatia Postal Adress Heinzelova 55 10000 Zagreb Projects Domestic Projects 46 International Projects 13 Contact Person Name Email [email protected] Function Phone +385 1 2390111 Fax +385 1 2441390 Website www.vef.hr Research Team Objectives Main Fields veterinary medicine Partners/Interests veterinary medicine Institutions Institution/University Name of Institution/University Institute for Medical Research and Occupational Health Number of Employees 150 Number of Researchers 51 Country Croatia Postal Adress Ksaverska cesta 2, p.o.box 291 10000 Zagreb Projects Domestic Projects 29 International Projects 12 Contact Person Name Email [email protected] Function Phone +385 1 4673188 Fax +385 1 4673303 Website www.imi.hr Research Team Objectives Main Fields working and living environment, hygiene, health and dissemination of knowledge on industrial hygiene, environmental population and radiation Partners/Interests biomedicine, ecology, biology, hygiene Institutions Institution/University Name of Institution/University Institute of Immunology, Inc. Number of Employees 360 Number of Researchers 75 Country Croatia Postal Adress Rockefellerova 2. p.o. box 266 10000 Zagreb Projects Domestic Projects 6 International Projects 2 Contact Person Name Email [email protected] Function Phone +385 1 4684500 Fax +385 1 468433 Website www.imz.hr Research Team Objectives Main Fields molecular biomedicine, cellular immunology, radioimmunology and chemistry Partners/Interests immunology, biochemistry Institutions Institution/University Name of Institution/University PLIVA Research Institute Ltd. Number of Employees 130 Number of Researchers 97 Country Croatia Postal Adress Prilaz baruna Filipovica 29 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 37211889 Fax +385 1 3721534 Website www.pliva.hr Research Team Objectives Main Fields medical chemistry, pharmacology, biology, drug design, preclinical research Partners/Interests medical chemistry, pharmacology, biology, drug design, preclinical research Institutions Institution/University Name of Institution/University Public Health Institute Number of Employees 408 Number of Researchers 33 Country Croatia Postal Adress Mirogojska cesta 16 10000 Zagreb Projects Domestic Projects 1 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4696151 Fax +385 1 4678002 Website www.publichealth-zagreb.hr Research Team Objectives Main Fields public health, biology Partners/Interests Institutions Institution/University Name of Institution/University Ruđer Bošković Institute Number of Employees 824 Number of Researchers 516 Country Croatia Postal Adress Bijenička cesta 54, p.o. box 180 10000 Zagreb Projects Domestic Projects 125 International Projects 59 Contact Person Name Email [email protected] Function Phone +385 1 4561111 Fax +385 1 4680084 Website www.irb.hr Research Team Objectives Main Fields biomedicine, biology, oceanography, physics, chemistry, computing, engineering Partners/Interests Institutions Institution/University UZAG Name of Institution/University School of Dental Medicine, University of Zagreb Number of Employees 256 Number of Researchers 146 Country Croatia Postal Adress Gunduliceva 5, p.o. box 756 10000 Zagreb Projects Domestic Projects 20 International Projects 2 Contact Person Name Email [email protected] Function Phone +385 1 4802123 Fax +385 1 4830804 Website www.sfzg.hr Research Team Objectives Main Fields oral sciences Partners/Interests oral sciences dental anthropology, oral medicine, dental materials, orthodontics, periodontology Institutions Institution/University Name of Institution/University School of Medicine University of Zagreb Number of Employees 763 Number of Researchers 495 Country Croatia Postal Adress Šalata 3 10000 Zagreb Projects Domestic Projects 120 International Projects 7 Contact Person Name Email [email protected] Function Phone +385 1 4566909 Fax +385 1 4566724 Website www.mef.hr Research Team Objectives Main Fields anatomy, anaesthesiology, cytology, histology, embryology, dermatology, epidemiology, pharmacology, toxicology, physical medicine and rehabilitation, physiology, genetics, gynecology, obstetrics, hygiene, immunology, internal medicine, public health, surgery, chemistry, biochemistry, microbiology, biology, neurology, neuroscience, nuclear medicine, ophthalmology, oncology, orthopedics, otorhynolaryngology, pathology, pediatrics, psychiatrics, radiology, social medicine, forensic medicine, urology, health ecology Partners/Interests anatomy, anaesthesiology, cytology, histology, embryology, dermatology, epidemiology, pharmacology, toxicology, physical medicine and rehabilitation, physiology, genetics, gynecology, obstetrics, hygiene, immunology, internal medicine, public health, surgery, chemistry, biochemistry, microbiology, biology, neurology, neuroscience, nuclear medicine, ophthalmology, oncology, orthopedics, otorhynolaryngology, pathology, pediatrics, psychiatrics, radiology, social medicine, forensic medicine, urology, health ecology Institutions Institution/University SUVAG Name of Institution/University Polyclinic for the Rehabilitation of Listening and Speech Number of Employees 264 Number of Researchers 40 Country Croatia Postal Adress Ul. Kneza Ljudevita Posavskog 10, p.o. box 617 10000 Zagreb Projects Domestic Projects 4 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4629600 Fax +385 1 4655166 Website www.suvag.hr Research Team Objectives Main Fields physiology of listening and speech, rehabilitation of listening an speech, cochlear implants Partners/Interests epidemiology, diagnostics and rehabilitation of listening and speech disorders Institutions Institution/University UMAR Name of Institution/University Faculty of Medicine, University of Maribor Number of Employees 28 Number of Researchers 15 Country Slovenia Postal Adress Slomškov trg 15 2000 Maribor Projects Domestic Projects 4 International Projects 3, EU 6-FP-IP PATHOGENCOMBAT FOOD-CT-2005-007081, EU 6FP-MEDRESIN-2005, Network for E-Learning in Medical Education eContentplus - IST Contact Person Name [email protected] [email protected] [email protected] Email Function +386 22345601 Phone +386 22345600 Fax www.mf.uni-mb.si Website Research Team Objectives Main Fields biomedicine Partners/Interests other biomedical research institutes Function of Endocrine Cells in Disease and Compensatory Processes - ARRS (prof. Rupnik) http://sicris.izum.si/search/rsr.aspx?lang=eng&id=7683&opt=3 Genetic Susceptibility to Gastrointestinal Complex Diseases and Pharmacogenomics - ARRS (doc. Potočnik) http://sicris.izum.si/search/rsr.aspx?opt=3&lang=eng&id=9398 PathogenCombat – EU 6th FP (doc. Cencič) http://www.pathogencombat.com/ Center of excellence – Biotechnology with pharmacy – EU Foundation for Regional Development (prof. Štrukelj) http://www.gov.si/euskladi/skladi/strukt_esrr_3.html Network for E-Learning in Medical Education eContentplus,(dr. Dinevski) http://europa.eu.int/information_society/activities/econtentplus/index_en.htm Incidence of erythropoietic protoporphyria and molecular mechanism in population of Slovenia - ARRS (prof. Krajnc) http://sicris.izum.si/search/rsr.aspx?lang=eng&id=4431&opt=3 Institutions Institution/University KOPA Name of Institution/University University Clinic of Respiratory of Allergic Diseases Number of Employees 454 Number of Researchers 50 Country Slovenia Postal Adress Golnik 36 4204 Golnik Projects Domestic Projects 10 International Projects 1,5FP EU BIOMED, No. QLRT-2001-0893 Contact Person Name Email [email protected] [email protected] Function Phone + 386 4 2569 111 Fax + 386 4 2569 117 Website www.klinika-golnik.si Research Team Objectives Main Fields Pulmology and Allergology Partners/Interests Institutions Institution/University Name of Institution/University General Hospital Ptuj Number of Employees Number of Researchers Country Slovenia Postal Adress Potrčeva 23-25 2250 Ptuj Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +386 2 749 14 00 Fax +386 2 749 16 30 Website Research Team Objectives Main Fields Dilatative Myocardiopathy Partners/Interests Institutions Institution/University Name of Institution/University General Hospital Maribor Number of Employees Number of Researchers Country Slovenia Postal Adress Ljubljanska 5 2000 Maribor Projects Domestic Projects International Projects Contact Person Name Email www.sb-mb.si/index.php?id=kontakt Function Phone + 386 2 32 11 000 Fax + 386 2 33 12 393 Website http://www.sb-mb.si/index.php?id=2 Research Team Objectives Main Fields Partners/Interests 1. Ph.D. Vlaisavljević Human reproduction (gynecology, andrology, perinatology, ultrasound, mammography, embryology laboratory, IVF, micromanipulation,genetics, diagnostics, breast diseases, infertility, endocrinology) http://sicris.izum.si/search/rsr.aspx?lang=eng&id=6601&opt=3 Project: Charactheristics of development, maturation and fertilization capacity of oocytes in ivf and icsi procedures in natural cycle, Acronym: J3-8764 (C) Duration: 1.1.1997 - 31.12.1999, Keywords: IVF, ICSI, natural cycle, fertilization, maturation in vitro, fertilization failure, follicleultrasound, follicle-Doppler, estradiol monitoring, Project: Cytogenetic analysis of human oocytes and preimplantation embryos Acronym: L3-5355 (C) Duration: 1.1.2003 - 31.12.2005 RANGE: 0,29 FTE Keywords: preimplantation genetic diagnosis, fluorescence in situ hybridization, oocytes, embryos Project: Value of transvaginal hydrolaparoscopy in infertility evaluation Acronym: L3-5246 (C) Duration: 1.1.2003 - 31.12.2005 RANGE: 0,29 FTE Keywords: transvaginal hydrolaparoscopy, hysterosalpingography, infertility evaluation Institutions Institution/University Name of Institution/University General Hospital Celje Number of Employees 1613 Number of Researchers Country Slovenia Postal Adress Oblakova ulica 5 3000 Celje Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +386 3 423 3000 Fax +386 3 423 3666 Website www.sb-celje.si Research Team Objectives Main Fields Partners/Interests R.Komadina Medical sciences / Neurobiology, Gerontologic trauma, major trauma http://sicris.izum.si/search/rsr.aspx?opt=3&lang=eng&id=11437 Project: Trauma Register Acronym: L3-2037 (C) Duration: 1.1.2000 - 31.12.2001 Keywords: scoring systems, registry, multiple injured patients Project: Genetic factors and hormones in metabolic diseases Acronym: J3-3314 (C) Duration: 1.7.2001 - 30.6.2004 RANGE: 0,63 FTE and 417 unpaid hours Keywords: osteoporosis, arthroplasty, diabetic nephropathy, insulin resistance Project: Telederm - Modern diagnostic of skin tumour and selected dermathoses Acronym: L3-3426 (C) Duration: 1.7.2001 - 30.6.2004 Keywords: Skin tumours, Dermatosis, Internet, Diagnostics Institutions Institution/University Name of Institution/University General Hospital Slovenj Gradec Number of Employees Number of Researchers Country Slovenia Postal Adress Gosposvetska 1 2380 Slovenj Gradec Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +386 2 8823400 Fax +386 2 8823411 Website http://www.sb-sg.si/ Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital “Dubrava” Number of Employees Number of Researchers Country Croatia Postal Adress Avenija Gojka Šuška 6 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 2902444 Fax +385 1 2860259 Website http://www.kbd.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital “Šibenik” Number of Employees Number of Researchers Country Croatia Postal Adress Stjepana Radića 83 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 22 246246 Fax +385 22 214707 Website http://www.bolnica-sibenik.htnet.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital for Infectious Diseases “Dr. Fran Mihaljević” Number of Employees Number of Researchers Country Croatia Postal Adress Mirogojska 8 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 4603222 Fax +385 1 4678235 Website http://www.bfm.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital for Psychiatry “Vrape” Number of Employees Number of Researchers Country Croatia Postal Adress Bolnička c.32 10090 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 3780666 Fax +385 1 3483660 Website http://www. bolnica-vrapce.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Clinical Hospital for Pulmonary Diseases “Jordanovac” Number of Employees Number of Researchers Country Croatia Postal Adress Jordanovac 104 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 2385100 Fax +385 1 213045 Website http://jagor.srce.hr/jordanovac Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Croatian Academy of Sciences and Arts Number of Employees Number of Researchers Country Croatia Postal Adress Zrinski trg 11 10000 Zagreb Projects Domestic Projects 3 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4895111 Fax +385 1 4819979 Website http://www.hazu.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Croatian Academy of Sciences and Arts – Cabinet for the Research and Standardization of Immunological Substances Number of Employees Number of Researchers Country Croatia Postal Adress Demetrova 18 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 443586 Fax Website http://mahazu.hazu.hr/ENG/Cab_ResSt_ImmS.html Research Team Objectives Main Fields immunologically active substances in viral precancerous, cancerous, and other diseases Partners/Interests Institutions Institution/University Name of Institution/University Croatian Academy of Sciences and Arts – Cabinet for the Research of the Structure and Function of the Sensory Organs Number of Employees Number of Researchers Country Croatia Postal Adress Ante Kovačića 5 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 4698246 Fax +385 1 4856211 Website http://mahazu.hazu.hr/ENG/Cab_ResS-F_Sen-O.html Research Team Objectives Main Fields sensory neuropsychology Partners/Interests Institutions Institution/University Name of Institution/University Croatian Academy of Sciences and Arts – Department of Medical Sciences Number of Employees Number of Researchers Country Croatia Postal Adress Andrije Hebranga 1 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 4895171 Fax +385 1 4819979 Website http://www.hazu.hr/Raz4.html Research Team Objectives Main Fields professional health hazards, oncogenic and growth factors, tumors, occupational medicine and medical ecology, animal and comparative pathology, allergology and clinical immunology, biological substances, drugs, cardiovascular diseases, subcellular pathology, atherosclerosis, parodontal diseases, and biomedical ethics Partners/Interests Institutions Institution/University Name of Institution/University Faculty of Kinesiology of the University of Zagreb Number of Employees Number of Researchers Country Croatia Postal Adress Horvaćanski zavoj 15 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 3658666 Fax +385 1 3634146 Website http://www.kif.hr Research Team Objectives Main Fields kinesiology Partners/Interests Institutions Institution/University Name of Institution/University Faculty of Medicine of the University of Split Number of Employees Number of Researchers Country Croatia Postal Adress Šoltanska 2 21000 Split Projects Domestic Projects 16 International Projects Contact Person Name Email [email protected] Function Phone +385 21 557900 Fax +385 21 557625 Website http://www.mefst.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Faculty of Science of the University of Zagreb Number of Employees Number of Researchers Country Croatia Postal Adress Horvatovac 102A 10000 Zagreb Projects Domestic Projects 3 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4606010 Fax +385 1 4606013 Website http://www.pmf.hr Research Team Objectives Main Fields biology, physics, chemistry, mathematics ,geophysics, geography, geology Partners/Interests Institutions Institution/University Name of Institution/University Health Polytechnic in Zagreb Number of Employees Number of Researchers Country Croatia Postal Adress Mlinarska 38, p.o. box 901 10000 Zagreb Projects Domestic Projects 1 International Projects Contact Person Name Email [email protected] Function Phone +385 1 4669750 Fax +385 1 4668080 Website http://www.zvu.hr Research Team Objectives Main Fields Partners/Interests Institutions Institution/University Name of Institution/University Institute for Anthropological Research Number of Employees Number of Researchers Country Croatia Postal Adress Amruševa 8, p.o. box 290 10000 Zagreb Projects Domestic Projects International Projects Contact Person Name Email [email protected] Function Phone +385 1 4816903 Fax +385 1 4813777 Website http://www.pmf.hr Research Team Objectives Main Fields anthropology, mathematical modelling and biostatistics, human ecology, population genetics, ergonomics, anthropological biometrics, biomechanics, occupational medicine, anthropological anatomy, epidemiology, health prevention, social medicine, forensics, archaeology, anthropogeographics, general ecology Partners/Interests Individual Researchers and Teams Anaesthesiology Research Team Research Team Name ICU Individual Researcher No Research Team Leader Name Prof. Bruno Barsic Research Team Members Team Member 0 dr Igor Klinar [] Team Member 1 dr Dragan Lepur [] Team Member 2 dr Marija Santini [] Team Member 3 dr Vladimir Krajinovic [] Team Member 4 dr Marko Kutlesa [] Contact Person Name Prof. Bruno Barsic Email [email protected] Function hread of the ICU Phone 00385-1-4603404 Fax 00385-1-4603255 Website http://tkojetko.irb.hr/znanstvenikDetalji.php?sifznan=2888 Research Team Objectives Main Fields Anaesthesiology Therapeutics Internal Medicine infectious endocarditis - outcome, risk factors, echocardiography, treatment sepsis - pathogenesis, appropriate treatment, blood stream infections in elderly severe pneumonia - outcome, mechanical ventIlation, antimicrobial treatment, therapeutic response nosocomial infections - incidence, NI in elderly ICU patients antimicrobial therapy - evaluation of response in severe patients, timing central nervous system infections - outcome, treatment endocarditis - outcome, treatment, central nervous system complications pneumonia - outcome, mechanical ventilation, Partners/Interests researcher Anaesthesiology Internal Medicine intensivist, interested in antimicrobial treatment, availability to measure respiratory parameters in mechanically ventilated patients Outcome of mechanically ventilated patients with severe community-acquired pneumonia Evaluation of therapeutic response Institution/University Name of Institution/University Hospital for Infectious Diseases Number of Employees 550 Number of Researchers 25 Country Croatia Postal Adress mirogojska 8 10000 Zagreb Anatomy Research Team Research Team Name Center for Bone Morphology Individual Researcher Yes Research Team Leader Name Professor Ana Marusic Research Team Members Team Member 0 Resarch Assistant Katerina Zrinski Petrovic [[email protected]] Team Member 1 Doctoral Fellow Ana Vujaklija [[email protected]] Team Member 2 Research Assistant Sanja Ivcevic [[email protected]] Team Member 3 Doctoral Fellow Anita Lukic [[email protected]] Team Member 4 Doctoral Fellow Mihael Rudeš [[email protected]] Team Member 5 Doctoral Fellow Daniela Salopek [[email protected]] Team Member 6 Postdoctoral Fellow Natasa Kovacic [[email protected]] Team Member 7 Postdoctoral Fellow Ivan Kresimir Lukic [[email protected]] Team Member 8 Assistant Professor Vedran Katavic [[email protected]] Team Member 9 Assistant Professor Danka Grcevic [[email protected]] Research Team Projects Project Name Interactions Between Bone and the Immune System: A Role for Fas-mediated Apoptosis Project Leader Professor Ana Marusic [[email protected]] Project Funding Agency Wellcome Trust Project Budget 200000 € Project Start Date 2004-04-01 Project End Date 2007-04-01 Project Partners Professor Peter Croucher, UK, University of Sheffield, Medical School, Bone Biology Group Project Summary The bone and the immune systems are developmentally and functionally related. Abnormal regulation of these systems can lead to the development of disorders characterised by increased bone loss, including osteoporosis. An important determinant of bone loss is the balance between osteoclastic bone resorption and bone formation by osteoblasts. One process that can regulate this balance is apoptosis. Although apoptosis has been established as an important regulator of normal and pathological bone turnover, the molecular mechanisms mediating apoptosis in bone cells are not well understood. Cells of the immune system are ideally placed to contribute to this process. They can be found closely associated with the cells of bone and they also express molecules know to induce apoptosis. One family of molecules that may play a critical role is the tumour necrosis factor family. One member of this family, Fas-ligand (FasL), a trimeric type II membrane protein that binds to its receptor, Fas, induces apoptosis in target cells. The role of this system in bone is poorly understood. Osteoblasts may express Fas and undergo FasL mediated apoptosis in vitro, although the effect on osteoclasts is less clear. In preliminary studies we have demonstrated that mice with a mutation in the gene encoding FasL (gld, generalized lymphoproliferative disorder mice) have increased bone mineral density. This is the result of an intrinsic disturbance in osteoblast apoptosis, as well as increased production of osteoprotegerin, a TNF receptor family member responsible for inhibiting osteoclastic bone resorption. The aim of the proposed study is to establish the role of FasL in regulating bone cell apoptosis. These will include establishing a. whether osteoblasts and osteoclasts express Fas and FasL, b. whether FasL can induced apoptosis of osteoblasts and osteoclasts, c. whether immune cells can promote bone cell apoptosis and whether this is mediated by FasL, d. whether gld mice have abnormalities in bone formation, e. whether Fas-ko mice, which have a gene deletion for Fas, also have increased bone density, f. whether FasL regulates osteoblast and osteoclast apoptosis in vivo. These studies will improve our understanding of the role of Fas/FasL in bone and their role in bone cell apoptosis. This may lead to the identification of new therapeutic targets for regulating bone mass. Project Website www.wellcome.ac.uk/ Anatomy Research Team Projects Project Name Molecular interrelations between bone and immune system Project Leader Professor Ana Marusic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-08-01 Project End Date 2005-05-31 Project Partners Project Summary Close interdependence of the bone and immune system is well known, but their cellular and molecular interactions in vivo have been poorly defined. Published reports give contradictory results on the role of immune cells in bone metabolism in vivo, but also call for an integrative approach to both systems. To test the hypothesis that immune cells are involved in the regulation of bone metabolism in vivo and vice versa, the proposed research will investigate the bone phenotype of transgenic and mutant mice with disturbances in the immune system, as well as indicators of bone metabolism in human counterparts of experimental immunodeficiencies. The research will focus on the mice with generalized lymphoproliferative disorder, which have a mutation in the Fas/Fas ligand apoptotic system (gld and lpr mutation and Fas gene knockout). The bone phenotype will be assessed by bone densitometry, microCT and classical histomorphometry, and the immunological phenotype by flow citometry and sorting. We will assess bone metabolism in vivo in three experimental models: 1) endochondral osteoinduction by BMP-2, 2) bone marrow ablation, and 3) ovariectomy-induced estrogen depletion. The activity of bone cells in these models will be monitored at the tissue, cellular and gene expression levels for cytokines and bone-specific molecules, using the tools of flow cytometry and sorting, ex vivo culture, and quantitation of gene expression. Interdependence of bone and immune systems in these mice will be investigated in bone marrow transfer experiments, where we will characterize the bone and immune phenotype of the generated chimeras. Three mutant/transgenic mouse lines will be used (gld and lpr mutation and Fas gene knockout) to validate the observed phenomena and investigated if different components of the Fas system have different roles in regulation of bone metabolism. In parallel, we will investigate bone metabolism in the human counterpart of the gld/lpr disorder, Sjoegren’s syndrome. The experiments outlined in the project proposal should contribute to the understanding of interactions between the bone and immune system and proved a unified approach to the two systems. The results of the research would particularly contribute to better understanding and possible therapeutic interventions in different immunological and hematological disorders. Project Website www.mef.hr Research Team Projects Project Name Development of a diagnostic procedure of quantitative PCR for measuring cytokines in small samples Project Leader Professor Ana Marusic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2004-05-01 Project End Date 2006-04-30 Project Partners The aim of the project is precommercial development of a diagnostic test for detecting the expression of cytokines in small samples, using the quantitative PCR. Project Website www.mef.hr Contact Person Name Professor Ana Marusic Email [email protected] Function Professor of Anatomy; Editor in Chief, Croatian Medical Journal Phone 38514566846 Anatomy Fax 38514590222 Website www.cmj.hr Research Team Objectives Main Fields Anatomy Biology Immunology and Immunohaematology The research group from the Laboratory for Molecular Immunology at the Zagreb University School of Medicine studies bone phenotype in different disturbances of the immune system. Bone and immune system have not only a close anatomical but also very important functional relationship, sharing the same cell precursors and regulatory cytokines. In our work we use in vivo models because the threedimensional nature of the cells interactions is only preserved in vivo. This we accomplish by studying static and dynamic bone morphometry, thus assessing the volume of trabecular bone and the rate of new bone apposition on the bone surfaces. Our laboratory is equipped with a light and fluorescence microscope coupled to the Osteomeasure, specific histomorphometry software for bone morphometry according to current standards. To study the cellular and molecular mechanism of cellular interactions in the bone-bone marrow environment, we can isolate specific bone cell precursors and grow them ex vivo. Cell development and function is assessed at several levels: 1) by classical histology (staining of osteoblasts by alkaline phosphatase activity, staining of osteoclast for acid phosphatase activity and assesing activitiy by resorption of bone mineral in vitro), 2) immunohistochemistry, 3) flow cytometry of both bone and immune cells, 4) gene expression at the level of mRNA (quantitative PCR), 5) gene expression at the protein level (Western blot and ELISA). As the full developmental potential of bone cells and their interactions are possible only in vivo, we alos use in vivo experimental models which replicate bone differentiation during embryonic and fetal development: 1) new bone induction at extra skeletal sites by recombinant bone morphogenetic protein-2, which reproduces endochondral bone development, and 2) osteogenic reparation after mechanical bone ablation, which reproduces membranous bone development without a cartilaginous intermediate. As bone cells are sensitive to radiation, classical experiments with bone marrow transplantation and creation of allogeneic chimeras is not a good experimental model to study interactions between the bone and bone marrow cells, so we have developed the parabiotic model in which joint circulation of blood cells may affect the bone system. Partners/Interests researcher industrial partner Anatomy Biology Immunology and Immunohaematology generation and analysis of transgenic mice, particularly the bone and immune phenotype characterisation of bone phenotypes of transgenic mice, specifically with disturbances in the immune system Institution/University Name of Institution/University Zagreb University Sof Medicine Number of Employees 600 Number of Researchers 400 Country Croatia Postal Adress Salata 3 10000 Zagreb Anatomy Research Team Research Team Name reproductive biology group Individual Researcher No Research Team Leader Name Prof. Dr. Davor Jezek Research Team Members Team Member 0 M.D. Gordan Grahovac [[email protected]] Team Member 1 M.Sc., Ph.D. Sanja Vujisic [[email protected]] Team Member 2 M.Sc. Feodora Stipoljev [[email protected]] Team Member 3 Prof. Dr. Ruzica Pezerovic-Panijan [[email protected]] Team Member 4 M.D. Berivoj Miskovic [[email protected]] Team Member 5 Prof. Dr. Visnja Milavec-Puretic [[email protected]] Team Member 6 Prof. Dr. Marina Kos [[email protected]] Team Member 7 M.D., M. Sc. Duska Markov-Glavas [[email protected]] Team Member 8 Prof. Dr. Gordana Juric-Lekic [[email protected]] Team Member 9 Prof. Dr. Miro Kasum [[email protected]] Team Member 10 Prof. Dr. Grbesa Djurdjica [[email protected]] Team Member 11 M.D., M. Sc. Trpimir Goluza [[email protected]] Team Member 12 Ph.D. Ozren Gamulin [[email protected]] Team Member 13 M.D. Romana Dmitrovic [[email protected]] Team Member 14 M.D., Ph.D. Ervina Bilic [[email protected]] Team Member 15 M.D., Ph.D. Ernest Bilic [[email protected]] Team Member 16 M.D., Ph.D. Tomislav Banek [[email protected]] Team Member 17 Prof. Dr. Ljerka Banek [[email protected]] Team Member 18 M. Sc. Maja Balarin [[email protected]] Research Team Projects Project Name Investigations on the male sex gland Project Leader Prof. Dr. Davor Jezek [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-07-01 Project End Date 2006-07-01 Project Partners Germany/University of Hamburg/Dept. of Andrology; Austria/University of Innsbruck/Dept. of Pathology; Slovenia/University of Ljubljana/Veterinary Faculty Project Summary The human testis is composed of seminiferous tubules and the interstitial tissue. Within the interstitial tissue, numerous macrophages, Leydig (interstitial) cells and blood vessels are situated. Recent investigations on the morphology and histophysiology of the rodent testis demonstrated specific cellular junctions between macrophages and Leydig cells. Macrophages influence steroidogenesis and testosterone production in Leydig cells via paracrine factors (i.e. lipophilic factor 25hydroxycholesterol, interleukins 1 and 6 and tumour necrosis factor alpha /TNF-alpha/). In addition, Leydig cells affect neighbouring macrophages by secreting paracrine steroidogenic, proopiomelanocorticoid and other factors. Besides macrophages, interstitial blood vessels influence the testosterone serum levels. These vessels demonstrate rhytmic contractions called "vasomotion", thus changing the absorption of testosterone. AIMS & HYPOTHESIS. The emphasis of the study would be on the development, normal histophysiology and pathology of macrophages, Leydig cells and blood vessels. In patients with non-obstructive azoospermia, an extensive structural change of the testicular interstitial tissue takes place. This change includes an increase in the number of macrophages, distrubance of steroidogenesis within Leydig cells and the consequent pathology of blood vessels. The above mentioned changes of the interstitial tissue would be compared with the status of spermatogenesis in infertile patients. EXPECTED RESULTS. The proposed project would Anatomy reveal new data on the development, normal histophysiology and pathology of macrophages, Leydig cells and blood vessels within the human testis. Moreover, the diagnostic histopathological evaluation of the testicular biopsy would be imporved by: 1. introduction of new markers for macrophages; 2. estimation of the steroidogenesis and testosterone production in Leydig cells; 3. electron-microscopic analysis of the testis interstitial tissue. Parallel comparison of the pathology in the interstitium and within seminiferous tubules (analysis of the preserved number of sperms and late spermatids) would gain prognostic parameters for the therapy of the patients with non-obstructive azoospermia. METHODS: 1. Immunohistochemistry; 2. Electron microscopy; 3. Morphometry (stereology). IMPORTANCE OF THE PROJECT. New data on the testis interstitium and their application in the human reproductive medicine. Project Website Research Team Projects Project Name Histophysiological regulation of human Leydig cells Project Leader Prof. Dr. Davor Jezek [[email protected]] Project Funding Agency Slovenian Agency for Scientific Projects Project Budget 2000 € Project Start Date 2003-01-01 Project End Date 2006-01-01 Project Partners Slovenia/University of Ljubljana/Veterinary Faculty Project Summary Morphological and physiological analyses revealed many differences between sexes beside the primary (sexual glands) and secondary (external sexual characteristics) sexual dimorphisms. Many studies have shown differences between male and female brains, where most differences were described in preoptic area, although some reports also suggest sexual dimorphisms in regions such as hypothalamus and hippocampus. Beside brain, several studies described sex dependent differences in salivary glands. In rodents, there are differences in composition of saliva as well as in the morphology of several salivary glands. Glandula loewenthali was thought to be a part of parotid gland until recently due to vicinity of both glands. However, glandula loewenthali is clearly separated from surrounding tissue. Macroscopically, the gland is dark color and in shape of lens. In rats, sex differences can be observed macroscopically, as gland has bigger volume in males. With aging special cells with many lipid droplets and large amount of smooth endoplasmatic reticulum appear in this gland. Due to their similarity to the cells from harder’s gland they are called harder’s cells. Interestingly, these cells appear only in male rate glandula loewenthali ut not in females. Castration causes reduction in number of this cells while ovariectomy does not affect the gland. Even bigger differences appear in glandula loewenthali at castration of male mice. In mice, both activitiy and amount of acinar cells is reduced after castration, and some acinar tissue is replaced with interstitium. However, in spite of some reports of sexual dimorphisms in this gland in rodents, there are no clear morphological description (especially at electron microscopy level) of these glands in mice and rats, and it is not known the mechanism causing sexual dimorphism. It is not known whether sex dependent differences are completely hormone dependent or are also influenced by genetic background. Steroidogenic factor 1 (SF-1) is a member of nuclear receptor family, essential for normal development and function of endocrine organs. SF-1 knockout mice are born without gonads and adrenals and because gonads in these mice regress several days before steroidogenesis starts, they are never exposed to endogenous steroid hormones. Therefore, SF-1 KO mice represent an excellent and unique model to study sexual differentiation in the absence of steroid hormones. Due to adrenal insufficiency, these mice die few days after birth, but we developed a method of adrenal transplantation that enables us to breed these mice into adulthood. In our laboratory, studies looking for sex differences in behaviors and brain gene expression are already underway. Under current proposal, we would like to extend these studies by examining the influences of hormones and genetic background on sexual dimorphism in salivary glands. Project Website Research Team Projects Project Name Reinke's crystals in healthy and infertile men Project Leader Prof. Dr. Davor Jezek [[email protected]] Project Funding Agency Austrian Ministry of Science and Reasearch Project Budget 2000 € Project Start Date 2006-01-01 Anatomy Project End Date 2007-12-31 Project Partners Austria/University of Vienna/Institute of Materials Physics Project Summary Infertility in men and women has been recognized as a major health problem within the European Union (EU) as well as in the neighbouring European countries. It is estimated that infertility affects 15% of all couples trying to conceive. Epidemiological studies have pointed out that half of infertility problems could be related to the male factor. In many cases (30-70%) the cause for male infertility is not known or not clarified enough (Oehninger, 2001; Sharma et al. 2004). All the above-mentioned data go for the both, Austrian and Croat population. Health systems in Europe are thus confronted with two major problems: the rising number of infertile couples and the rising cost for their treatment. Therefore, it is necessary to reveal factors that contribute to infertility and work out the strategy for the prevention of such health risks. Our project focuses on the male infertility and the role of Reinke's crystals (located in Leydig cells of the male gonad), since these structures are found in normal and infertile adult human testis. Studies on Reinke’s crystals are rare (approx. 20 references in Medline) and their function remains unclear. Of particular interest is comparison of Reinke's crystals in healthy and infertile men with idiopathic non-obstructive azoospermia. Infertile men who have non-obstructive azoospermia (no spermatozoa in their ejaculate) are especially difficult to treat and, therefore, represent population of patients that needs special care and attention of andrologist/urologist and other medical personal (Hauser et al., 1998; Ježek et al., 1998; Amer et al., 2000; Salihu and Aliyu, 2003). Project Website Contact Person Name Prof. Dr. Davor Jezek Email [email protected] Function Associate Professor, Assistant to Dean Phone +38514590251 Fax +38514590251 Website www.mef.hr Research Team Objectives Main Fields Anatomy Cytology Pathology Connective tissue is an important constituent of the male and female reproductive tract. Therefore, the main object of investigation in this survey would be an interstitial tissue of the testis and connective tissue (stroma) of the chorionic villi of the placenta. In addition, the influence of sex glands on some anatomically distant organs and tissues will be investigated. Hypothesis on which the survey is based upon is threefold: a) interstitial compartment of the testis significantly influences the normal development, architecture and function of the whole organ (i.e. testis) as well as the occurrence of the male infertility; b) connective tissue/stroma of the chorionic villi significantly influences the normal development, architecture and function of the whole organ (i.e. placenta) as well as the occurrence of infertility in females (emphasis on the intrauterine growth restriction); c) removal of sex glands (gonadectomy) significantly affects the architecture and function of anatomically distant organs. a) Testis. The aim of this part of the survey would be to get data on the development of macrophages, Leydig cells and blood vessels in the human foetus. In addition, to check if the disturbed architecture and function of these cells/structures contributes to the infertility in man. b) Placenta. The main goal of this part of the project would be to investigate the development and the interaction between so-called Hofbauer cells and blood vessels of the chorionic villi. The normal placentas and placentas form intrauterine growth restriction cases would be compared. c) Sexual dimorphism of the extraorbital lachrymal gland of the rat. This part of the project would deal with the influence of the sex glands (i.e. their removal) on the extraorbital lachrymal gland of the rat. Special emphasis would be given on the changes of the interstitium of the gland. Methods. The following methods will be employed: immunohistochemistry, transmission electron microscopy, transmission electron microscopy with immunogold particles, morphometric (stereological) analysis and molecular biology methods. The expected results would provide valuable data on the development of interstitial tissue of the testis and connective tissue of the chorionic villi. Moreover, the role of macrophages, Leydig cells and blood vessels in the occurrence of infertility in males and females would be elucidated. The assessed data could be very useful in human reproduction. In addition, the role of sex glands in the formation of some tertiary sex characteristics would be clarified. Anatomy Partners/Interests researcher industrial partner Pathology Obstetrics and Gynaecology Public health services multiarray DNA analysis; proteomics, genital infections diagnostics Infertility in South-East Europe Institution/University Name of Institution/University Medical School University of Zagreb Number of Employees 600 Number of Researchers 400 Country Croatia Postal Adress Salata 3b 10000 Zagreb Bacteriology Research Team Research Team Name Chlamydia Individual Researcher No Research Team Leader Name Mr., PhD Radovan Hojs Research Team Members Team Member 0 Mr., PhD Artur Pahor [] Team Member 1 Mr., MD, PhD Ivan Krajnc [] Team Member 2 Mr. MD Aleš Goropevšek [] Team Member 3 Mrs., PhD Avrelija Cencic [] Contact Person Name Mr., PhD Radovan Hojs Email [email protected] Function Head of Department of Medical didactics Phone + 386 2 234 56 01 Fax + 386 2 234 56 00 Website www.f.uni-mb.si Research Team Objectives Main Fields Bacteriology Chlamydia Partners/Interests researcher industrial partner Suitable Bacteriology 1. CHLAMIDIAL INFECTIONS and INFLAMMATION – EXPLOITATION OF THE HOST –EVOLVING TO INFLAMMATORY DISEASES LIKE ATHEROSCLEROSIS, (RHEUMATOID ARTHRITIS AND ASTHMA) Inflammation is now recognised as being pivotal in the pathogenesis of atherosclerosis. Lesions of atherosclerosis consist of blood-borne inflammatory and immune cells that represent important part of atheroma, the remainder being vascular endothelial and smooth muscle cells. They interact with a series of specific cellular and molecular responses that can be described as an inflammatory disease. Cholesterol deposits, found in the arterial wall before any fatty streak-like lesion occurred, can activate complement and initiate cascade that produces powerful chemotactic stimuli for monocytes to enter the forming lesion. Chlamydia(C) pneumoniae is an obligate microbe that commonly causes respiratory infection and is able to infect human smooth muscle cells, arterial endothelial cells and macrophages. It has a unique life cycle – on exposure to a variety of stimuli including antibiotics microbe can convert to a long, inactive intracellular phase in the form of so called cryptic bodies. In this phase Chlamydia is not replicating and is resistant to mode of action of most antibiotics. C pneumoniae contains heat shock protein 60 like sub-units that coud cause inflammatory injury via autoimmune reaction thus indirectly trigger atherogenesis To study early C. pneumoniae infection and infection in correlation with the onset of inflammatory response, we will study the interaction between C. pneumoniae and respiratory tract cells using an in vitro co-culture model. The integrity of a human lung bronchial epithelial (CRL-9482) cell layer and the impact of C. pneumoniae attachment to its status will be determined by measuring transepithelial resistance (TER) and transepithelial potential of the cell monolayer growing on microporous membranes. The translocation of bacteria will be monitored by detection of the microorganisms in media and in macrophages growing in the lower chamber. Cencic group will also study whether IFN-gamma, a proinflammatory cytokine, when added to the basolateral side, will disrupt the tight epithelium and facilitate penetration of C. pneumoniae through the respiratory epithelium. The induction of inflammatory signals in epithelial cells and macrophages (NF-kB, cytokines, iNOS) after C. pneumoniae infection will be determined by ELISA, mRNA-expression arrays and/or RT-PCR. Finally, the cross-talk between C. pneumoniae, lung epithelium and macrophages will be determined to shed light on the early events of infection when C. pneumoniae enters the host respiratory tract. Upon infection, a chlamydial activity protects infected cells against apoptotic stimuli and this could lead to chronic-active and persistent infections during human chlamydial diseases. Häcker group has recently shown that specific degradation of proapoptotic host proteins (so-called BH3-only proteins) is responsible for this activity. Simultaneously, chlamydial infection has a propensity to induce atypical death of the infected cell. At this stage, it is Bacteriology completely unclear which bacterial effector proteins cause the opposing biological effects (inhibition of apoptosis and induction of cell death). However, chlamydial proteins secreted into the cell e.g. via the chlamydial type III secretion system are the most promising candidates. To screen for inhibitors of apoptosis, pooled chlamydial plasmid libraries will be transfected into respiratory epithelial cells. Transfected cells will be subjected to UV-irradiation to induce apoptosis. After 24 h, surviving cells will be harvested, plasmids will be re-isolated, amplified in bacteria and used in a second round of transfection. The procedure will be repeated until cells transfected with individual plasmids can be recovered. Focusing on the bacterial components identified by Hegemann and Subtil groups WP x, expression plasmids will be transfected, and transfected cells will be compared for their UV-resistance with vector-transfected controls. To identify death-inducing proteins, HeLa cells will be transfected with a marker of transfection (GFP) and pools (approximately 20 plasmids) of library samples. When a reduction of GFP-positive cells is seen by flow cytometry, the pools will further be split to identify the active protein. For candidate secreted proteins (identified in WP x), a similar approach will be taken. Upon identification of such chlamydial proteins, their interaction with the host cell’s components and the precise mechanism of their interference with cell death will be defined. The subsequent efforts will be directed at the pharmacological inhibition of these bacterial targets (WP x drug development) and the interference with the corresponding host cell’s targets by RNAi (WP x). Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Biochemistry Research Team Research Team Name Biochemistry Individual Researcher No Research Team Leader Name Mrs., PhD Avrelija Cencic Research Team Members Team Member 0 Mr., PhD Dimitri Komiotis [] Team Member 1 Mr., PhD Costa Antonakis [] Team Member 2 Mr. MD Aleš Goropevšek [] Contact Person Name Mrs., PhD Avrelija Cencic Email [email protected] Function Head of Department of Biochemistry Phone + 386 2 2505 828 Fax + 386 2 23 45 600 Website http://www.mf.uni-mb.si/ Research Team Objectives Main Fields Biochemistry Other allied sciences Partners/Interests researcher industrial partner Suitable Other allied sciences 1. INTERFERONS AND NEWLY SYNTHESISED AMINO-KETONUCLEOSIDES AS ANTIVIRAL AND ANTICANCER AGENTS Interferons (IFNs) are proteins or glycoproteins belonging to a wide family of cytokines. IFNs exert a broad spectrum of biological activities, like elicitation of an "antiviral state" in target cells, that is a transient resistance to infection by numerous viruses, moreover interferons, namely IFN-gamma were shown as strong inhibitors of cancerogenesis and regulator of immunomodulatory activities. Two main types of IFNs have been described, that share no sequence homology : type I IFNs (a, b, t, d, w), include IFNs that are produced mainly in response to a variety of viruses. Type II IFNs include an unique member - IFN-g, produced in adult mammals by activated T lymphocytes and NK cells, that has a multipotential role in immune response. Nucleoside analogues display a wide range of biological activities as anti-tumor, anti-viral and chemotherapeutic agents. In recent years a number of 2´, 3´-unsaturated nucleoside analogues, such as D-2´-3´-didehydro-2´3´-dideoxy-5-fluorocytidine (D-d4FC) and its L-enantiomer (L-Fd4C), have been identified as anti-HIV agents. Cytosine and 5-fluorocytosine derivatives from the L series display potent HBV (EC50 = 0.002 and 0.004 ìÌ, respectively)7 as well as anti-HIV-1 activities without significant cytotoxicity. More recently, the description of the structure-activity relationships of L-3´-fluoro-2´-3´-unsaturated nucleosides, showed potent activity in the cytosine and 5-fluorocytosine derivatives (EC50 = 0.089 and 0.018 ìÌ, respectively). Furthermore, cytosine nucleoside analogues, such as 1-(2-deoxy-2methylene-â-D-erythro-pentofuranosyl) cytosine (DMDC), 2´-deoxy-2´-2´-difluorocytidine (gemcitabine), and 1-(2-C-cyano-2-deoxy-â-D-arabino-pentofuranosyl)cytosine (CNDAC), have been developed as potent antitumor agents, which are effective not only on leukemias and lymphomas, but also on a wide variety of solid tumors in vitro as well as in vivo. It is the purpose of our work to study the potential effects of interferon gamma and newly synthesized nucleoside analogues as potent inhibitors of tumor cells and to try to elucidate the mechanism behind the action. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Biochemistry Research Team Research Team Name Clinic of Dentistry Institute of Biochemistry Individual Researcher No Research Team Leader Name Mr.sci dr.stom. Ana Pejcic Research Team Members Team Member 0 teaching ass Radmila Obradovic [-] Team Member 1 Associate Prof Zoran Pesic [[email protected]] Team Member 2 teaching ass Aleksandar Petrovic [-] Team Member 3 associate Prof Tatjana Cvetkovic [[email protected]] Team Member 4 Professor Ljiljana Kesic [-] Team Member 5 Associate Prof Jelenka Nikolic [[email protected]] Team Member 6 Professor Vesna Zivkovic [[email protected]] Team Member 7 teaching ass Ana Pejcic [[email protected]] Team Member 8 Professor Branislava Mirkovic [[email protected]] Team Member 9 Professor Draginja Kojovic [-] Contact Person Name Mr.sci dr.stom. Ana Pejcic Email [email protected] Function Phone 9938118512500 Fax Website Research Team Objectives Main Fields Biochemistry Dentristry biochemical investigation of gingival fluid, enzymes and saliva immunohistochemical investigation of gingival inflammation with MIB-1, Ki67 antigen, p27, p21 and p53 Partners/Interests researcher Biochemistry Dentristry Other allied sciences researchers of biochemical science researchers of pathological science researchers of periodontal disease Periodontal disease is a major problem for the oral health worker. It is the result of the accumulation of dental plaque at the marginal gingivae leading to inflammation of the periodontal tissues. Periodontal disease is prevalent in most human population and results in significant morbidity, with premature tooth loss in severely affected individuals. Much research has been carried out into the epidemiology, aetiology, prevention, and clinical management of perioontal disease, and this has resulted in a significant increase in our understanding of the condition. Chronic periodontitis is defined as plaque-induced inflammation of the periodontal tissues which has resulte in destruction of the periodontal ligament, loss of crestal alveolar bone, and apical migration of the epithelial attachment. Bacterial plaque is the primary aetiological actor in periodontal disease and the disease will not occur in the absence of plaque. Most local secondary factors are mechanical plaque traps, promoting plaque accumulation at specific sites. Periodontal disease is result of the interaction of bacteria and the factors derived from plaque with the host tissues. The destructive and protective mechanisms which operate in periodontal disease are normally considered to be in equilibrium, resulting in a stable or quiescent lesion. Bursts of periodontal breakdown may occur when this balance is upet, either because of an increase in destructive factors, or because of a decrease in the effectiveness of protective mechanisms. The ability to identify the mechanisms likely to result in periodontal breakdown might have important clinical implicatins. Firstly, it might be possibleto identify and target high risk groups of patients for special care and management, and, secondly, it might be possible to determine more accurately the efficacy of treatment procedures. The reasons for the occurrence of periodontal destruction, the factors which may determine disease susceptibility, and the reasons for Biochemistry disase progression at different sites in the same patient are some of the most important questions in periodontology today. Before discussing the processes and mechanisms involved in periodontal disease, it is important to establish a sound undestanding of the structure of the normal periodontium. The gingiva provides attachment between the oral mucous memrane and the dental hard tissues and protects the underlying periodontal tissues from invasion by the bacteria present in the oral cavity. In health this is at the amelo-cemental junction, but apical migration of the junctional epithelium occurs in disease. Oral epithelium is stratified squamous epithelium and, like other similar epithelia, is composed of keratinocytes and non-keratinocytes or clear cells. Cell devision normally occurs only in the basal cell layet and the cells which arise from these divisions move graduallythrough the epithelium towards the surface, where they are shed. These changes are accompanied by the synthesis of a number of cell products, the most conspicuous of which is keratin, which packs the cells in the keratinized layer and contributes to the mechanical toughness of the superficial layers. This process of maturation is termed differentation. The non-keratinocyte population of epithelium comprises melanocytes, lymphocytes, Langerhans cells, and Melker cells. The keratinocytes in oral epithelium are continually shed from the surface, and in health these are replaced by an equal number of successors arising from cell division in the basal cell layers. Epithelial turnover is influenced by factors which affect the rate of cell division, the maturation and movement of cells through the prickle cell layers, and the rate of desquamation. Keratinocytes in the prickle cell layer producecd substances called cytokines. These are proteins or glycoproteins which are produced by a variety of cell types and which regulate the growth and differentationb of other cells. Cytokines usually act localy, although some have a systemic action. Epithelial turnover appears to be affected by at least three cytokines: epidermal growth factor (EGF), transforming growth factor alpha (TGFÜ), and transforming growth factor beta(TGFâ). The process of re-epitelization that leads to healing of oral mucosal wounds results from a carefully orchestrated proliferation and migration of epithelial cells. Cell migration occurs through a combination of basal cell migration and sliding of the epithelial cell mass above the migrating basal cells. Cellular proliferation is a fundamental biological process coordinating with other processes, tissues homeostasis and repair, require stringent control. The ideas of this projects are: • To elucidate the molecular basis of the lack of cellular proliferation in the migrating epithelial gingivae during the re-epithelization of oral mucosal wounds; • To elucidate the expression of cell-cycle regulators critical for G1-phase progression and S-phase analysed immunohistochemically; • To compare normal human mucosa across gingival epithelia migrating with marker Ki67; • To study cell kinetics of gingival, sulcular and junctional epithelia in periodontitis; • To investigate expression of p21 and possible correlation between this parameter and clinicopathologic features, p53 accumulation and the proliferation-associated marker Ki67; • To investigate the effects of lipopolysaharides on keratinocyte growth factor (KGF) and expression levels of KGF in normal and inflamed gingival tissue. Institution/University Name of Institution/University Medical Faculty - group for dentistry Number of Employees 154 Number of Researchers 25 Country Serbia and Montenegro Postal Adress Bld. Z. Djindjica 81 18000 Nis Biochemistry Research Team Research Team Name Department for Molecular Biology Individual Researcher No Research Team Leader Name Dr Goran Poznanovic Research Team Members Team Member 0 Sci. Consultant Miodrag Petrovic [[email protected]] Team Member 1 Sci. Consultant Goran Poznanovic [[email protected]] Team Member 2 Res. Assistant Aleksandra Uskokovic [[email protected]] Team Member 3 Res. Scientist Melita Vidakovic [[email protected]] Team Member 4 Res. Scientist Mirjana Mihailovic [[email protected]] Team Member 5 Sci. Consultant Svetlana Ivanovic-Matic [[email protected]] Team Member 6 Res. Scientist Vesna Martinovic [[email protected]] Team Member 7 Sr. Res. Scientist Ilijana Grigorov [[email protected]] Team Member 8 Res. Assistant Nevena Grdovic [[email protected]] Team Member 9 Res. Scientist Svetlana Dinic [[email protected]] Team Member 10 Sci. Consultant Desanka Bogojevic [[email protected]] Team Member 11 Jr. Res. Assistant Jelena Arambasic [[email protected]] Research Team Projects Project Name Acute and chronic stress: homeostaic regulatory mechanisms in the acute radiation syndrome and diabetes Project Leader Science Consultant Goran Poznanovic [[email protected]] Project Funding Agency Min. Sci. Environ. Protect. Rep. Serbia Project Budget 97180 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners (Project realized in: Serbia / Institute for Biological Research / Department of Molecular Biology) Project Summary Examiniation of the adaptive mechanisms to acute homeostatic challenges after exposure of the rat to (i) ionizing radiation and (ii) during a sustained homeostatic disturbance in streptozotocin-induced diabetes. The project is focused on (i) the acute-phase (AP) proteins: alpha1-acid glycoprotein (AGP), alpha2-macroglobulin (MG) and haptoglobin (Hp), circulatory proteins whose synthesis increase significantly during the AP response, an essential manifestation of the adaptive process, and on (ii) the mechanisms that regulate poly(ADP-ribosyl) polymerase (PARP-1) activity in homeostatic processes that are executed in response to oxidant stress during the acute radiation syndrome (ARS) and prolonged inflammation during diabetes. Work on the project is expected to (i) elucidate the control of the AP response in ARS and diabetes by characterizing the molecular signals and molecular regulators of AP protein gene transcription, (ii) establish the potential protective roles of the individual AP proteins during the ARS and diabetes, and to (iii) clarify the molecular mechanisms that control PARP-1 activity as a precondition of the second phase of research that would examine the molecular events in the cell after PARP-1 inhibition. This is of particular importance in light of the presumed role that PARP-1 inhibitors have in therapy of the pathophysiological changes occurring in diabetes and other types of inflammation. Project Website Project Name Acute and chronic stress: homeostaic regulatory mechanisms in the acute radiation syndrome and diabetes Project Leader Science Consultant Goran Poznanovic [[email protected]] Project Funding Agency Min. Sci. Environ. Protect. Rep. Serbia Project Budget 97180 € Project Start Date 2006-01-01 Biochemistry Project End Date 2010-12-31 Project Partners (Project realized in: Serbia / Institute for Biological Research / Department of Molecular Biology) Project Summary Examiniation of the adaptive mechanisms to acute homeostatic challenges after exposure of the rat to (i) ionizing radiation and (ii) during a sustained homeostatic disturbance in streptozotocin-induced diabetes. The project is focused on (i) the acute-phase (AP) proteins: alpha1-acid glycoprotein (AGP), alpha2-macroglobulin (MG) and haptoglobin (Hp), circulatory proteins whose synthesis increase significantly during the AP response, an essential manifestation of the adaptive process, and on (ii) the mechanisms that regulate poly(ADP-ribosyl) polymerase (PARP-1) activity in homeostatic processes that are executed in response to oxidant stress during the acute radiation syndrome (ARS) and prolonged inflammation during diabetes. Work on the project is expected to (i) elucidate the control of the AP response in ARS and diabetes by characterizing the molecular signals and molecular regulators of AP protein gene transcription, (ii) establish the potential protective roles of the individual AP proteins during the ARS and diabetes, and to (iii) clarify the molecular mechanisms that control PARP-1 activity as a precondition of the second phase of research that would examine the molecular events in the cell after PARP-1 inhibition. This is of particular importance in light of the presumed role that PARP-1 inhibitors have in therapy of the pathophysiological changes occurring in diabetes and other types of inflammation. Project Website Contact Person Name Dr Goran Poznanovic Email [email protected] Function Science Consultant Phone +381.11.2078342 Fax +381.11.2761433 Website http://www.ibiss.bg.ac.yu/ Research Team Objectives Main Fields Biochemistry Biology Physiology Acute and chronic stress: homeostaic regulatory mechanisms in the acute radiation syndrome and diabetes. Examination of the adaptive mechanisms to acute homeostatic challenges after exposure of the rat to ionizing radiation and during a sustained homeostatic disturbance in streptozotocin-induced diabetes. The project is focused on (i) the acute-phase (AP) proteins: alpha1-acid glycoprotein (AGP), alpha2-macroglobulin (MG) and haptoglobin (Hp), circulatory proteins whose synthesis increase significantly during the AP response, an essential manifestation of the adaptive process, and on (ii) the mechanisms that regulate poly(ADP-ribosyl) polymerase (PARP-1) activity in homeostatic processes that are executed in response to oxidant stress during the acute radiation syndrome (ARS) and prolonged inflammation during diabetes. Work on the project is expected to (i) elucidate the control of the AP response in ARS and diabetes by characterizing the molecular signals and molecular regulators of AP protein gene transcription, (ii) establish the potential protective roles of the individual AP proteins during the ARS and diabetes, and to (iii) clarify the molecular mechanisms that control PARP-1 activity as a precondition of the second phase of research that would examine the molecular events in the cell after PARP-1 inhibition. In the first stage of research the mechanisms of regulation of PARP-1 functioning under basal conditions, during DNA repair, apoptosis and necrosis will be studied by examining the dynamic interactions of PARP-1 with the nuclear matrix, its potential protein binding partners (A/C lamins, transcription factor NF-kB that plays a key role in the inducible expression of genes mediating proinflammatory effects), and matrix association regions on DNA. The research is expected to extend to the examination of the molecular events in the aftermath of PARP-1 inhibition. Partners/Interests researcher Biology Biochemistry Physiology Established primary cardiocyte cell culture, molecular biological and cytological methods of characterization of different types of cell death. Proteomics. Initial degradation of chromatin into high-molecular weight DNA fragments during apoptosis reflects Biochemistry the periodicity of chromatin organization into nuclear matrix-attached loops. In the paper: Grdović, N. & Poznanović, G.: Characterization of an Mg2+-dependent endonucleolytic activity of the rat hepatocyte nuclear matrix. Comp. Biochem. Physiol. Part B. (2003) 136:495-504, we put forward the hypothesis that this pattern of DNA cleavage is also a result of the localization of an endonuclease on the nuclear matrix. Namely, we observed an endonucleolytic activity of the isolated rat hepatocyte nuclear matrix. It was Mg2+-dependent, with an optimal activity at pH 7.2 in the absence of either Na+ or K+. It was fully active in the presence of Zn2+ and capable of introducing single-strand breaks into plasmid DNA. It did not display a sequence-specific activity. A 23 kD DNA nuclease that was principally localized on the rat hepatocyte nuclear matrix was detected. The enzyme shared the biochemical requirements with the nuclear matrix endonucleolytic activity, thus we proposed that p23 could be responsible for the endonucleolytic activity of the nuclear matrix. In view of its properties and preferential localization on the nuclear matrix, the endonuclease described herein could be a possible candidate that brings about initial DNA cleavage during apoptosis. To investigate the nature of the interaction of p23 with the nuclear matrix, the nuclear matrix was prepared using different procedures and examined for the presence/absence of the enzyme by activity gel analysis. Treatment of isolated nuclei with sodium tetrathionate (NaTT), a sulfhydryl-cross-linking agent, led to the complete recovery of p23 in the nuclear matrix, whereas incubation of nuclei with dithithreitol (DTT), a sulfhydryl-reducing agent, led to its complete solubilization and resulting absence from the nuclear matrix. Exposure of the isolated nuclear matrix to DTT in high-ionic strength buffer, a procedure that promotes the solubilization of the internal nuclear matrix, caused the nearly complete solubilization of p23. It was concluded that disulfide bonds play an essential role in the association of p23 with the nuclear matrix and that p23 is mostly localized in the nuclear matrix interior. (Grdović, N., Vidaković, M. & Poznanović, G. Binding of a 23 kD endonuclease to the rat liver nuclear matrix. (2005) Gen. Physiol. Biophys. 24: 99-111). Diabetes is associated with persistent oxidative stress which eventually leads to the development of diabetic endothelial and myocardial dysfunction. The pathomechanism envisions that the reactive oxyradicals that are persistently generated in the diabetic state cause considerable DNA strand breakage. The subsequent activation of cellular DNA repair processes leads to PARP-1 overactivity; the concomitant ATP and NAD+ consumption results in a cytotoxic failure of energy metabolism that leads to cardiomyocyte death that promotes the development of cardiomyopathy. Recently, we established the presence of significant p23 activity in nuclear matrices prepared from cardiocyte nuclei that were isolated from control rats and from rats during streptozotocin-induced diabetes. We wish to characterize the role of the nuclear matrixassociated endonuclease p23 in the signaling pathway(s) in oxyradical-induced cardiomyocyte death during streptozotocin-induced diabetes. Institution/University Name of Institution/University Institute for Biological Research Number of Employees 212 Number of Researchers 179 Country Serbia and Montenegro Postal Adress Despot Stephen Boulevard 142 11060 Belgrade Biochemistry Research Team Research Team Name Department of Biochemistry Individual Researcher No Research Team Leader Name PhD Anita Markotic Research Team Members Team Member 0 assistant professor Irena Drmic Hofman [] Team Member 1 assistant Vedrana Cikes Culic [[email protected]] Team Member 2 assistant professor Anita Markotić [[email protected]] Team Member 3 Professor Maja Pavela-Vrancic [] Team Member 4 BSc Sandra Dujic Bilusic [] Research Team Projects Project Name Optimization of factors that influnce liver regeneration Project Leader Assistant Professor Anita Markotic [[email protected]] Project Funding Agency Ministry of Science, Edication and Sports CRO Project Budget 25000.00 € Project Start Date 2001-12-14 Project End Date 2003-12-14 Project Partners Germany/University of Muenster/Institute for Medical Physics and Biophysics Project Summary The aim of the project was to find optimal protocol of hyperbaric oxygenation (HBO) on rat liver. Rats were sacrificed 54 h after 15% hepatectomy, liver and body weights were measured, and serum alanine transaminase (ALT) and aspartate transaminase (AST) activity and albumin levels were determined. The lipid peroxide level, as indicated by malondialdehyde production in the remnant liver was measured, and liver sections were analyzed by light microscopy. Five groups of 10 rats in each group were studied. The preHBO and pre-hyperbaric pressure (preHB) groups were treated before partial hepatectomy with 100% O2 and 21% O2, respectively, at 202,650 pascals, daily for 3 days (45 min/ day). The control group was not treated before partial hepatectomy and recovered under normal ambient conditions after the procedure. Groups postHBO and postHB were treated after partial hepatectomy with HBO and HB, respectively, three times (45 min/day). The preHBO group presented a significant increase in the initiation of the regeneration process of the liver 54 h postoperatively. The liver/body weight ratio was 0.0618 ± 0.0084 in the preHBO compared to 0.0517 ± 0016 g/g in the control animals (P = 0.016). In addition, the preHBO group showed significant better liver function (evaluated by the lowest serum ALT and AST activities, P = 0.002 and P = 0.008, respectively) and showed a significant decrease in serum albumin levels compared to control (P < 0.001). Liver lipid peroxide concentration was lowest in the preHBO group (P < 0.001 vs control and postHBO group) and light microscopy revealed that the composition of liver lobules in the preHBO group was the closest to normal histological features. These results suggest that HBO pretreatment was beneficial for rat liver regeneration after partial hepatectomy. Project Website www.mefst.hr Project Name Expression of glycosphingolipids in regenerated rat liver Project Leader Assistant Professor Anita Markotic [[email protected]] Project Funding Agency Ministry of Science, Edication and Sports CRO Project Budget 17000.00 € Project Start Date 2002-08-22 Project End Date 2006-05-31 Project Partners Germany/University of Muenster/Institute for Medical Physics and Biophysics Project Summary Gangliosides from livers of weanling rats were analysed after 15% partial hepatectomy (PH) and different pre- and post-operative hyberbaric oxygenation (pre- and postHBO). Neu5Ac was the predominant ganglioside-derived sialic acid (>85%) compared to Neu5Gc. Almost identical low total sialic acid content (Neu5Ac+Neu5Gc) of the control and operated nonHBO animals opposed a 6.4 to Biochemistry 7.6 fold increase in pre- and postHBO animals (69.26 and 81.64 pmol per mg wet weight, respectively). NanoESI-QTOF mass spectrometry combined with HPTLC immunostaining revealed GM3(Neu5Ac) and GM3(Neu5Gc) as major gangliosides, correlating with the respective sialic acid concentrations. Minor neolacto-series gangliosides were enhanced in preHBO and postHBO, but GM1core gangliosides only in preHBO rats. GM2 and GalNAc-GM1b were clearly detectable in oxygenated rats compared to traces in the control and nonHBO animals. These results point at a functional role of gangliosides in liver growth regulation and reconstitution after PH combined with pre- and postoperative HBO treatment. Project Website www.mefst.hr Contact Person Name PhD Anita Markotic Email [email protected] Function assistant professor at Split University Medical School Phone 0038521557938 Fax 0038521557625 Website www.mefst.hr Research Team Objectives Main Fields Biochemistry Genetics Immunology and Immunohaematology 1. Liver regeneration after partial hepatectomy. 2. Glycosphingolipid (GSL)-phenotype in relation to genotype of different leucocyte populations (neutrophiles, monocytes and T lymphocytes) after exercise. 3. GSL expression in relation to genotype in cerebrospinal fluid of children with neurological disorders. Partners/Interests researcher Biochemistry Genetics Immunology and Immunohaematology 1. Ability to work with hepatic cell culture or 2. Flow cytometry 1. Immunohistochemical analyses of glycosphingolipid (GSL) expression in regenerated rat liver. 2. GSL-phenotype and genotype of different leucocyte populations (neutrophiles, monocytes and T lymphocytes) after exercise. 3. GSL-phenotype and genotype of children with neurological disorders. Institution/University Name of Institution/University Split University Medical School Number of Employees 90 Number of Researchers 65 Country Croatia Postal Adress Soltanska 2 21000 Split Biochemistry Research Team Research Team Name Department of Biochemistry - Stress Research Group Individual Researcher No Research Team Leader Name PhD Gordana Matic Research Team Members Team Member 0 BSc Tatjana Perisic [[email protected]] Team Member 1 BSc Ivana Elakovic [[email protected]] Team Member 2 BSc Sanja Manitasevic [[email protected]] Team Member 3 MSc Jelena Brkljacic [[email protected]] Team Member 4 BSc Danijela Vojnovic Milutinovic [[email protected]] Team Member 5 PhD Jadranka Dundjerski [[email protected]] Team Member 6 PhD Gordana Matic [[email protected]] Research Team Projects Project Name Glucocorticoid receptor and heat shock proteins expression and function in pathophysiological states and stress Project Leader PhD Gordana Matic [[email protected]] Project Funding Agency Ministry for Science of Serbia Project Budget 70000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Serbia / University of Belgrade / Faculty of Medicine, Institute of Endocrinology, Diabetes and Metabolic Disease Project Summary Glucocorticoids have a broad array of life sustaining functions and play an important role in the therapy of many diseases. Hence, changes in tissue sensitivity to glucocorticoids, either in the direction of resistance or hypersensitivity, may be associated with and may influence the course and treatment of many pathological states. One of the most important determinants of tissue responsiveness to glucocorticoids is the level and function of the glucocorticoid receptor (GR), an intracellular protein acting as hormone activated transcription factor. The subject of the present research project are molecular mechanisms underlying GR structural and functional modulation. It includes both human and animal studies, in which diverse pathological states and stressful conditions related to changes in tissue sensitivity to glucocorticoids are exploited in order to learn more on the mechanisms regulating GR expression and function. Special attention will be paid on the functional significance of GR interaction with heat shock proteins closely associated with the receptor within multiprotein heterocomplexes. The research along these lines may contribute to better understanding of the biological principles underlying glucocorticoid hormones action and their extensive use as therapeutic means. Project Website www.ibiss.bg.ac.yu/odeljenja/biohemija Project Name Psychobiology of posttraumatic stress disorder Project Leader MD, PhD Eric Vermetten [[email protected]] Project Funding Agency European Commission Project Budget 1300000 € Project Start Date 2004-10-01 Project End Date 2007-09-30 Project Partners Netherlands / University of Utrecht / University Medical Center; Serbia / University of Belgrade / Faculty of Medicine, Institute of Endocrinology Diabetes and Metabolic Disease; Serbia / University of Belgrade / Institute for Biological Research "Sinisa Stankovic"; Serbia / International Aid Network, Belgrade; Italy / University of Bari / Specialization School of Psychiatry; Croatia / University of Rijeka / Medical Faculty, Psychiatric Clinic; United Kingdom / University of London / Queen Mary and Westfield College; Serbia / Biochemistry Military Medical Academy, Belgrade; Serbia / Vinca Institute of Nuclear Sciences, Belgrade. Project Summary Post-traumatic stress disorder (PTSD) is the most common war-related psychiatric disorder occurring among combat veterans and other people exposed to war zone stress. In addition to health problems, this disorder causes numerous long-term socioeconomic damages. Current opinion is that the best results in PTSD understanding, diagnosis and treatment could be achieved by integrating psychological, biological and pharmacotherapeutical approaches. General objective of this project is to better understand the biological basis of psychophysical profiles of PTSD patients. The study will focus on establishing multiple correlations of different PTSD subtypes with relevant psychological, biochemical, endocrinological, genetic, physiological and anthropometric parameters. The psychological and biological studies in this project will be performed on five groups of subjects: a) PTSD patients, b) subjects with PTSD in remission, c) traumatized subjects without PTSD, d) healthy controls from Western Balkans, and e) healthy controls from Western Europe. All subjects in these groups will be male. Additionally, the same psychological studies will be performed on five analogous groups of female subjects. The traumatic experiences of the first three groups (of both genders) are war-related. The main psychological instruments to be used are personality inventories and dissociation questionnaires. Biological measurements will encompass parameters related to hypothalamo-pituitary-adrenocortical axis (including cortisol receptor and its gene polymorphism), anthropometry, body composition, lipid status, insulin resistance, and sleep disturbances. After an advanced statistical analysis of the data, this study will yield new knowledge on relations between: a) basic psychological variables and PTSD, b) biological variables and PTSD, and c) biological and basic psychological variables in health and in PTSD. In addition, the foreseen benefits of the project include: d) development of combined psycho-biological batteries for PTSD screening, diagnosing and risk factors assessing, e) improvement of psychological instruments for measuring PTSD, f) implementation of new biological markers for PTSD, g) recommendation for the improvement of combined psycho- and pharmacotherapy of PTSD. Project Website www.pbptsd.org Contact Person Name PhD Gordana Matic Email [email protected] Function Head of Department/Professor Phone +381 11 2078303; +381 63 8121713 Fax +381 11 2761433 Website www.ibiss.bg.ac.yu/odeljenja/biohemija Research Team Objectives Main Fields Biochemistry Genetics Physiology (1) Molecular mechanisms underlying cellular and organismal response to stress and stress-related disease; (2) Stress- and disease-related alterations in glucocorticoid receptor and heat shock proteins expression; (3) Stress- and disease-related modulation of glucocorticoid receptor and heat shock proteins function Partners/Interests researcher Biochemistry Genetics Physiology Our potential partners should share similar scientific interest and should be able to conduct complementary research. The goal of the new project will be to gain new knowledge on the complex mechanisms regulating biological activity of glucocortcioid receptor (GR) with the focus on the role of heat shock proteins (Hsps) in chaperoning the receptor and modulating its basic biological functions. The results of the research should help to assess how important are the levels of the receptor and its individual isoforms expressed in particular cellular context for tissue sensitivity to glucocorticoids and for diversity of tissue specific effects of these hormones. They should also help to establish correlation between GR functional parameters and tissue responsiveness to glucocorticoids. Finally, our studies should contribute to understanding the role of GR and Hsps in pathogenesis and clinical course of stress related somatic and psychic disorders associated with dysfunction of these proteins. The somatic Biochemistry disorders of special interest are asthma, metabolic syndrome X, polycystic ovary syndrome and diabetes, while the psychic ones are posttraumatic stress disorder and major depressive disorder. While the molecular structure and the mechanisms of GR functioning are now well established, the mechanisms modulating GR activity and expression, as well as those underlying diversity of tissue specific effects of glucocorticoid hormones remain largely unknown. Among other processes, these complex mechanisms include action of Hsps and posttranslational modifications of the receptor. They operate at almost every step of glucocorticoids action, from binding to the receptor to stimulation/inhibition of target genes transcription, exerting major influence on tissue sensitivity to these hormones. In order to better understand mechanisms responsible for modulation of GR expression and activity, in our studies we will exploit different corticosteroid related pathophysiological and stressful conditions to follow alterations in GR expression and function. A part of our research will be focused on human GR from peripheral blood mononuclear cells as readily available human cells that reflect situation in immune and neural tissue. Using quantitative Western blot technique and real time PCR, as well as standard hormone binding and tissue sensitivity assays we will examine the levels of GR protein and mRNA, its hormone binding capacity and affinity, as well as the expression of the two receptor isoforms in stress related diseases, including somatic and psychic disorders mentioned above. For example, knowing that posttraumatic stress disorder and major depressive disorder are associated with the opposite changes of hypothalamo pituitary adrenocortical axes sensitivity to glucocorticoids, these diseases will be exploited as a suitable model for studying modulation of GR function. At the same time, these studies will contribute to better understanding of the role of GR in pathogenesis of the studied diseases. Human GR will also be investigated in patients suffering from mild and severe forms of asthma, a disease almost inevitably connected to corticosteroid treatment. Asthma is characterized by inflammation and generation of reactive oxygen and nitrogen species in respiratory tract, and in our research will be employed for examining posttranslational modifications of the receptor, such as oxidation of cysteine and nitration of tyrosine residues. A part of our research concerning the effects of stressors such as hyperthermia and heavy metals on GR structural and functional properties will be performed on rat liver and kidney GR. Special attention will be paid on the role of heat shock proteins (Hsp90 and Hsp70) in chaperoning the receptor and modulating its function, as well as on their modifications potentially connected to their general role in cellular response to different stressors and in pathogenesis of somatic diseases. For analysing functional interactions of these proteins with GR we will apply coimmunoprecipitation and quantitative Western blot to follow stress related changes in Hsps levels in the cell and within GR multiprotein heterocomplexes. Institution/University Name of Institution/University Institute for Biological Research "Sinisa Stankovic" Number of Employees 230 Number of Researchers 192 Country Serbia and Montenegro Postal Adress Despot Stefan Boulevard 142 11000 Belgrade Biochemistry Research Team Research Team Name Institute Vinca, Laboratory for Molecular Genetics Individual Researcher No Research Team Leader Name PhD Esma Isenovic Research Team Members Team Member 0 Bs.Sci Jelena Velebit [[email protected]] Team Member 1 PhD Ljiljana Markovic [[email protected]] Team Member 2 Bs.Sci Emina Sudar [[email protected]] Team Member 3 Mr.Sci Snezana Tepavcevic [[email protected]] Team Member 4 Mr.Sci Mojca Vulovic [[email protected]] Team Member 5 PhD Zorica Zakula [[email protected]] Team Member 6 PhD Goran Koricanac [[email protected]] Team Member 7 PhD Esma Isenovic [[email protected]] Team Member 8 MD,PhD Biljana Putnikovic [[email protected]] Team Member 9 PhD Milan Orlic [[email protected]] Team Member 10 MD, MSci Zoran Gluvic [[email protected]] Research Team Projects Project Name Molecular mechanisms of transduction of hormonal signals: Biological markers of Modifications and integrations of signaling pathways in physiological and pathophysiological conditions. Project Leader PhD, Res Associate Prof Esma Isenovic [[email protected]] Project Funding Agency Ministry of Sciences of Republik Serbia Project Budget 10000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary Diabetes mellitus is a powerful risk factor for the development of cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in persons with diabetes. Insulin (INS) and Insulin like growth factor -1 (IGF-1) induces vasorelaxation in part by enhancing nitric oxide (NO) production and Na+, K+-ATPase (Na+pump) activation in vascular endothelial (EC) smooth muscle cells (VSMC). Estradiol (E2) like IGF-1 and INS normally exerts vasodilatory and protective effects by increasing vascular NO and VSMC Na+pump activity, among other mechanisms. Our preliminary studies indicate that IGF-1 and E2 are one of the regulators of NOS and Na+ pump in vitro, and their effects are mediated by cascade of 3 eznymes: phosphatidylinositol 3 kinase (PI3K)-cytosolic phospholipase 2 (cPLA2)-protein kinase B (Akt). As IGF-1 and E2 exert similar actions on NO and Na+pump activity in vascular tissue, we anticipate that they act synergistically to increase NOS/ Na+pump. We hypothesized that, when PI3K-cPLA2-Akt signaling cascade is interrupted ( i.e. INS resistance or molecular knockout pathway) , sinergisam of the IGF-1 and E2 will be abolished. The reninangiotensin system (RAS) is important in the pathogenesis of hypertension and associated CVD. Hypertensive patients are more likely than normotensives to develop type 2 diabetes and this propensity may reflect resistance to INS and a reduction in the ability of INS to promote relaxation and glucose (GLU) transport in vasculature and skeletal muscle tissue, respectively. Resistance to INS exists in vascular as well as skeletal muscle and adipose tissue (major sites of INS-mediated GLU disposal). Preliminary data from our laboratory, as well as others, suggest that angiotensin 2 (Ang II), acting through its AT1 receptor (AT1R), inhibits the actions of INS in vasculature, skeletal muscle and adipocytes via increases in RhoA activity. We seek to test the hypothesis that Ang II stimulation of Rho A compromises vascular INS/Akt signaling and consequent NOS/Na+,K+-ATPase activation and GLU disposal in INS resistant models of hypertension. The proposed studies will provide unique insights into alternative pathways linking IGF-1, INS and E2 signal transduction with cardiovascular diseases, thereby providing sites for gene and/or drug therapy. Project Website Biochemistry Project Name EU coperation Grant COST B17: “Obesity and Diabetes mellitus in the Elderly” Project Leader ResAssoProfe Esma Isenovic [[email protected]] Project Funding Agency COST EU Project Budget 100000 € Project Start Date 1999-12-16 Project End Date 2005-12-15 Project Partners Austria Professor K.h. TRAGL Austria Professor Josef PATSCH Belgium Professor Louis HUE Cyprus Dr. Joseph KASIOS Czech Republic Professor Jaroslav VESELY Czech Republic Dr. Bela BENDLOVA Denmark Dr. Christine REYNET Denmark Dr. Aase HANDBERG France Professor Emmanuel VAN OBBERGHEN Germany Professor Juergen ECKEL Greece Dr. Effie TSILIBARI Greece Professor George DIMITRIADIS Hungary Dr. György GYERMENDY Ireland Dr. John NOLAN Israel Professor Shlomo SASSON Israel Professor Nava BASHAN Italy Dr. Francesco GIORGINO Lithuania Dr. Vaidotas URBANAVICIUS Lithuania Dr. Valentinas MATULEVICIUS Netherlands Dr. J.a. MAASSEN Norway Professor Arild Chr. RUSTAN Norway Dr. Jorgen JENSEN Poland Professor Aldona DEMBINSKA-KIEC Romania Professor Dan CHETA Romania Dr. Maya SIMIONESCU Serbia and Montenegro Dr. Esma ISENOVIC Slovak Republic Title Elena SEBOKOVA Slovak Republic Dr. Iwar KLIMES Slovenia Professor Robert ZOREC Slovenia Professor Marjan KORDAS Spain Dr. Isabel VARELA-NIETO Spain Professor Margarita LORENZO Spain Dr. Antonio ZORZANO Sweden Professor Juleen ZIERATH Sweden Professor Jan ERIKSSON Switzerland Dr. Markus NIESSEN Switzerland Professor Jean-Louis CARPENTIER United Kingdom Professor Kenneth SIDDLE Project Summary Diabetes mellitus of aged people is a considerable health burden of western societies. At present no widely established screening method is available to detect the persons who are predisposed to this condition. Due to our incomplete knowledge of the molecular mechanisms leading to NIDDM we have few means to influence the onset and development of this diverse disease. The ongoing research of candidate genes as well as various differential screening methods are coordinated with this Action. Various steps of insulin action are studied starting from the insulin receptor and following insulin action until it reaches the cell nucleus. There is special emphasis on the investigation of pathological changes of the molecular mechanism of insulin action in insulin resistance, obesity and NIDDM of the aged people. This research activity leads to the development of new drug-candidates for the curingeasing of the consequences of the disease. Project Website http://www.webio.hu/workshop/cost Project Name European Commission Framework Programme: Equal Project (EC4): Multi-National External Quality Assay (EQA) Programmes in Clinical Molecular Diagnostics based on Performance and Interpretation of PCR assay including dissemination and training, supported by the European Community within the FP6 Project Leader ResAssProf particicapnt: Esma Isenovic [[email protected]] Project Funding Agency EU Project Budget 739000 € Project Start Date 2004-01-01 Project End Date 0000-00-00 Project Partners Prof. M. Pazzagli Department of Clinical Physiopathology University of Florence, Italy www.dfc.unifi.it Dr. R. Jansen European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) Geldrop, The Netherlands www.ec-4.org Prof. M. Neumaier Faculty for Clinical Medicine, University Hospital Mannheim of the University of Heidelberg, Germany www.ma.uniheidelberg.de/inst/ikc Prof. J.C. Libeer Scientific Institute of Public Biochemistry Health, Clinical Biology Department Brussels, Belgium www.eqalm.org A. Martens, MD ZiekenhuisGroep Twente Almelo, The Netherlands www.zgt.nl Dr. S. Ramsden UKNEQAS for Molecular Genetics Manchester, UK www.ukneqas-molgen.org.uk Dr. D. Taruscio Istituto Superiore di Sanità Rome, Italy www.iss.it Prof. V. Palicka Institute for Clinical Biochemistry and Diagnostics Medical Faculty and Teaching Hospital Hradec Kralove, Czech Republic www.fnhk.cz Project Summary Molecular biology based technologies and Genomic studies have opened new perspectives in diagnosis, prognosis and treatment of Clinical Medicine. Molecular Diagnostics are now available for the Clinical Chemistry and Medical Genetic laboratories but the level of standardisation of these tests in terms of instrumentation, reagents and procedures is, at the moment, lower than the usual Laboratory Medicine tests. External quality assurance (EQA) programmes for molecular diagnostics have been developed in order to safeguard quality of these assays, but up till now EQA programs addressed to specific DNA/RNA targets remain limited to a few tests. The Partners of the Project, Coordinators of EQA programmes of molecular diagnostics already implemented at national or international level, propose a panel of EQA programmes on Performance and Interpretation of PCR based assay methods. These methodological EQA programmes will be available to laboratories performing Molecular Diagnostics on a voluntary basis for monitoring performances of technical procedures common to most of these methods. Specifically developed questionnaires and procedures of data analysis will be implemented for monitoring efficacy and appreciation of these EQA programmes.Diffusion of these EQA programmes to other countries will be supported through international organisms of the area of Laboratory Medicine, such as EC4. Finally specific training courses will be organised by the partners for the participants of this survey in order to improve both technical and interpretation skills required for the correct use of these molecular diagnostic tests. It is expected that integration between EQA programmes addressed to methodological aspects and to specific analytes, with appropriate international training activities will improve the quality of molecular diagnostics. Project Website http://www.ec-4.org/ Project Name “Insulin-like Growth Factor-1 (IGF-1) Regulation of Nitric Oxide Synthase (NOS) and Sodium Pump in Type 1 Diabetes “ Project Leader ResAssoProf Esma Isenovic [[email protected]] Project Funding Agency MNT and EDGE Project Budget 1750 € Project Start Date 2006-01-01 Project End Date 3007-12-31 Project Partners CNRS UMR, Univ P& M Curie, Paris, France ( Dr. P. Marche) Project Summary Insulin-like growth factor-1 (IGF-1), acts in an autocrine/paracrine fashion on vascular smooth muscle cells (VSMC) and cardiomyocytes. IGF-1 is known to diminish vascular tone by modulating cation and nitric oxide (NO) metabolism IGF-1 increases vascular inducible NO synthase (iNOS) and Na+, K+-ATPase (sodium pump) expression and activity via a phoshatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling in VSMC. Cytosolic phospholipase 2 (cPLA2) is known to regulate Na+ pump activity. Vascular cPLA2 activity is increased by IGF-1 treatment. We hypothesize that in type 1 diabetes the decreased ability of IGF-1 to stimulate iNOS and Na+ pump activity is due to altered PI3K-cPLA2-Akt signaling cascade, which modulates iNOS and sodium pump activity/expression. Project Website http://www.egide.asso.fr; http://www.mntr.sr. Project Name “Response to insulin on cellular level” Project Leader ResAssProf Esma Isenovic [[email protected]] Project Funding Agency Ministry of Sciences Serbia and Slovenia Project Budget 2500 € Project Start Date 2006-01-01 Project End Date 2007-12-31 Project Partners University of Ljubljana, Slovenia (Prof. R. Zorec) Biochemistry Project Summary Objective: INS resistance (decreased tissue INS action) is characterized by one or more postbinding defects that mediate INS stimulation of GLUT. Reduced INS sensitivity is a characteristic feature of various pathological conditions such as type 2 diabetes and hypertension. Hypertensive patients are more likely than normotensives to develop type 2 diabetes and this propensity may reflect resistance to INS and a reduction in the ability of INS to promote relaxation and GLUT in adipose tissue and skeletal muscle cells, respectively. Recent studies suggest that these action of INS is mediated through the activation of phosphatidylinositol-3-kinase (PI3K) and the downstream, protein kinase B (Akt) signaling cascade. This signaling pathway increases GLUT in adipocytes and skeletal muscle tissues. Thus, functional alterations in these INS signaling pathways are likely to play an important role in these pathologies. In this regard, there is emerging evidence that angiotensin II (Ang II) interferes with this signaling, resulting in a state of resistance to INS mediated GLUT; however, the role of intermediary signaling molecules are unclear. Hypothesis: Although we intend to further explore the actions of INS in cultured skeletal muscle cells, the major thrust of our proposal seeks to test our primary hypothesis: INS regulates in skeletal muscle cells GLU metabolism, in part, by increasing the mobilization of the INS sensitive- GLUT-4 to the PM by exocytosis. Specifically, we hypothesize that Ang II attenuates the ability of INS to increase GLU permeability of skeletal muscle cells by interfering with signaling through the PI3K/Akt in skeletal muscle cells. Description of the project: Since, exocytosis of vesicles is associated with an increase in plasma membrane surface area that can be monitored by electrophysiological measurements of membrane capacitance; we will employ confocal microscopy to observe the changes in PM area after stimulation with INS and/or Ang II. The proposed studies employing single cultured skeletal muscle cells will be used to answer the following key questions. 1) Do INS and Ang II induce changes in PM area and mobilization of GLUT4 to the PM? 2) Whether PI3K/Akt signaling pathway is involved in mediating interactions between Ang II and INS in regulation of GLUT and GLUT 4 mobilizations to the PM? Project Website www.mnt.sr.gov.yu Contact Person Name PhD Esma Isenovic Email [email protected] Function Principal Investigator, Associate Res Professor Phone +381647029163 Fax +381112159978 Website www.vin.bg.ac.yu Research Team Objectives Main Fields Biochemistry Internal Medicine Public health services Investigations focused on characterization of the effects of different hormones such as insulin, IGF-1, Ang II and estradiol in order to address critical questions regarding the impact of disease (i.e., diabetes, hypertension). Studies were carried out in primary cultures of vascular smooth muscle cells, rat aortic endothelial cells and adult cardiomyocytes. In vivo studies were carried out in different rat models (Zucker obese, mREN etc) Partners/Interests researcher Biology Internal Medicine Public health services Well established scientists with interest in the field of metabolic syndrome. Insulin resistance (IR) is usually characterized by a) higher levels of insulin (INS) while fasting and post-glucose (GLU) loading, and b) decreased tissue responsiveness to INS-driven clearance of GLU from the bloodstream. INS regulates blood GLU levels primarily by stimulating uptake of GLU by muscle and fat cells and curbing hepatic GLU output. GLU is transported via a family of GLU transporter proteins (GLUTs), with GLUT4 being the major INS-responsive isoform in muscle and fat. Intracellular GLUT4 is translocated to the cell surface in response to INS by a mechanism requiring activation of phosphatidyl-inositol (PI)3-kinase (P13K) and protein kinase B (Akt). IR seems to be a common feature and a possible contributing factor of several frequent health problems, including type 2 diabetes mellitus (DMT2), sleep-related breathing disorder (SRBD) and obesity. IR induced by a high-fat (HF) diet and associated obesity are major risk factors for DM and cardiovascular diseases. Epidemiologic studies have delineated strong links between obesity, dyslipidemia, IR or diabetes. But the question remains: The significance of adipose tissue for INS sensitivity became a major focus Biochemistry following the finding that this tissue is an active endocrine organ, secreting several factors (e.g., leptin and adiponectin) that can affect whole-body INS sensitivity. Adipocytes increase adiponectin synthesis in vitro in response to INS, which has a lesser effect in adipocytes from obese animals, although in vivo INS appears to decrease adiponectin levels. Infusion of INS and GLU to maintain euglycemia in humans leads to increased circulating leptin levels after 3 h. In rats with streptozotocin (STZ)-induced diabetes, leptin levels fall but can be restored by INS in a dose-dependent fashion, with prevention of the hyperphagia characteristic of uncontrolled diabetes. In cultured adipocytes, INS increases leptin production, which can be blocked with 2-deoxyglucose in a dose-dependent fashion, suggesting that GLU uptake is required for an effect on leptin.. Understanding the complex interaction between IR, and obesity may lead to more effective, better tolerated treatments for DMT2 and IR The mechanism by which INS and adipokines such as leptin and adionectin might be associated remains poorly understood, and will be be further addressed in my future work . Institution/University Name of Institution/University Institute Vinca Number of Employees 850 Number of Researchers 450 Country Serbia and Montenegro Postal Adress Mike Alasa 15 11000 Beograd Biochemistry Research Team Research Team Name Laboratory for basic research in Urological Oncology Individual Researcher No Research Team Leader Name Prof. Dr. Tatjana Simic Research Team Members Team Member 0 Dr. Dejan Dragicevic [[email protected]] Team Member 1 Dr. Marija Opacic [[email protected]] Team Member 2 Dr. Marija Pljesa-Ercegovac [[email protected]] Team Member 3 Dr. Ana Savic-Radojevic [[email protected]] Team Member 4 Prof. Dr. Jasmina Mimic-Oka [[email protected]] Team Member 5 Prof.Dr. Tatjana Simic [[email protected]] Research Team Projects Project Name Role of glutathione S-transferases in urinary tract carcinomas Project Leader Prof.Dr. Tatjana Simic [[email protected];[email protected]] Project Funding Agency Ministry of Science and technology of Serbia Project Budget 36000 € Project Start Date 2006-01-01 Project End Date 2007-12-31 Project Partners Serbia, University of Belgrade, Institute of Biochemistry Serbia, University Clinical Centre, Institute of Urology and nephrology Project Summary Urinary tract organs have an important role in excretion of endogenous and exogenous metabolites. Therefore, kidney tissue and epithelium of renal pelvis, ureters and urinary bladder are exposed to various xenobiotics, including carcinogens. Exposure to potential carcinogens is among etiological factors for renal cell carcinoma and transitional cell carcinoma of urinary bladder. Renal cell carcinoma is very resistant, while transitional cell carcinoma of urinary bladder exibit high recurrence and multifocality. Glutathione S-transferases (GSTs) may play an important role in occurrence, progression and resistance of these tumors. Cytosolic GSTs are a superfamily of enzymes (classes alpha, mu, pi and theta), which protect normal cells by catalyzing conjugation reactions between electrophylic compounds and glutathione. In tumor cells, GSTs are responsible for resistance to antitumor drugs. Certain GSTs also have regulatory role in regulation of mitogen-activated protein kinases (MAPK), involved in induction of apoptosis. To discern the role of GSTs in urinary tract carcinomas, whithin this project we aimed to (1) identfy unknown and known GST isoenzymes and clarify their role in the occurrence and resistance of these tumors (2) establish whether relationship between GST expression at protein level and tumor progression exists and if any of GST isoenzymes might be used as tumor marker (3) determine whether interactions between GST and MAPK exist and clarify regulatory role of GST isoenzymes in regulation of apoptosis. Contact Person Name Prof. Dr. Tatjana Simic Email [email protected] Function Associated Professor, Institute of Biochemistry Phone +381 11 2645750 Fax +381 11 2645750 Website http://www.med.bg.ac.yu Research Team Objectives Main Fields Biochemistry The laboratory for Basic research in Urological Oncology belongs to the Institute of Biochemistry, Medical Faculty, Belgrade. Our scientific group is composed by one full Professor (Jasmina MimicOka), one associated professor (Tatjana Simic), one post Doctorate Researcher (Ana Savic Radojevic) and two PhD Candidates (Marija Pljesa-Ercegovac and Marija Opacic). Clinical urolgist Dr Dejan Biochemistry Dragicevic, PhD, engaged as teaching assistant at our Faculty, is also member of the group. Our studies have been funded by national Minsitry of Science and technology. Members of the team have an expertise on the fields of enzymology, oxidative stress and malignant phenotype of urinary tract carcinomas. The major aim of the team is to elucidate the role of glutathione S-transferases (GST) in urinary tract tumors. GSTs are xenobiotic-metabolyzing enzymes which play a role in response to exposure to carcinogenic chemicals as well as in chemoresistance and apoptosis of tumor cells. Therefore, we aim to perform systematic functional investigation of different GST classes in transitional cell carcinoma of urinary bladder and upper urothelial tumors, by using an array of substrates of differential specificity and Western blot. Corresponding non-tumor tissue will also be studied. Glutathione (GSH) level and the activities of key enzymes involved in its synthesis, replenishment and degradation, together with the activity of antioxidant enzymes will be measured. The scientific excellence of the group is proven by the bibliographic entries. Major equipment •Equipment for purification and characterization of proteins (enzymes) including affinity chromatography, chromatofocusing, isoelectric chromatofocusing, electrophoresis, Western blot, immunoassays •Equipment for spectrophotometric measurement of the activities of glutathione Stransferases, antioxidant enzymes (GSTs, gamma-glutamyl transpeptidase, gamma-glutamyl cysteine synthetase, glutathione reductase, glutathione peroxidase and superoxide dismutase) and quantification of free radical activity (isoprostane analysis, carbonyl groups, malondialdehyde etc.). Partners/Interests researcher Biochemistry Toxicology We search for partners which have an expertise on the fields of MAP kinase pathways, with specific emphasis on JNK pathway and its role in apoptosis. Partners that have excellence on the study of protein:protein interactions by means of confocal microscopy or other methods would be also welcome. We also search partners engaged in investigations of malignant phenotype of transitional cell carcinoma, especially those that study proteome and metabolome of transitional cell carcinoma and bladder tumor cell lines. It would be of interest to find partners involved in the research of agents that modulate GST activity/expression in in vitro conditions. Bladder cancer has been cited to result from the neoplastic lesion with environmental and/or occupational factors identified as causatives. Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Most of the bladder cancer patients die from the invasive, metastatic TCC that shows resistance to chemotherapy. Glutathione S-transferase (GST) superfamily members have been shown to be involved in chemotherapy resistance of many human tumors. Our studies on the expression of GST in uroepithelium and transitional cell carcinoma of urinary bladder have shown significant upregulation of GSTP1-1 in tumor cells. Recently, a new antiapoptotic role for GSTP1-1 has been described. Namely, GSTP1-1 potently and selectively inhibits activation of c-jun protein by its upstream kinase, c-jun NH2-terminal kinase (JNK). The JNK belongs to the family of stress kinases and has been shown to be required for the induction of apoptosis by DNA-damaging agents. Recently, an inhibition of JNK activity by GSTP1-1, which was reversed by polymerization induced by oxidative stress, has been reported in mouse fibroblast cell lines. This newly identified regulatory activity of GSTP1-1 is strongly inhibited by a group of agents (7-nitro-2, 1, 3-benzoxadiazole derivatives). The cytotoxic mechanism of these inhibitors has been carefully investigated in leukemic CCRF-CEM and K562 cell lines. Western blot and immunoprecipitation analyzes have shown that 6-(7-nitro-2, 1, 3benzoxadiazol-4-ylthio) hexanol promotes in both cell lines the dissociation of the GSTP1-1 from a complex with JNK. This process triggers a reactive oxygen species (ROS)-independent activation of the JNK-mediated pathway that results in a typical process of apoptosis. In the present study we aim to examine whether GSTP1-1 have antiapoptotic role in the transitional cell carcinoma of urinary bladder. Besides we will also examine whether such role is medited by GSTP1-1:c-jun NH2-terminal kinase interaction and how it depends on cellular redox balance. Therefore it is of particular interest to determine whether such interaction exists in tumor specimens as well as in transitional cell carcinoma cell lines such as 5637, BFTC905, HT1197, J82, SCaBER, T24, TSGH-8301, and TCCSUP T24. In case we prove antiapoptotic role of GSTP1-1 in bladder tumor cell lines, cytotoxic activities of new 7-nitro-2, 1, 3-benzoxadiazole derivatives will be tested as promising anticancer agents. Institution/University Name of Institution/University University of Belgrade, Medical Faculty Number of Employees 861 Number of Researchers 861 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Biochemistry Research Team Research Team Name Molecular biology of mental disorders Individual Researcher No Research Team Leader Name BSc, PhD Dorotea Mück-Seler Research Team Members Team Member 0 PhD student Martina Dezeljin [[email protected]] Team Member 1 PhD student Maja Mustapic [[email protected]] Team Member 2 PhD Nela Pivac [[email protected]] Contact Person Name BSc, PhD Dorotea Mück-Seler Email [email protected] Function senior scientist Phone 385-1-4571 207 Fax 385-1-4561 010 Website www.irb.hr Research Team Objectives Main Fields Biochemistry Genetics Psychiatry The investigation of the peripheral biochemical markers in the etiology of schizophrenia, depression and Alzheimer's disease. Genes and mental disorders. Pharmacogenomics and proteomics Partners/Interests researcher Psychiatry Pharmacology Genetics Experienced psychiatrist or neurologist Biochemical and genetical markers, in the prediction of the treatment response in depression (unipolar, bipolar), schizophrenia Institution/University Name of Institution/University R.Boskovic Institute Number of Employees 700 Number of Researchers 400 Country Croatia Postal Adress Bijenicka 54 10000 Zagreb Biochemistry Research Team Research Team Name Molecular Medicine Unit, Institute of Biochemistry, Faculty of Medicine, University of Belgrade Individual Researcher No Research Team Leader Name Dr. Ivanka Markovic Research Team Members Team Member 0 Dr. Tatjana Radnic [[email protected]] Team Member 1 Dr. Sonja Misirlic Dencic [[email protected]] Team Member 2 Dr. Olivera Vuckovic [[email protected]] Team Member 3 Dr. Aleksandra Isakovic [[email protected]] Contact Person Name Dr. Ivanka Markovic Email [email protected] Function Associate Professor Phone +381-11-2683-841 Fax +381-11-2682-953 Website www.med.bg.ac.yu Research Team Objectives Main Fields Biochemistry Clinical chemistry Neurology The main fileds of interest are the role of nucleosides and their analogues in idifferent cellular processes; furthermore, we are interested in the biochemical and molecular mechanism of neurodegenerative disorders. Existing facilities at Institute of Biochemistry offer an opportunity to investigate the biochemical and structural bases of molecular and cellular processes in a variety of mammalian cells, using live-cell investigation (cell culture, protein expression, cell cycle, intracellular signalling, etc.), gene expression, use of fluorochromes for identification and quantification of different markers involved in cellular processes, and a number of other techniques useful in studying and understanding cellular and molecular mechanisms that regulate cells’ responses to different stimuli. Partners/Interests researcher industrial partner Biology Clinical chemistry Neurology The partner should have similar research interests (mainly but not restricted to biochemical and molecular aspects of neurodegeneration) together with research methodology and know-how that is compatible to ones we use. We would also appreciate if a potential partner would have experience and expertise in molecular biology and genetic manipulations (creation of constructs, work on knockout animal models etc) or if our potential partner would be interested in testing of biological activity and metabolic fate of different synthetic compounds. Our research interests in the following period are mainly focused on different aspects of functioning of the cells of the CNS (astrocytes, choroid plexus epithelium, endothelial cells and neurons) in physiological and pathological conditions, using in vivo and in vitro models, as well as how the interactions between the cells change upon action of different noxious influences (i.e. molecular and biochemical aspects of degeneration and cell death). The main focus of future research will be work on primary cell cultures (rat astrocyte and neuronal culture, choroid plexus epithelium, brain andothelial cells) and biochemical and molecular investigation of the cells originating from the clinical samples (function of monocyte-derived macrophages and dermal fibroblast in patients from neurodegenerative disorders). The research activities would employ a wide range of approaches, including molecular and cell biology, biochemistry, multi-color FACS analysis, cell imaging using confocal microscopy etc. Furthermore, the existing research methodology and know-how at our Unit enables us to investigate the transfer of compounds across the barriers of the brain (BBB and bloodCSF barrier) using both in vivo and in vitro models (mechanism and kinetics of transport). Biochemistry Institution/University Name of Institution/University University of Belgrade, Faculty of Medicine Number of Employees 1400 Number of Researchers 850 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Biochemistry Research Team Research Team Name Research team for biophysical chemistry and enzymology Individual Researcher No Research Team Leader Name Dr Vesna Vasic Research Team Members Team Member 0 Dr Danijela Krstic [[email protected]] Team Member 1 Bsc Mirjana Colovic [[email protected]] Team Member 2 Msc Katarina Krinulovic [[email protected]] Team Member 3 Bsc Ana Vujacic [[email protected]] Team Member 4 Msc Jasmina Savic [[email protected]] Team Member 5 Msc Tatjana Momic [[email protected]] Contact Person Name Dr Vesna Vasic Email [email protected] Function senior researcher Phone +381 11 2453 967 Fax +381 11 444 7207 Website vin.bg.ac.yu Research Team Objectives Main Fields Biochemistry Toxicology Information Technology, Statistics, Documentation The main field of the interest is the study of the enzyme inhibitors and inhibitory processes and agonist / antagonist receptor interactions in the development of medicinal cardiotonic, antiviremic and anti-cancer agents and an understanding of their action. The special attention is given to the structure and molecular aspects, enzyme kinetics, inactivation and reactivation mechanism, structure – activity relationships (QSAR, graphic tecniques), drug development studies, drug release and control mechanisms in metabolic processes. Research covers several topics: 1. The toxicology study of biologically active compounds with the promissing pharmacological qualities (synthetic drugs, extracts from medical plants, antitumor, antibacterial and antiviral complexes) is oriented to the in vitro investigation between the selected compounds and aminoacids, peptides and enzymes as the basis for better understanding of their toxic or therapeutic properties. 2. The modulation of the activity of therapeutically and toxicologically important enzymes (ATPases, peroxidases, cholynesterases) induced by selected compounds has been be studied, as well the indicators of oxidative stress (lipid peroxidation, malondialdehyde). 3. The the methodological standardization of procedures for protein isolation from human materials (erythrocytes, cell culture), enzyme immobilization in non-conventional media and development of methods for in vitro and in vivo evaluation of enzyme activity. Various techniques are available (stopped flow, UV VIS, UPLC, PCR, GSMS, MALDI-TOF MS, SEM) to elucidate the structure-activity relationships, particularly the effects of chemically well defined compounds on selected parameters of biochemical reactions. Partners/Interests researcher industrial partner Biochemistry Toxicology Pharmacy Institution/University Name of Institution/University Vinca Institute of Nuclear Sciences Number of Employees 800 Number of Researchers 400 Country Serbia and Montenegro Postal Adress Vinca, Mike Alasa 6 11001 Belgrade Biochemistry Research Team Research Team Name Individual Researcher No Research Team Leader Name dr. Urška Čegovnik, univ. dipl. kem Contact Person Name dr. Urška Čegovnik, univ. dipl. kem Email [email protected] Function Phone +386 4 2569 490 Fax +386 4 25 69 117 Website http://www.klinika-golnik.si/ Research Team Objectives Main Fields Biochemistry Molecular Biology Partners/Interests Biochemistry Molecular Biology Aspirin Hypersensitivity: Sensitivity to aspirin (acetylsalicylic acid) consists of steroid-dependent asthma and nasal polyposis (rhinosinusitis). Aspirin hypersensitivity syndrome is thought to be caused by a decrease in the levels of the anti-inflammatory E2 prostaglandin (PG), along with an increase in the levels of pro-inflammatory leukotrienes (LTs). Our aim is to determine the gene expression intensity of some key proteins implicated in the pathogenesis of aspirin induced asthma and rhinosinusitis. Intensity of gene expression is measured by Real-time PCR based on TaqMan technology. Institution/University Name of Institution/University University Clinic for Respiratory and Allergic Diseases Golnik Number of Employees Number of Researchers Country Slovenia Postal Adress Golnik 36 4204 Golnik Biology Research Team Research Team Name Individual Researcher No Research Team Leader Name Dr Ljiljana Vicovac Research Team Members Team Member 0 MSci Zanka Bojic-Trbojevic [[email protected]] Team Member 1 MSci Milica Bozic [[email protected]] Team Member 2 BS Milica Jovanovic [[email protected]] Team Member 3 MD, PhD Ljiljana Radojcic [[email protected]] Team Member 4 MD, PhD Nebojsa Radunovic [[email protected]] Team Member 5 MD, PhD Milos Petronijevic [[email protected]] Research Team Projects Project Name Role of local factors in the implantation of the human embryo Project Leader dr Ljiljana Vicovac [[email protected]] Project Funding Agency Ministry of Science and Technology, Serbia Project Budget 172000 € Project Start Date 2002-01-01 Project End Date 2005-12-31 Project Partners Belgrade University, Medical Faculty; Medical Military Academy; Begrade Project Summary Implantation of the human embryo critically depends on a strictly controled sequence of cellular events that include adhesiveness, proliferation and invasiveness of cell populations. Deviations of the norm are related to serious pathological conditions and may compromise pregnacy. It has been shown that a group of extravillous cytotrophoblast cells that are in physical contact with endometrial stroma express a specific phenotype and gain full invasiveness.Factors that regulate differentiation of trophoblast are not suffiiently understood. The project aimed to study expression of differentiation markers in situ in normal and transformed trophoblast and possible effects of maternal factors in vitro, using the accepted in vitro models. Project Website Project Name Cellular interactions and molecular mechanisms in differentiation of cells at the feto-maternal interface Project Leader dr Ljiljana Vicovac [[email protected]] Project Funding Agency Ministry of Science and Environment protectio Project Budget 250000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Medical faculty, University of Belgrade; Medical Military Academy, Belgrade; Project Summary Many aspects of the process of embryo implantation are still insufficiently understood. Physiological invasion of uterine tissues by human placental trophoblast is crucial for embryonic development but molecular processes involved remain largely obscure. Both shallow invasion, which is linked to the pathogenesis of the maternal hypertensive disorder pre-eclampsia and to fetal growth retardation, as well as the excessive proliferation and invasion cause serious and life threatening conditions. Recently, much progress has been made regarding the trophoblast intrinsic regulatory factors and multitude of cytokines present localy at the time of implantation. There is, however, still need for further ellucidation of the role of some uterine and other locally present factors on invasive trophoblast differentiation. It is proposed here to utilize different trophoblast cell models to study the effects of the selected cytokines, chemokines, hormones or autoantibodies, on trophoblast differentiation, apoptosis, cell migration and invasivenes. Regulatory factors and signalling pathways Biology will be studied in vitro at the protein and mRNA level, based on cellular markers, and functional tests. The project will provide insights into the role of some decidual products on the differentiation of invasive trophoblast and their relevance for normal implantation and pregnancy. Project Website Contact Person Name Dr Ljiljana Vicovac Email [email protected] Function Principal Investigator Phone 381-11-619-252 Fax 38111618724 Website www.inep.co.yu Research Team Objectives Main Fields Biology Obstetrics and Gynaecology Biochemistry Main fields of interest of the research team include: cell biology of embryo implantation, trophoblast cell invasiveness, placental function, pregnancy related aspects of endometrial structure/function Partners/Interests researcher Biology Obstetrics and Gynaecology Expertise in the application of molecular tools to the field of biology of embryo implantation. Partners interested in the same field are sought for collaborative basic or applied research. Institution/University Name of Institution/University Institute for the Application of Nuclear Energy INEP, B U Number of Employees 82 Number of Researchers 29 Country Serbia and Montenegro Postal Adress Banatska 31b 11080 Zemun-Belgrade Biology Research Team Research Team Name glycobiology team Individual Researcher No Research Team Leader Name senior research fellow Miroslava Jankovic Research Team Members Team Member 0 MSc Bojana Tapuskovic [[email protected]] Team Member 1 MSc Maja Kosanovic [[email protected]] Team Member 2 MSc Snezana Golubovic [[email protected]] Team Member 3 PhD Ljiljana Hajdukovic [[email protected]] Team Member 4 PhD Miroslava Jankovic [[email protected]] Research Team Projects Project Name Glycans as molecular markers of cell function: expression, microheterogeneity and biosignalling properties Project Leader PhD Miroslava Jankovic [[email protected]] Project Funding Agency Ministry for Science Project Budget 240000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners No Project Summary In this project we will investigate expression, microheterogeneity and biosignalling properties of glycans as molecular markers of cell function. The special emphasis will be set on their role in molecular patterning in prostate, ovarium, breast, colon, and placental tissue. Glycomic profiling will comprise the common pattern of expression of N- and O-glycans, as well as the analysis of glycoforms of molecules with known marker potential. Parallely to glyco-phenotype, the lectin phenotype will be also analyzed, aiming at the insight in lectins as link between glyco-signals and cell responces. Methodological approach will be based on affinity techniques using lectins and carbohydrate-specific antibodies. The results obtained will be analyzed from aspect concerns the gain or loss of cell function, different growth and differentiation stages, environmental influences and immunological status, and all of this in the context of the existence of network of reactive components in the cell, on the cell and in extracellular matrix. It is expected that the results obtained led to better understanding of the regulatory and adaptive potential of glycosylation and to be a base for taking part in contemporary cources of glycobiological investigations. Project Website Project Name Glycobiological aspects of physiological and pathophysiological processes Project Leader PhD Miroslava Jankovic [[email protected]] Project Funding Agency Ministry of Science Project Budget 500000 € Project Start Date 2002-01-01 Project End Date 2005-12-31 Project Partners Serbia/University of Belgrade, Medical Faculty Project Summary The influence of endogenous and exogenous factors on synthetic and secretoty activities of human tissues (placenta, thyroid, liver etc.) based on the expression, structural characteristics and activity of particular types of lectins and physiologically active glycoproteins (oncofetal antigens, mucins, IGF system) was the subject of this research. Project Website Contact Person Name senior research fellow Miroslava Jankovic Email [email protected] Biology Function deputy director Phone +381 11 199 949 Fax +381 11 618 724 Website inep.co.yu Research Team Objectives Main Fields Biology Pathology Clinical chemistry Glycobiology: isolation and structural characterization of glycoproteins Lectinology: isolation, expression and activity of endogenous lectins (galectins and C-type lectins) Tumor marker research: development and production of solid phase binding assays (IRMA, RIA-CT, ELISA, ELBA) for quantitative determination of glycoprotein tumor markers; expression and structural characterization of glycoprotein tumor markers Partners/Interests researcher Biology Clinical chemistry Pathology Glycobiology: analysis of glycan structure (MS, glyco- and lectin-array and glycochip technology) Cell biology Cancer biology: tumor marker characterization 1. Glyco-profiling: investigation of the expression and microheterogeneity of glycans, aiming at differentially expressed components and establishing the correlation of their concentration to their structural properties in terms of introduction of the multi-biomarker pattern and the formulation of assays for their detection 2. Analysis of glycoforms of molecules with known marker potential (oncofetal antigens, hormones, immunoglobulines etc), using lectins and carbohydrate-specific antibodies. 3. Lectin-profiling: investigation of the expression and biosignalling properties of carbohydrate-binding proteins, aiming at the insight in lectins as link between glyco-signals and cell responces Institution/University Name of Institution/University Institute for the Application of Nuclear Energy, INEP Number of Employees 84 Number of Researchers 26 Country Serbia and Montenegro Postal Adress Banatska 31b 11080 Belgrade Biology Research Team Research Team Name Group for immunoparasitology Individual Researcher No Research Team Leader Name MD, PhD Ljiljana Sofronic-Milosavljevic Research Team Members Team Member 0 MD Marija Borovic [[email protected]] Team Member 1 M.sc Miomir Petrovic [[email protected]] Team Member 2 B.sc, M.sc Natasa Ilic [[email protected]] Team Member 3 B.sc., Ph.D Alisa Gruden-Movsesijan [[email protected]] Research Team Projects Project Name Components of molecular communication between host and parasite. Project Leader MD, PhD, Senior Research Fellow Ljiljana Sofronic-Milosavljevic [[email protected]] Project Funding Agency Ministry of Science and Technology, R.Serbia Project Budget 140716 € Project Start Date 2002-01-01 Project End Date 2005-12-31 Project Partners Project Summary Trichinellosis and toxoplasmosis rank very high among all food borne parasitic diseases in Serbia in last decades. Our research goals were: 1. to increase knowledge in basic science regarding host immune response to infection with macro- (Trichinella) and micro-parasites (Toxoplasma), 2. To achieve further insight in immunoregulatory and immunomodulatory mechanisms those exist during infection, 3. To enable the scientists in the country to continue to participate the coordinated research work on the international level regarding world wide and production of food safe meat. Project Website Project Name Cellular and molecular mechanisms of immune response and immune-regulation in parasitized host. Project Leader Md, PhD, Senior Research Fellow Ljiljana Sofronic-Milosavljevic [[email protected]] Project Funding Agency Min. of Sci. and Environmental Protec.,Serbia Project Budget 215000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary Humans co-evolved with parasites, but the complexity and medico-biological implications of this coevolution are not yet understood. Current research results are now reviling more parasitic components that are characteristic for all metazoans, including humans, implying that there are many direct interactions between the parasite and the physiological and immunological processes of the host. On that way parasite could influence the host immune response not only towards itself but to other exogenous (concomitant infectious, allergy) or even endogenous antigens (autoimmune diseases, tumors). Recent studies emphasized the importance of the cooperative interaction between innate and adaptive sources of factors in the generation of hypo-responsive state during some chronic parasite infectious. The scope of this project is to examine how parasites and their products: 1. influence the innate response of the host immune system, 2. create immunological environment that has impact on concurrent responses to autoimmune diseases, 3. could be further characterizedand applied in current diagnostic tools. Among expected results are: 1. better understanding on how different Trichinella spiralis antigens influence dendritic cell maturation, B1 lymphocyte activation and consecutive Th1/Th2 balance, 2. insight in mechanisms of modulation of autoimmune disease by T.spiralis infection, 3. further improvements on the programs of parasitic disease surveillance and secure food meat production. Biology Contact Person Name MD, PhD Ljiljana Sofronic-Milosavljevic Email [email protected] Function Senior research Fellow Phone +381 11 619 525 Fax +381 11 618 724 Website www.inep.co.yu Research Team Objectives Main Fields Biology Immunology and Immunohaematology Epidemiology Basic studies focus on host-parasite relationship, underlining immunoregulatory mechanisms and "protective role" of infections in autoimmune and allergic disease ("worm therapy" is gaining increasing interest in the scientific community). Applied research focuses on continuous improvement in the diagnosis of helminthic infections enabling their surveillance and control, as well as safe food (meat) production. Partners/Interests researcher Biology Immunology and Immunohaematology Epidemiology High competence in fields of immunoparasitology and molecular-biology 1.On the first place we are looking for partners in resaerch area that is described under title of currently running project "Cellular and molecular mechanisms of immune response and immuneregulation in parasitized host" (01.01.2006-31.12.2010); 2.The role of infectious agents (parasite, helminthes, T.spiralis) in allergy prevention; 3.Echinococcus spp., hydatidosis, immune response. Institution/University Name of Institution/University Institute for the Application of Nuclear Energy "INEP" Number of Employees 85 Number of Researchers 30 Country Serbia and Montenegro Postal Adress Banatska 31b 11080 Belgrade Biology Research Team Research Team Name Institute of Biology Bucharest Individual Researcher No Research Team Leader Name Dr. Madalin Enache Contact Person Name Dr. Madalin Enache Email [email protected] Function Scientific Director Phone +40 21 2239072 Fax +40 21 2219071 Website www.ibiol.ro Research Team Objectives Main Fields Biology Microbiology Other allied sciences Investigation of microorganisms from extreme environments (salt & acidophilic) environment; Bioremediation of polluted soils with heavy metals and hydrocarbons Partners/Interests researcher Microbiology Biology Other allied sciences research in the field of microbiology microbiology field Institution/University Name of Institution/University Institute of Biology Bucharest Number of Employees 129 Number of Researchers 102 Country Romania Postal Adress Splaiul Indepnedentei Str. 169 06003 Bucharest Biology Research Team Research Team Name Laboratory for Biological Research of the Cell (Team: Biomaterials application in Cell and Tissue Engineering) Individual Researcher No Research Team Leader Name Professor Stevo Najman Contact Person Name Professor Stevo Najman Email [email protected] Function Head of Department of Biology with Human Genetics Phone ++38118226712 Fax ++38118238770 Website medfak.ni.ac.yu Research Team Objectives Main Fields Biology Cytology Surgery Biomaterials are used in more then 10% of indicated surgical interventions what opens the door to the new technology and invention of the new biomaterials. Cell therapy, tissue engineering and gene therapy involved in this process too. Bone skeleton became prototype for tissue engineering. The goal of our research group is to find out optimal combination of induction signals, osteogenic cells and matrix which can imitate natural bone tissue. Some reports showed very optimistic results when bone substitution was used. Osteogenic cells are of mesenchimal origin. Mesenchimal cells (MC) are multipotential stem cells and could be found in different adult tissues: fat, muscle tissue, trabecular bone, bone marrow. Bone marrow is the most often taken as source for mesenchimal cells which can develop in to osteoblasts, myoblasts, adipocytes and chondrocytes. Mesenchimal cells are very small fraction (0.001%) of bone marrow cells. Both in vitro and in vivo studies showed that growth factor can induce expansion of mesenchimal cells and their differentiation to osteoblasts. Basic conditions for artificial matrix is biocompatibility and that it is support for cell attachment, proliferation and migration. Ideal matrix for orthopedic use should enable formation of bone tissue and its growth, revascularization, osteointegration with host bone and gradual replacement of artificial matrix with newly formed bone. Also it should have adequate mechanical properties for simple regenerative therapy. Designers and inventors of biomaterials get a heavy task to find out chemical properties, porosity, surficial and physical properties suitable for adequate interaction between cells and biomaterial. According to our previous results of in vivo and in vitro investigations of different biocomposite materials like HAp/PLAA composite the one of our aims is to solve the problems of preparation of adequate tissue matrix and its settlement with MC of bone marrow in intention to reach satisfying osteogenic potential. Multidiscipline approach to this problem will enable to carry out all key phases of the investigation: preparation of biomaterial, in vitro phase, in vivo tests on experimental animals and clinical use of selected matrixes. The preparation of biomaterials will consist of: creation of different combination of composites, modification of its surface which will modulate interaction between cells and connective matrix. Models got in cultures of mice bone marrow stroma cells settled to artificial matrix, will be used as base for same kind of investigations on human bone marrow stroma cells cultures. In vitro phase usage of biomaterials is capable for adequate morphology, biochemical, and molecular biology methods for estimation of the cell growth, adhesion ability and differentiation ability of the cells and enables us to predict the results of implantation. The suitable type of the cell culture medium and some supplements in medium including specific growth factors (BNPs) are responsible for induction and differentiation of osteogenic cells. The final estimation of osteogenic potential will be done after implantation. In vivo investigations will be carried out on experimental animals (mice, rats, rabbits). According to the aim of the experiment different kinds of implantation (intraperitoneal or subcutaneous) or filling up of the bone tissue defect will be used. The animals will be sacrificed periodically and samples of grafts and surrounding tissues analyzed in intention to make the estimation of the early regeneration period and of the period of expected complete implant integration with tissue. Different investigation methods will be used: post mortem examinations, pathohistology, specific staining for matrix tissue, SEM, TEM, haematological, biochemical, ELISA and RT-PCR tests. Partners/Interests researcher industrial partner Biology Biology Cytology Surgery Institution/University Name of Institution/University Medical Faculty University of Nish Number of Employees 435 Number of Researchers 340 Country Serbia and Montenegro Postal Adress Boul. Dr. Z. Djindjic 81 18000 Nis Biology Research Team Research Team Name Molecular Biology Individual Researcher No Research Team Leader Name Mrs., PhD Nadja Kokalj Vokač Contact Person Name Mrs., PhD Nadja Kokalj Vokaè Email [email protected] Function Professor of of Molecular Biology Phone + 386 2 321 10 00 Fax +386 2 331 23 93 Website http://www.sb-mb.si/index.php?id=12 Research Team Objectives Main Fields Biology Molecular Biology Partners/Interests researcher industrial partner Suitable Biology 1. STUDY OF TELOMER DYNAMICS AND HUMAN TELOMERASE GENE AMPLIFICATIONS IN PREINVASIVE LESIONS AND CANCER Research work in our laboratory of medical genetics is orientated on the problems of DNA copy numbers in human genome. Using different molecular ( MLPA : Multiplex Ligation-dependent Probe Amplification) and molecular cytogenetic techniques (FISH : fluorescent in situ hybridization and CGH : comparative genome hybridization) we are investigating amplifications, duplications and deletions in the genome related to mental retardation, contiguous genetic diseases, neuromuscular disorders and cancer. Our major interests are pre-invasive lesions and cancer. In nearest future we will focus on the problem of telomere dynamics. A reduction of telomeric DNA is responsible for genetic instability and could be an important factor in causation of predisposition to developed cancer. The measurement of telomere shortening as an early somatic DNA alteration could be useful diagnostic tool. Our project is to study the shortening of telomeres in different types of diseases which predispose to cancer (mielodisplastic diseases, cervical dysplasia). On the other hand activation of telomerase is also widely observed in human malignancies and is the most common mechanism through which cancer cells stabilize their telomere size. Amplification of TERC (human telomerase gene) was observed in various cancers. In our study we will use TERC gene as DNA FISH probe to detect gains of TERC gene as predictive marker for invasive carcinomas of cervical cancer and possible marker for other invasive carcinomas. New fused genes as a consequence of chromosome rearrangements are also known as crucial in cancer development. We are interested in one such gene TPRSS2 which fuse with ETS family members and play a role in prostate cancer. Its fusion most likely cause overexpression of ERG or ETV1 gene. The fused protein may also exist in other epithelial cancers. Combination of FISH and MLPA technique will be used in all our experiments. Finding significant markers in cancer predisposition and development and application of our results in diagnostics of cancer is a main goal of our research work. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Biology Research Team Research Team Name School of Dental Medicine University of Zagreb, Department of Dental Anthropology Individual Researcher No Research Team Leader Name Professor Hrvoje Brkic Research Team Members Team Member 0 Professor Ivana Cukovic-Bagic [[email protected]] Team Member 1 DDS, PhD Jelena Dumancic [[email protected]] Team Member 2 DDS, MD, Assistant Marin Vodanovic [[email protected]] Team Member 3 DDS,MD, Assistant Andrej Katalinic [] Team Member 4 DDS, PhD Miroslav Milicevic [[email protected]] Research Team Projects Project Name ANALYSIS OF TEETH IN IDENTIFICATION OF EXHUMED WAR VICTIMS IN CROATIA Project Leader Professor Hrvoje Brkic [[email protected]] Project Funding Agency Ministry of Science, Education and Sports Project Budget 10.000 € Project Start Date 2002-06-01 Project End Date 2006-05-01 Project Partners Project Summary Achievements of civilization in the past decades resulted with a worldwide increase in human mortality linked to mass disasters. For examples are numerous traffic accidents, especially the air ones, followed by wars and terrorist attacks of which the worse happened recently in the United States and resulted with loss of more than 4000 people. In order to act fast in such situations, forensic experts of all scientific and clinical disciplines need data for fast determination of identities of human remains. Teeth analysis is one of the basic procedures in the identitfication of unknown person. The reason lays in the high share of anorganic substance in the composition of teeth, which makes them the most solid and consequently most resistant part of the human body. Traces of dentist’s interventions on teeth compared by antemortem dental characteristics such as dental charts, x-rays, plaster casts and photographs and combined with their natural characteristics, make teeth unique and easy to be recognized by an eye of forensic expert. Apart from the use of their morphological recognizability, teeth are also used for different biological and biochemical researches in the forensic procedures for the determination of identity. The use of teeth and dental tissues in the identitfication procedures of human remains of war victims is therefore the aim of the research proposed in this document.Teeth, extracted from human remains, will be analysed through histological, biological and biochemical procedures for the purpose of the determinaton of victim’s age, sex and final confirmation of the identity by the analysis of the DNA from the dental cells. The results of this research will have their practical appliance in the procedures of the identification of human remains exhumed from the mass graves on the territory of Croatia. On the day of writing this project proposal it is a fact that still 1430 persons are being considered missing from the 1991 war in Croatia. It is expected that the gains of the three years work on the proposed project will be manifold: interdisciplinary approach of experts from different biomedical disciplines in the procedures of the analysis of teeth and dental tissues, significant contribution in scientific research to Croatian biomedicine, assistance to Croatian goverment in the procedures of identification of exhumed human remains of the 1991 war victims. Project Website http://zprojekti.mzos.hr/zprojektiold/arh_det Contact Person Name Professor Hrvoje Brkic Email [email protected] Function Vice Dean for International Cooperation Phone + 385 1 4802 123 Fax + 385 1 4802 159 Biology Website http://dental.sfzg.hr/~brkic Research Team Objectives Main Fields Biology Anatomy Dentristry Solid dental tissues are one of the longest lasting physical evidence after death. The clinical application of the human identity determination procedure through the analysis of teeth - after individual and mass disasters - is based on the scientific achivements and knowledge of all morphological, biological and biochemical characteristics of the teeth. According to the achieved results in this research, same methods will be applied for the determination of the identities of the living persons, as well as for the determination of the identities of the unknown human remains. They will also be used for the putting together of the dental profile on theosealo-dental samples of the archaeological material on the territory of the South Eastern Europe since the antique period. Partners/Interests researcher Anatomy Dentristry Biology Dentists, Anthropologists, Forensic experts Human dentition in forensic and archaelogical researches in South Eastern Europe Institution/University Name of Institution/University School of Dental Medicine Number of Employees 250 Number of Researchers 150 Country Croatia Postal Adress Gunduliceva 5 10 00 Zagreb Biology Research Team Research Team Name Section of Neurogenetics, Cytogenetics and Developmental Genetics Croatian Institute for Brain Research Individual Researcher No Research Team Leader Name Professor Srecko Gajovic Research Team Members Team Member 0 PhD student Anja Baresic [[email protected]] Team Member 1 MD Vesna Furic [[email protected]] Team Member 2 PhD Marija Curlin [[email protected]] Team Member 3 MD, PhD Dinko Mitrecic [[email protected]] Team Member 4 Assoc. Prof. Tatjana Belovari [[email protected]] Team Member 5 Professor Ljiljana Kostovic-Knezevic [[email protected]] Team Member 6 medical ing. Sandra Mavric [[email protected]] Team Member 7 medical ing. Iris Sumera [] Research Team Projects Project Name Gene function in differentiation and plasticity of mouse central nervous system Project Leader Professor Srecko Gajovic [[email protected]] Project Funding Agency Ministry of science Project Budget 50000 € Project Start Date 2007-01-01 Project End Date 2012-01-01 Project Partners Belgium/ULB/Lab of neuropathology Italy/ICGEB/Lab of mouse genetics Germany/U of Hanover/Developmental Biology Unit Project Summary Insight in mammalian gene function in vivo will be obtained through phenotype analysis of genetically modified mice. Molecular basis of differentiation and plasticity of the central nervous system will be investigated on 6 mouse mutants. Pax3 (Paired box gene 3) function will be assesed in splotch mice, which exhibit neural tube defects and spina bifida. Noto (Notochord homologue) function will be asessed in truncate (spontaneous mutation) and NotoGFP mice (knockout), which exhibit partial lack of notochord and disturbed differentiation of the neural tube. Stam2 (signal transducing adaptor molecule 2), Nol1 (nucleolar protein 1) and Klf8 (Krueppel like transcription factor 8) function will be assessed on mice obtained by gene trap method. This method involves random insertion of DNA vector, which monitors the expression of the mutated gene with lacZ as a marker, and in addition disturbes the production of the corresponding protein. Stam2 is involved in cell signaling through endocytic pathway, Nol1 is involved in ribosome biogenesis in nucleolus, and Klf8 is a transcription factor with unknown function related to mental retardation. In order to elucidate gene function in differentiation and plasticity of the central nervous system, Pax3 and Noto activity will be revealed in neuroectoderm differentiation through neurulation, during the closure of the posterior neuropore and in the pathogenesis of spina bifida. Stam2 function will be investigated in the neurons in relation to cell signaling connected with endosomal transport of cargo and membranes during differentiation and plasticity in the brain. Molecular characterization of the mouse mutants and expression pattern determination of the involved genes will serve as a prerequiste for the phenotype analysis. The central nervous system phenotype of developing and adult mutant mice will give insight in gene function in vivo. This approach will be complemented with experiments in vitro, which should disclose the molecular and cellular basis of the observed changes. This will reveal not only the consequences of genetic change on the system level, but as well on the cellular level. Therefore the implications of the proposed reasearch cover genetic basis of human brain diseases, but as well basic understanding of the gene activity and regulation during differentiation and plasticity in the central nervous system. Project Website Contact Person Name Professor Srecko Gajovic Email [email protected] Biology Function Head of Section Phone +385 1 4596 829 Fax +385 1 4596 942 Website neurogenetika.hiim.hr Research Team Objectives Main Fields Biology Genetics Cytology Our main aim is to understand gene function in the mouse nervous system using mouse mutants. Currently we concentrate on Stam2 gene, which is involved in endosome mediated cell signaling, important for function of synapse, retrograde axonal signalling and dendrite remodelling. Partners/Interests researcher Biology Genetics Cytology Neuroscience, neuroimagining, phenotyping of mouse brain Signaling pathways in the neurons are in the basis of neurodegeneration and repair. The signaling pathways interconnection with membrane transport is poorly understood, but could be crucial for neurons, which exhibit an intense transfer of both membranes and informations. Institution/University Name of Institution/University School of Medicine University of Zagreb Number of Employees 400 Number of Researchers 200 Country Croatia Postal Adress Salata 3 10000 Zagreb Biology Research Team Research Team Name University of Osijek School of Medicine DNA Laboratory Individual Researcher No Research Team Leader Name Dr. Gordan Lauc Research Team Projects Project Name Glycosylation and Human Lectins in Rheumatoid Disease Project Leader prof. Yuan C. Lee [[email protected]] Project Funding Agency NIH Project Budget 148000 € Project Start Date 0000-00-00 Project End Date 0000-00-00 Project Partners USA / Johns Hopkins University / Biology Department Croatia / University of Zagreb Faculty of Pharmacy and Biochemistry Project Summary Project Name Glycogold: Exploration of the nature and potential of Glyconano-particles Project Leader . J.F.G. Vliegenthart [.@.] Project Funding Agency FP6 Project Budget 5000000 € Project Start Date 0000-00-00 Project End Date 0000-00-00 Project Partners Project Summary Project Website Contact Person Name Dr. Gordan Lauc Email [email protected] Function Professor of Biochemistry and Molecular Biology Phone +385 31 512 865 Fax +385 31 505 615 Website biochem.mefos.hr Research Team Objectives Main Fields Biology Biochemistry Genetics Molecular glycobiology of pathobiochemical processes Partners/Interests researcher Biochemistry Biology Genetics Institution/University Name of Institution/University University of Osijek School of Medicine Number of Employees 100 Number of Researchers 70 Country Croatia Postal Adress J. Huttlera 4 31000 Osijek Biophysics Research Team Research Team Name Biophysics Individual Researcher No Research Team Leader Name Mr., PhD Milan Brumen Contact Person Name Mr., PhD Milan Brumen Email [email protected] Function Professor of Biophysics Phone + 386 2 234 56 01 Fax + 386 2 234 56 00 Website www.uni-mb.si Research Team Objectives Main Fields Biophysics Partners/Interests researcher industrial partner Suitable Biophysics 1. BIOPHYSICS OF CALCIUM SIGNALLING AND FORCE GENERATION IN AIRWAY SMOOTH MUSCLE CELLS We are studying the calcium signaling pathway in airway smooth muscle cells from oscillations of cytosolic calcium concentration to force generation in muscles. The method applied is mathematical modeling. In particular, our studies are focused to interactions of calcium with calcium binding proteins and relation between myosin phosphorylation and force development. Recently we published the mathematical model of a detailed kinetic scheme describing interactions between Ca2+, calmodulin (CaM) and myosin light chain kinase (MLCK), yielding eight different aggregates [1]. The important result of the model is the prediction of Ca2+ dependent active form of MLCK which is in the model taken as proportional to the concentration of Ca4CaM×MLCK complex. It presents a significant progress in the modelling of these interactions. Based on this model we intend to extend our theoretical studies to modelling Ca2+/CaM dependent MLCK activation in the presence of myosin as the substrate for MLCK whereby phosphorylation and dephosphorylation of myosin is taken into account. This step in modelling enables the prediction of MLCK activity and, thus, comparison to a much broader set of available experimental data for MLCK activity and its relation to myosin phosphorylation. The model will be analyzed by applying the control theory for sensitivity of the main system variables such as myosin phosphorylation. The emphasis is given to the influence of elevated total concentration of MLCK, the property of bronchial muscle cells obtained from asthmatic subjects [2]. The model predictions will be directed to MLCK activation under physiological conditions. The elevated MLCK should affect the myosin phosphorylation and, hence, the magnitude of force. It is important also to study the time dependent response of MLCK activation with respect to calcium oscillations especially in the range of physiologically significant low cytosolic Ca2+ concentrations. It is desirable to build a link to a laboratory which has interest in collaborating in these topics and could perform accompanied experiments. In the project proposed other signalling calcium dependent and independent pathways can be studied from the point of view of their role in activities of MLC kinase and phosphatase as well as in force generation. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Biophysics Research Team Research Team Name Center for laser microscopy; Sch of Biology; Univ. of Belgrade Individual Researcher No Research Team Leader Name professor Pavle Andjus Research Team Members Team Member 0 PhD Biljana Božić [[email protected]] Team Member 1 B.Sc. Nebojša Jasnić [[email protected]] Team Member 2 MSc Aleksandar Bajić [[email protected]] Team Member 3 professor Pavle Andjus [[email protected]] Research Team Projects Project Name Biophysical neuroprofiling on experimental models of damage and repair in CNS Project Leader prof. Pavle Andjus [[email protected]] Project Funding Agency Ministry of Science Rep Serbia Project Budget 87000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Serbia/Univ. of Belgrade/School of Biology Serbia/Univ. of Belgrade/ Inst. for Biol. Res. "Siniša Stanković" Serbia/Univ of Belgrade/School of Medicine Serbia/Univ. of Belgrade/School of Physical Chemistry Belgium/Universite Libre de Bruxelles/School of Medicine USA/Mayo Clinic, Rochester Project Summary Experimental models of CNS damage will be studied through the employment and development of modern biophysical techniques -laser scanning confocal microscopy, electrophysiology ( «patchclamp»)and in vivo NMR. These techniques in synergy will be used to reach the basic conditions for the formation of neurophysiological and biophysical profiles –«neuroprofiles» of cells and tissues in the state of unbalanced homeostasis.The studies models will include: a) amyotrophic lateral sclerosis (ALS)-primary cell cultures of neurones and/ or glia treated with purfied fractions of patient CSF and sera, as well as rats with mutant CuZn superoxide dismutase;b) experimental allergic encephalomyelitis a model of multiple sclerosis - will also serve for a comparative study (vs. ALS) of underlying autoimmune mechanisms ; c) transgenic mice deficient in the proteoglycan tenascin - for the study of molecular mechanisms of synaptic restoration. The expected results will put lihgt on the role of postsynaptic receptors and glutamate transporters, on the significance of oxidative stress and calcium homeostasis, on the intercellular connections of neurons and glia, with emphasis to the role of glia, in the processes of injury, healing, and recovery. Neuroprofiling will be used to define inflammatory lesions. Neuroprofiles should facilitate a closer definition of mechanisms of disease and repair, more precise and specific diagnostics, and a more reliable introduction of therapeutic agents. Project Website Research Team Projects Project Name REINFORCING A CENTRE FOR LASER MICROSCOPY AND CELL PROFILING FOR REGIONAL NETWORKING Project Leader prof. Pavle Andjus [[email protected]] Project Funding Agency EC FP6 & Minist. of Sci Rep. of Serbia Project Budget 500000 € Project Start Date 2006-06-01 Project End Date 2009-05-31 Project Partners Serbia/Univ. of Belgrade/ Sch. of Biology Croatia/Univ. of Zagreb/ Sch. of Medicine Italy/Univ. of Turin/Dept. of Neuroscience Italy/CNR/Inst. of Neuroscience, Pisa Norway/Univ of Oslo/Ctr for Mol Biol and Neuroscience Slovenia/Univ. of Ljubljana/Sch. of Medicine Biophysics Project Summary The main objective of the proposal is to improve research capacities of a Western Balkan (WB) research centre and of WBs in general, for the groundbreaking research field of cell and tissue imaging in life sciences for health, particularly neurosciences and neurology. The WB centre, which is the single proposer of this action, will be the Institute for Physiology and Biochemistry, School of Biology, University of Belgrade with its Centre for laser microscopy. In addition to diverse resources for neuroscience and physiology, the Institute is equipped with a laser scanning confocal microscope that will present the core facility for the project research management. The principal objective will be met through a work plan designed to 1) develop the confocal imaging core platform taking into account specific scientific directions, i.e. physiology time-series and plasticity. development and molecular genetics, 2) increase the capacity to participate in the research programmes of the EU and to improve already existing links with well-established European research centres via intense networking, 3) strengthen the technical capacity by upgrading and maintenance of equipment and by provision of key skills, employment of young researchers and exchange visits of scientists, 4) bridge the gap between theoretical and applied science and serve the socio-economic needs of the country by supporting medical and pharmaceutical research through interaction with medical institutions, 5) disseminate knowledge of cell imaging beyond the field of neuroscience and forming a wide regional database of potential users and collaborators. Project Website http://clm.bio.bg.ac.yu Contact Person Name professor Pavle Andjus Email [email protected] Function vice dean for science Phone +381-11-3032356 Fax +381-11-2638500 Website bio.bg.ac.yu Research Team Objectives Main Fields Biophysics Physiology Cytology Study of ion transport, synaptic plasticity and repair in experimental models of neurodegenerative diseases by imaging and electrophysiology Partners/Interests researcher experimental neurologist electrophysiologist expert on Neurology Biophysics Physiology experimental neurologist electrophysiologist expert on motoneuronal and related diseases and repair expert on neuroimaging (MRI) on small animals expert on intracellular ion imaging expert on confocal microscopy Role of extracellular matrix (ECM) in neuroregeneration and neural plasticity. Glia-Neuron interaction in brain repair and calcium-signalling. Nanoparticles for neuraltherapy Institution/University Name of Institution/University School of Biology University of Belgrade Number of Employees 170 Number of Researchers 74 Country Serbia and Montenegro Postal Adress Studentski trg 12 11000 Belgrade Clinical Chemistry Research Team Research Team Name Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb Individual Researcher No Research Team Leader Name Prof. dr. sc. Tihana Zanic Grubisic Research Team Members Team Member 0 Prof. dr. sc. Ivana Cepelak [[email protected]] Team Member 1 Prof. dr. sc. Karmela Barisic [[email protected]] Team Member 2 Assist. Prof. dr. sc Lada Rumora [[email protected]] Team Member 3 Assist. Prof. dr.sc. Jozsef Petrik [[email protected]] Team Member 4 Assist.Prof.dr.sc. Roberta Petlevski [[email protected]] Team Member 5 Research assistant Marija Grdic [[email protected]] Contact Person Name Prof. dr. sc. Tihana Zanic Grubisic Email [email protected] Function Head of the Department for Medical Biochemistry and Haematology, Phone 385 1 46 12 606 Fax 385 1 46 12 716 Website pharma.hr Research Team Objectives Main Fields Clinical chemistry Biochemistry During the last decade, attention was oriented towards mechanisms of the cellular defence in the development of complications in the chronic diseases, in particular toxic nephropathy and Balkan endemic nephropathy. Currently, we are studying metabolic complications in COPD and mechanisms of pulmonary cell destruction through activation of apoptosis. It is anticipated that apoptotic signalling pathway involves activation of MAPK, heat shock proteins, redox-sensitive transcription factors NFkappaB, activator-protein-1 (AP-1), cytokines IL-6 and IL-8 and other inflammatory mediators. We plan to select new markers that will be tested in COPD patients classified according to GOLD standard. Involvement of systemic inflammation, cardiovascular effects, osteoskeletal effects, metabolism of muscle proteins will be followed in COPD patients by using samples obtained by noninvasive methods – blood serum, cells and expired breathe condensate. The main goal of this study is to describe optimal combination of relevant biochemical markers that could be used for diagnosis and progression of COPD, differential diagnosis related to other respiratory diseases, therapy monitoring and evaluating selected targets that could be used for the therapeutic purposes. Partners/Interests researcher Biochemistry Clinical chemistry We seak partners capable of participating in the high throughput analytical analyisis needed for metabolomic studies. We are also interested in analysis of expired breath condensate, since we only started with that kind of studies. We are interested to further continue on folowing metabolic changes, by means of accquiring metabolomics data in COPD, since there is evidence that metabolic changes in the mucsles are developing with thw progression of the disease. Institution/University Name of Institution/University Faculty of Pharmacy and Biochemistry, University of Zagreb Number of Employees 8000 Number of Researchers 2000 Country Croatia Postal Adress A. Kovacica 1 10000 Zagreb Clinical Microbiology Research Team Research Team Name Department of Virology, Institute of Microbiology and Immunology, School of Medicine, University of Belgrade Individual Researcher No Research Team Leader Name Professor Tanja Jovanovic Research Team Members Team Member 0 Professor Maja Cupic [[email protected]] Team Member 1 Teaching assistant Aleksandra Knezevic [[email protected]] Team Member 2 Teaching assistant Maja Stanojevic [[email protected]] Team Member 3 Teaching assistant Ivana Lazarevic [[email protected]] Team Member 4 Professor Tanja Jovanovic [[email protected]] Research Team Projects Project Name Biological Consequences of Viral Genetic Variability Project Leader Professor Tanja Jovanovic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary Genetic variability is one of the intrinsic properties of viruses, resulting in heterogenecity of viral genotypes. It is mostly due to point mutations of viral nucleic acid that can affect biological properties of viruses in a number of ways: by altering viral virulence, by modifying "fitness", by inducing escape from host immune defences or resistance to antivirals. Primary resistance is an emerging problem in antiviral therapy, since patients infected with drug resistant virus may experience a less efficient viral response to therapy. Molecular epidemiology and distribution of viral genotypes, as well as frequency and nature of antiviral resistance in our population is largely unknown, for the majority of viruses. Our study includes molecular analysis, genotypic and phenotypic characterization of viruses inducing persistant infections (herpes viruses - CMV, HSV, EBV etc; human papillomaviruses; HIV), hepatitis viruses B and C and influenza virus. Thus, our study will provide the firs molecular analysis locally, giving basic insight in molecular epidemiology of studies viruses and resistance to antivirals in our population. Our results will contribute to development of strategies for optimal use of antiviral treatments. Project Website Contact Person Name professor Tanja Jovanovic Email [email protected] Function Head of virology department of the Institute of microbiology Phone 381 11 656 950 Fax 381 11 2685 584 Website med.bg.ac.yu Research Team Objectives Main Fields Clinical microbiology Team's research interests: HIV resistance patterns in treated and untreated patients and correlation to treatment; HBV and HCV genotyping, correlation of genotype to clinical manifestations and mapping of resistance-associated mutations; HPV prevalence and genotyping; CMV genotyping and mapping of resistance-associated mutations in immunocompromised hosts and in perinatal infections; genotypic and phenotypic patterns of HSV resistance Partners/Interests researcher Clinical microbiology Epidemiology Clinical Microbiology Researcher in the field of clinical virology with skills and laboratory equipment for amplification, quantitation and genetic analysis of viral nucleic acids First insight in molecular epidemiology and resistance to antivirals in Serbia and other countries in the region (HIV, HBV, HCV, HPV, herpesviruses, influenza virus) - genotype distribution and specific mutants of HBV, expanding existig data on HCV heterogeneity, presence and spread of CMV genotypes, presence and characteristics of HSV resistance to antivirals (particularly acyclovir), heterogeneity and phylogenetic characteristics of HPV genotypes, HIV resistant patterns in treated and untreated patients and correlation to treatment Institution/University Name of Institution/University School og Medicine, University of Belgrade Number of Employees 1000 Number of Researchers 850 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgarde Cytology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Prof. Zoran Milosavljevic Research Team Projects Project Name Forming the Living skin equvivalent and examination of its histological, immunohistochemical and biomechanical characteristics Project Leader Prof Zoran Milosavljevic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-01-01 Project End Date 2003-12-31 Project Partners Project Summary Project was aimed to reveal the cost-effective methodology for reconstructing the living skin equvivalent in cell culture conditions. Examination of LSE histological and biomechanical characteristics was also planned. Project Website Project Name Influence of various growth factors, hormones and cytokines of biological behaviour of the cultivated human keratinocytes Project Leader Prof Zoran Milosavljevic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-08-31 Project End Date 2008-01-01 Project Partners University Pristina, Medical School Kosovska Mitrovicy Project Summary Project is aimed to reveal the effects of examined factors on biological behaviour of the cultivated human keratinocytes Project Website Contact Person Name prof zoran milosavljevic Email [email protected] Function Head of Histology and Embryology Dept Phone + 381 64 124 74 61 Fax + 381 34 306 800 Website www.medf.kg.ac.yu Research Team Objectives Main Fields Cytology Biology Cytology tissue engineering, histology, immunocytochemistry, cell culture Partners/Interests researcher Biology Pharmacy Other allied sciences Skin cultivation expertise, dermatology or plastic surgery specialty Project should be aimed to reveal cost-effective and biologically safe way to obtain large quantities of Cytology cultivated human epidemis or living skin equvivalent in order to improve treatment options for the patients with large skin deffects Institution/University Name of Institution/University University Kragujevac Medical Faculty Number of Employees 200 Number of Researchers 100 Country Serbia and Montenegro Postal Adress Svetozara Markovica 69 34000 Kragujevac Cytology Research Team Research Team Name "Functional morphology of thymus and spleen" Individual Researcher No Research Team Leader Name Prof. Dr. Novica Milicevic Research Team Members Team Member 0 Dr. Milica Labudovic-Borovic [[email protected]] Team Member 1 Prof. Dr. Zivana Milicevic [[email protected]] Research Team Projects Project Name Homeostatic control of structural integrity and size of lymphatic organs Project Leader Prof. Dr. Novica Milicevic [[email protected]] Project Funding Agency Ministry of Science of Republic of Serbia Project Budget 25.000 € Project Start Date 2006-10-01 Project End Date 2010-12-31 Project Partners Germany, University of Lübeck, Institute of Anatomy Project Summary Lymphotoxin-beta receptor (LTBR) signaling pathway has a crucial role in biogenesis of peripheral lymphatic organs (PLO). Its disruption induces a profound disturbance of PLO development: Peyer patches and lymph nodes are lacking, the splenic white pulp is disorganized. Recently, indications appeared suggestive of role for LTBR in maintenance of structural integrity of PLO. However, in these studies the complex methods were used and ambiguous results were obtained: the developmental and homeostatic mechanisms could not be clearly discerned. Finally, the works dealing with homeostatic control of PLO size are unusually rare. On the other hand, very recent studies have shown that LTBR axis also influences the function of central lymphatic organs, i.e., the thymus. This signaling pathway controls the activity of AIRE transcription factor, which is indispensable for proper negative selection and suppression of autoimmunity. However, the data on structure of LTBR deficient thymus are exceptionally few and the identity of thymic AIRE-expressing cells is not indisputably determined. Therefore, our aim is to study: (A) the role of LTBR axis in maintenance of PLO structure and control of PLO size in the adult organism using regeneration of splenic implants as a straightforward and reliable model, (B) the role of LTBR axis in establishing and maintenance of thymic structure using morpho-functional approach. Flow cytometry, immunocytochemistry and selected in vitro methods will be used. Project Website Contact Person Name Prof. Dr. Novica Milicevic Email [email protected] Function Full Professor Phone +381-11-3615-772 Fax +381-11-3612-567 Website med.bg.ac.yu Research Team Objectives Main Fields Cytology Anatomy Immunology and Immunohaematology Functional morphology of the organs of the human and rodent immune system. Cellular and structural organization of the thymus and spleen in normal and pathological conditions: after application of toxic, cytostatic and immunomodulatory substances, after removal/absence of the thymus or spleen, as well as in tumor necrosis factor- and lymphotoxin beta receptor-deficient animals. Partners/Interests researcher Immunology and Immunohaematology Cytology Cytology -animal facility with barrier for breeding of genetically manipulated animals -cytological facilities (tissue culture, flow cytometry, immunocytochemistry, in situ hybridisation) -microscopical facilities (light, confocal, EM) -immunological facilities -molecular biology (PCR, western blotting, immunoprecipitation) My interest is particularly directed towards a special type of thymic nonlymphocyte cells – thymic metallophilic macrophages – that we carefully studied for many years (Milićević NM, Milićević Ž. Thymus cell-cell interactions. Int Rev Cytol 235:1-52, 2004). These cells are strategically positioned between the cortex and medulla, forming a distinct row in the cortico-medullary zone of the rat thymus, and show a number of characteristic features. Metallophilic macrophages seem to be involved in thymocyte maturation: they promptly respond to the damage caused by toxic agents and their reactivity is neatly coordinated with the subsequent thymus regeneration. Metallophilic macrophages have overdeveloped specialized endocytic compartments for the processing and presentation of antigens by major histocompatibility complex (MHC) class II molecules. These cells undergo dramatic changes, if negative selection is blocked by cyclosporine A. All this suggests that thymic metallophilic macrophages could be involved in clonal deletion of thymocytes. Therefore, I would like to investigate this issue using various approaches: i) in vitro isolation of these cells and testing their capacity to uptake and present antigens, ii) in vivo capability to uptake and present antigens and iii) their reactivity in animal models of disrupted or enhanced negative selection. In a broader context, I am interested in all aspects of studies related with the control of thymocytopoiesis and negative selection in the thymus Institution/University Name of Institution/University Inst. of Histology, Fac. of Medicine, Univ. of Beograd Number of Employees n.a. Number of Researchers n.a. Country Serbia and Montenegro Postal Adress Visegradska 26 11000 Beograd Dentistry Research Team Research Team Name Project recognized from ministry of Science, Croatia: "influence of prosthodontic appliance to orofacial system and health" Individual Researcher No Research Team Leader Name Prof. PhD. Asja Celebic Research Team Members Team Member 0 mr.sc. Igor Stipetic [] Team Member 1 Doc.PhD. Danijela Kovacevic [] Team Member 2 mr.sc.dr. Ivan Kovacic [[email protected]] Team Member 3 Prof.PhD. Senka Mestrovic [[email protected]] Team Member 4 Mr.sc. Milan Papic [[email protected]] Team Member 5 PhD. Renata Poljak Guberina [[email protected]] Team Member 6 Mr.sc.dr. Maja Baucic Bozic [[email protected]] Team Member 7 Prof.PhD. Jasmina Stipetic [[email protected]] Team Member 8 Prof.PhD. Ivo Baucic [[email protected]] Team Member 9 Mr.sc.dr. Nikola Petrièeviæ [[email protected]] Team Member 10 doc.PhD. Dubravka Knezovic Zlataric [[email protected]] Team Member 11 PhD. Ivan Kovacic [[email protected]] Team Member 12 Prof.PhD. Senka Mestrovic [[email protected]] Team Member 13 PhD. Renata Poljak-Guberina [[email protected]] Team Member 14 Prof.PhD. Ivo Baucic [[email protected]] Team Member 15 Higher Lect., Mr.sc. Milan Papic [[email protected]] Team Member 16 Mr.sc. (Assistant) Maja Baucic-Bozic [[email protected]] Team Member 17 Doc.PhD. (Ass.Prof.) Dubravka Knezovic Zlataric [[email protected]] Team Member 18 Prof.PhD. Jasmina Stipetic [[email protected]] Team Member 19 Mr.sc. (Assistant) Nikola Petricevic [[email protected]] Team Member 20 Prof.PhD. Asja Celebic [[email protected]] Contact Person Name Prof. PhD. Asja Celebic Email [email protected] Function Full Professor at the Department for Prosthodontics Phone +38514802165 Fax +38514802159 Website sfzg.hr Research Team Objectives Main Fields Dentristry Oral health and prosthodontic appliance Partners/Interests Dentristry Institution/University Name of Institution/University School of dental medicine, University of Zagreb Number of Employees 150 Number of Researchers 60 Country Croatia Postal Adress Gunduliceva 5 10000 Zagreb Dentistry Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MSc Nedeljka Ivkovic Research Team Members Team Member 0 assistent Irena Mladenovic [[email protected]] Team Member 1 Senior assistent Nedeljka Ivkovic [[email protected]] Contact Person Name MSc Nedeljka Ivkovic Email [email protected] Function Senior assistent Phone +38765224664 Fax +38756210171 Website www.medfak.srbinje.net Research Team Objectives Main Fields Dentristry Prosthodontics as well as gnatology Partners/Interests researcher Dentristry Biochemistry I would like to find partner,researcher, who has also investigeted in field of gnathology, it means, nature and artificial occlusion, functions and dysfunctions of masticatory system Temporomandibular disorders (TMD) are loosely defined as an assorted set of clinical conditions, characterized by pain and dysfunction of the masticatory system. Extensive literature suggests the disoreds is 1,5-2 times more prevalent in women than in man, and 80%of patient treted for TMD are women. The severity od symptoms is also related to the age of patients.Pain onset tends to occure after puberty, and peaks in the reproductive years, with the highest prevalence occuring in women aged 20-40, and the lowest among children, adolescent, and the elderly.The gender and age distribution of TMD suggests a possible link between its pathogenesis and female hormonal axis. The aim of investigation would be to examine the role hormones in TMD Institution/University Name of Institution/University University of East Sarajevo, Faculty of Dentistry Number of Employees 50 Number of Researchers 20 Country Bosnia-Herzegovina Postal Adress Studentska bb 73300 Foca Dentistry Research Team Research Team Name Department of Endodontics and restorative Dentistry Individual Researcher No Research Team Leader Name Prof.dr. Ivica Anic Research Team Members Team Member 0 prof.dr. Nada Galic [] Team Member 1 prof.dr. Greta Staudt-Skaljac [] Team Member 2 dr. stom Zoran Karlovic [] Team Member 3 prof.dr. Bozidar Pavelic [[email protected]] Team Member 4 doc.dr. Silvana Jukic-Krmek [[email protected]] Team Member 5 dr.stom Josipa Borcic [] Team Member 6 prof.dr. Sanja Segovic [[email protected]] Team Member 7 prof.dr. Ivana Miletic-Karlovic [[email protected]] Contact Person Name Prof.dr. Ivica Anic Email [email protected] Function Head of Department Phone 0038514802116 Fax 0038514802159 Website sfzg.hr Research Team Objectives Main Fields Dentristry Clinical microbiology Epidemiology Epidemiological testing of appearance of dilacerations, osteosclerotic and radiolucent changes will be conducted on 2000 orthopantomograms of Zagreb's population patients. The criteria for determining idiopatic osteosclerotic lesion would be a well defined shadow bigger than three mm of a spherical or eliptic shape without surrounding radiolucent edge. All the others shadows with specific diagnosis would be excluded from work. In statistical analysis parametric or nonparametric tests will be applied depending on the distribution of obtained results. One hundred samples of mandible obtained from Institue of Anatomy and Institute of Forensic Medicine will be used to study mandibular foramen: the cavity size, the existence of lingua and antilingua, the distance from the lower edge od ascending part; the distance according to the vertical from chewing bevels as well as the difference in constitution and position of left and right side of the jaw. The following will be examined for the mental foramen: size and position, the distance from the lower edge of the jaw, distance from the mandibular angle, the distance between protuberantie mentalis and the ascending part of the mandible and the difference in size and position between left and right size of the jaw. The leakage of materials for retrograde filling will be examined by the solution for leakage assesment (bovine serum albumin) with root end resection under the angle of 45 and 90°. While assesing the concentration of leaked protein molecules (bovine serum albumin) the Bradford method of protein quantification is applied. In Bradford method the protein reagent is represented by Coomassie Brilliant Blue G dye in acidic solution. The absorption maximum of Coomassie Brilliant Blue G is moved form 465 nm to 595 nm when binding with a protein. Absorption is directly proportional to the concentration and when determining it, spectrophotometer with the maximal transmission on 595 nm is used. The activity of apoptotic genes after the contact with examined materials will be determined by Western Blot Method. The induction of apoptosis will be observed by determining the number of cells with characteristic morphological changes using the fluorescent microscope. The fragmentation of DNA (as the proof of apoptosis induction) will be determined after the isolation of DNA with the standard method on the agarose gel. As contol samples the same cell cultures and procedures will be used but instead of the examined materials they will be treated with the physiological solvent. All experiments will be repeated three times. Mutagenicity will be tested by two standard cytogenetic procedures: analysis of the structural chromosome aberration and micronucleus test. Both procedures will be conducted on the cultures of human peripheral blood lymphocite. The antibacterial effect of root canal filling materials based on silicone, composite, zinc-oxide and epoxy resin will be examined by direct contact test (DCT). During the endodontic treatment a sample from a root canal will be taken from 40 Dentistry patients with the primary infection of root canal, clinicallly and rtg diagnosed symptomatic acute and asymptomatic chronic apical lesions. These samples will be submitted to DNA analysis (PCR dignostics) at Ruðer Boškoviæ Institute. The patients of both sexes, aged eighteen to sixty-five would be included. The sample would be taken from single root and multi-rooted teeth. With the upper molars the sample is taken from palatinal root canal while with the lower molars the sample is taken from the distal root canal. The teeth will be isolated by coffer-dam, cleaned with 3% solution of hydro-peroxide, then with 2.5% water solution od natrium hypoclorite and the 5% solution of natritiosulphate. After the trepanation of a pulp chamber, the samples from the root canal will be taken with K reamer and with two sterile paper points. The points are left in the root canal for a minute and are put into the sterile tube for transport. The obtained sample will be prepared for PCR identification. Patients with the rtg diagnostic periapical lesion while being endodontically treated, will have root canals filled with the preparation based on calcium hydroxide and iontophoresis will be conducted. After the end of the treatment, after six months and after one year there will be rtg control and by densitometrics the fomation of soft tissue will be assessed. After the instrumentation of the root canal, sterilization of samples and artificial inoculation by standardized sort, there will be the disinfection of canals using RinsoEndo technique, ultrasonic and classical ways of root canal irrigation. After the experiment, the possibility of surviving and the number of inocular bacterias from root canals will be observed by microbiological techniques. The ability of releasing calcium and hydroxil ions from various preparations of calcium hydroxide (ready commercial preparations of various groups) will be determined by complexometric titration and by measuring pH with pH meter Scott. As the additional procedure of measuring ions the measuring of solution conductivity will be used. After the endodontic filling and cementing od glass posts by various cements (zinc-phosphate, composite and glassionomer cements) and the cyclic load the microlekage of root canal system will be examined by fluid transport model on 65 human incisors in vitro. In odontogenic cysts the expression of Fragile Histidine Triad (FHIT), tumor suppressor gene, will be tested on 3p14.2 locus, by immunohystochemical method. Anti-FHIT policlone antibody will be used as well visualisation reagent (biotinised antibody and streptavidin conjugated with peroxidas). In establishing the possible loss of heterozigocity by PCR method, the morphogenic polymorphe markers will be used (D3S1300, D3S4103). By pathohystologic tests the variability of odontogenic cysts constitution will be examined. The study in laser application will determine the vibration of teeth which is a consequence of lightening the tooth with various laser radiation energies. The vibrations during cavity restoration on the hard dental tissues caused by laser will be determined by Piezoelectric accelerometer, also on the soft tissues during operation and on the experimental model of hard and soft dental tissues. The turning moment should be measured as well as the axial/vertical force during root canal instrumentation by the following techniques: step-back, crown-down pressurreless, balanced force technique, ProFile and ProTaper. Also, it should be determined which force and turning moment will cause fissure or vertical fracture of the treated root. The distribution of forces occuring during instrumentation and filling of root canals on extracted teeth will be tested on the model of upper premolar by the finite element method. It will also be determined whether the obtained values leading to the fracture of root wall are backed by simulation on the tooth model. The following should also be determined: the direction of the strongest force impact on a particular root canal wall, pressure and tensile strain during instrumentation and root canal filling. The power of force during instrumentation will be measured by specially constructed device. The influence of the commercial preparation for bleaching (carbamid peroxide) to the vital pulp will be tested. The treated teeth will be premolars taken out of orthodontic reasons according to the plan of therapy. After the extraction the pulp undergoes pathohystological examination. The testings that are conducted on biolgical material (microorganisms, HeLa cells, fibroblasts) and the research on the material leakage begin in the first year of the project and continue all throughout the project because of the time requirements. The measuring of root canal filling materials leakage is repeated after one year. For epidemiological studies are also a continuation of the previous project and will continue for the first three years of work. The estimated time for biochemical testings on the loss of heterozygosity of FHIT tumor suppressor gene with various odontogenic cysts is three years. Physiochemical testings will be conducted during the whole project (three to five years). The continuous measuring od force that appears during manual and mehanical instrumentation and the laser work and drills attached to turbine extensions will be conducted throughout two years. The testing of root canal filling leakage before and after the preparation of post for nonmetal intracanal restoration will last for about a year and a half and is the continuation of work from the previous project. The measuring of vibration and noise is the continuation of the work on the project and is meant to continue in the following two years. The testing of disinfectant efficiency, iontophoresis and RinoEndo instruments will be conducted throughtout three years. The measuring of the turning moment and axial force during instrumentation and the value of forces tested by the finite element method will last for about three and a half years. The testings in writing Master's thesis paper usually last two to three years while those having a disertation as a goal last for three to five years. The duration estimate for the testing of tooth pulp pathohystiological changes under the tooth bleaching materials is two and a half year. Dentistry Partners/Interests researcher Dentristry Clinical microbiology Epidemiology We are seeking for reseatrches who would like to work or have previous experience in field of endodontics, periodontology or orthhodontics (materials, biocompatibility, microbiology, imunology, laser in dentistry). The appearance of dilacerations, condensing ostitis and idiopatic osteosclerosis of mandible and maxilla among Zagreb's population in relation to endodontic treatment will be assessed on 1000 orthopantomograms as well as the relation of the changes to age, sex, area and a jaw. The quality of endodontic treatment and the appearance of pathological changes will be assessed on 1000 orthopantograms of Rijeka's population. The anthropological measurements will be conducted on 100 samples of mandible. When studying the mandibular foramen the following will be observed: foramen size, the existence of lingua and antilingua, the distance from anterior and posterior edge of ramus; the distance from the lower edge of ramus and the incision between articular and muscular part, vertical distance from occlusal surfaces and of dental arch as well as the differences in the constitution and position of a particular foramen. The following will be examined for the mental foramen: size and position, the distance from the lower edge of the jaw; distance from the upper edge-with complete jaws the distance from occlusive surfaces; the distance from protuberantia mentalis and the ramus of mandible. The study on the effectiveness of iontophoresis will be carried out on the patients who have symptomatic or asymptomatic necrosis of tooth pulp with periapical pathosis. With the patients of the control group classical treatment procedure will be conducted while in the experimental group iontophoresis will be applied. For microbiological testing during endodontic treatment of the patients with the primary infection of root canals, with clinically and rtg diagnosed symptomatic acute and asymptomatic chronical periapical lesions, the sample from the root canal will be taken and submitted to DNA analysis (PCR). The patients of both sexes, aged 18 to 65 will be included. To determine the effectiveness of bleaching materials there will be an investigation on healthy teeth meant to be extracted from orthodontic reasons and the written confirmation by the patients themselves or the patient’s guardian will be required. The bleaching will be conducted using 6% carbamide peroxide for a period of one week according to the manufacturer instructions. The material will be applied with a brush in such a way that one tooth will be covered while the tooth on the opposite side of the jaw will be a control tooth. The tooth is extracted for orthodontic reasons immediately after the end of the therapy. The study results will provide data on the impact of carbamide peroxide on the tooth pulp. Biocompatibility of root canal filling materials will be examined by in vitro and in vivo procedures. In vitro procedures will be conducted on standardized cells. In vivo procedures will be carried out on laboratory rats that will be anaesthetized and the material will be implanted into subcutaneous tissue. The number, kind and position of inflammatory cells will be investigated throughout seven and thirty days. The reaction of bone tissue will be tested using the silicone tubes that will be implanted into the rat's bones (tibia). After 60 days the histological and hystomorphometric analysis will be done. The endodontic materials will be tested on adheration, fagocitosis and microbicide activity of macrophage. The sealing ability of the same materials will be tested by bacterial leakage test and fluid transport model. The investigation will be conducted after the periods of six months, one year and two years. The clinical studies will include the assessment of changes on the oral mucous membrane in relation to the homogeneity of restorative and prosthodontic materials among the senior citizens in Rijeka. The microbiological analysis of clinical samples from oral cavity will be done. Candida species isolated from clinical material up to the level of layer will be identified and the resistance of Candida species to dental materials will be determined. The impact of dental materials to macrophages will be investigated in in vivo conditions on experimental BALB/c mouses. The immunological reaction of tissue to materials and secretion of proinflammatory factors in supernatant of primary and continuous cell cultures infected by characteristic bacterial isolates will be investigated. The level of TNF-alpha and interleukins will be determined by commercial EIA kit. The persons included in the epidemiological studies of periodontal will be those above 30 years of age, of both sexes grouped according to age. The first group will include those with cardiovascular problems and they will fall into three subgroups: with arterial hypertension, with ischemic heart disease, those suffering from peripheral blood vessel disease. During the study it will be possible to group them into smaller subgroups (eg. those suffering from ischemic heart disease could be put into subgroups with angina pectoris and subgroups with myocardial infarction). The second group will include the patients with lung diseases and conditions. The third group will include the patients suffering from asthma, especially those under corticosteroid therapy. Disease duration will be determined for each patient. There will be a clinical check, EKG findings and laboratory findings. The risk factors will be determined: glucose in blood, lipidogram, nourishment habits, smoking and the therapy during the last year. The periodontological parameters will be measured: probing depth in millimeters for each tooth at least on four places; PBI (Papilla Bleeding Index to determine bleeding and gingival status); recession of gingiva in millimeters from Dentistry vestibular and oral side of each tooth. On the basis of lists parameters the loss of attachment for each tooth will be measured. The degree of inflammatory hyperplasion will be determined with the patients who have been treated with antihypertension medication from nifedipine group Microbiological flora of periodontal pocket will be determined by PCR. The five basic periodontopathogenes will be determined by microDent© kit for each patient. Epidemiological studies on the appearance of dental abnormalities will be carried out on 2000 orthopantograms of patients from Zagreb. The incidence of hypodontia, hyperdontia, invagination, impaction of talon cusp, and cone shape of lateral incisors. Measurements will be carried out on 200 orthopantomograms of Croatian patients aged between 12 and 17 by Lind method (1972). The difference between middle value of Kr/Ko proportion for contra lateral and antagonist teeth will be studied for the entire sample and also for male and female patients respectively. The sample in cephalometric X-ray analysis consists of 300 latero-lateral roentgenograms of patients from Zagreb. They will be grouped according to sex, age and abnormalities of Class II/1, Class II/2, skeletal open bite and abnormalities of progenic complex. The same roentgenograms will be analysed manually and digitally. On the basis of study results the normative of roentgencephalometric variables for mixed and permanent detention will be set as well as for certain orthodontic abnormalities. The sample of photometric analysis will consist of patients aged 25-28 without the orthodontic abnormality, proportioned profile and competent lip. They will be photographed by digital camera. The photos will be calibrated and upon that 14 points on the face, 39 variables, out of which 27 linear and 12 angular, will be marked. Fifty patients aged 12 to 18 will be chosen to investigate the changes in oral cavity flora, salivation changes as well as changes in the chemical structure of saliva with patients having fixed appliances. All of them will use the ordinary tooth paste during therapy and there will be no additional fluoridation. The saliva samples will be taken from patients before the start of orthodontic therapy and after one, two, three, six, nine and twelve months after the start as well as three months after the start of retention. Every sample will be tested for the following parameters: salivary flow, pH, quantity of Str.mutans, quantity of lactobacilli. To establish the biological bond of metal and tissue the metal ion concentration in the oral cavity mucous membrane will be measured and biocompatibility of orthodontic appliances will be determined as well as the possibility of DNA buccal mucous membrane impairment. The cytological smear of buccal mucous membrane will be taken with a cytological brush after the water irrigation to remove dead epithelial cells. Geometric and material nonlinearities will be taken into account, differing from research performed so far. The focus will be on the physically realistic modeling of dentin and periodontal ligament as a result of their importance in dental applications. Periodontal ligament will be modeled by viscoelastic Ogden’s model, with necessary parameters obtained from experimental values. Dentin, consisting of tubule within peritubular part (PTD), and enclosed by intertubular part (ITD) will be modeled by applying continuum micromechanics approach, employing Mori-Tanaka principle and defining Eshelby’s tensor. The ideas of micromechanical dentin formulation by Qin and Swain will be followed. The model enables determination of dentin mechanical properties by taking into account different volume fractions of collagen, mineral phase and fluid (liquid or gas) in particular constituents, PTD and ITD. By knowing mechanical properties and volume fractions of collagen and mineral, by averaging maximum and minimum values obtained by employing Voight and Reuss models, elasticity and shear module of solid phase at PTD and ITD will be determined. The implementation of material model into ABAQUS/Standard–Explicit finite element program will be simplified as Eshelby’s tensor has already being numerically integrated and implemented into UMAT subroutine, developed for computation of composite properties. Institution/University Name of Institution/University School of Dental Medicine, University of Zagreb Number of Employees 250 Number of Researchers 150 Country Croatia Postal Adress Gunduliceva 5 10000 Zagreb Dentistry Research Team Research Team Name Department of Oral Medicine School of Dental Medicine University of Zagreb and coworkers Individual Researcher No Research Team Leader Name DDS, MSc, PhD, Full professor Ana Cekic-Arambasin Research Team Members Team Member 0 PhD, Full professor Josip Lukac [[email protected]] Team Member 1 MD Andjelko Vidovic [[email protected]] Team Member 2 DMD, MSc, PhD Vanja Vucicevic Boras [[email protected]] Team Member 3 DMD, MSc Danica Vidovic Juras [[email protected]] Team Member 4 DMD, MSc Vlaho Brailo [[email protected]] Team Member 5 DMD, MSc, PhD Ivan Alajbeg [[email protected]] Team Member 6 DMD, MSc, PhD Dolores Biocina-Lukenda [[email protected]] Contact Person Name DDS, MSc, PhD, Full professor Ana Cekic-Arambasin Email [email protected] Function principal investigator Phone 0038514802114 Fax 0038514830819 Website www.sfzg.hr Research Team Objectives Main Fields Dentristry Immunology and Immunohaematology Pathology Oral medicine and pathology Partners/Interests researcher industrial partner. Dentristry Immunology and Immunohaematology Pathology 1. Interest in ideas for this research project. 2. Experience with clinical and/or laboratory research methods. AND/OR 3. Experience in the field of oral medicine and pathology SALIVA AS A DIAGNOSTIC FLUID/Saliva is important element of oral and the entire organism health. The role of many salivary constituents is still unclear and their diagnostic and prognostic potential in oral and systemic diseases is unknown. Today's technology provides potential for salivary diagnostics which is equal to the one of the blood. Saliva as a diagnostic fluid has many advantages in comparison with blood which makes it a diagnostic fluid of the future. AIMS: To establish potential of saliva in understanding, diagnosing, monitoring and therapeutic evaluation of oral diseases. HYPOTHESIS: Saliva is susceptible to physiological and/or pathological alterations which are influenced by aging and disease. It is assumable that diseases, particularly ones with oral manifestations cause characteristic alterations in salivary flow and/or composition. Therefore, saliva could be used for explaining so far unknown pathogenic mechanisms of oral diseases, for diagnostic purposes, for follow up and therapeutic evaluation. EXPECTED RESULTS: To establish reference ranges in healthy population of all salivary parameters which will be investigated in this project as markers of the diseases with oral manifestations; to investigate significance of cytokines and oncogenes in pathogenesis and malignant transformation of oral precancerous lesions; to establish salivary markers for the follow up of periodontal disease; to confirm altered levels of salivary and/or serum neuropeptides in BMS patients; to confirm elevated levels of salivary á-amylase as sign of physiological stress in the etiology of RAU and OLP; to evaluate effect and safety of intraoral electrostimulator of salivary secretion; to investigate therapeutic effect of low level laser in the treatment of xerostomia. VALIDATION OF THE RESULTS will be possible because all research protocols and methods will be clearly defined and published and therefore reproducible. SIGNIFICANCE: Completion of the catalogue of salivary constituents. First determination of salivary cell composition and leukocyte subpopulations by flow cytometry. Introducing new protocols for the follow up of oral Dentistry premalignant lesions and early diagnosis of oral cancer. Obtaining objective markers for clinical course and therapeutic response of periodontal disease. Establishing whether BMS is local and/or systemic neuropathy. Defining the role of stress in the etiology of LRP and RAU. Introduction of new therapeutic options for the treatment of xerostomia. Institution/University Name of Institution/University University of Zagreb Number of Employees n.a. Number of Researchers n.a. Country Croatia Postal Adress Gunduliceva 5 10000 Zagreb Dentistry Research Team Research Team Name Ivone Uhac's research team Individual Researcher No Research Team Leader Name DDS, PhD Ivone Uhac Research Team Members Team Member 0 DDS Vedrana Reljic [[email protected]] Team Member 1 DDS Suncana Simonic-Kocijan [[email protected]] Team Member 2 DDS, MS Miranda Muhvic-Urek [[email protected]] Team Member 3 DDS, PhD Ivone Uhac [[email protected]] Team Member 4 DDS, PhD Marica Simunovic-Soskic [[email protected]] Research Team Projects Project Name Posttraumatic stress disorder and the function of stomatognathic system Project Leader DDS PhD Ivone Uhac [[email protected]] Project Funding Agency MINISTRY OF SCIENCE OF REPUBLIC OF CROATIA Project Budget 30000 € Project Start Date 2002-08-20 Project End Date 2006-05-31 Project Partners CROATIA/UNIVERSITY OF RIJEKA/DEPARTMENT OF PROSTHODONTICS Project Summary In our previous investigations it has been reported that TMD are highly present in persons who were exposed to war stress (Periniæ R, Uhaè I. Poredbena rasèlamba simptoma TMD-a rijeèke populacije i prognanika na istom podruèju. Acta stomatol croat 1998;32(suppl.):166; Uhaè et al. The influence of war stress on signs and simptoms of temporomandibular disorders. J Oral Rehabil–in print). On the basis of those results appears a need for more detailed investigations of temporomandibular disorders (TMD) and orofacial pain. The aim of this investigation is to establish the relation between posttraumatic stress disoder (PTSD) and dysfunctions. The main hypothesis is that in PTSD prerequisites for the appearance of dysfunction and orofacial pain exist. Because of the disregulation of catecholamine and serotonin (Southwick 1999), and because the increaded muscle tone (Carlson 1997), we expect primary muscle disorders. Temporomandibular joints will be secondary included. We expect high presence of orofacial pain because of the disregulation of serotonin (Spivak 1999) and frequently comorbidity of PTSD and chronic pain (Sharp 2001).All the participants will be subjected to anamnestical and clinical examination, instrumental, kinesiographic and electromyographic registration and to the pain objectivisation, using methods whose reliability has been previously reported (Helkimo 1974; Fricton 1986; Tsolka 1995; Farella 2000). The exameenes with PTSD with established dysfunction of the stomatognathic system will be classified according to the diagnostic classification of the American Academy of Orofacial Pain. They will be assembled in four groups and submitted to different therapy for a 6 mounth period (EMG-biofeedback, stabilisation intraoral apliances, the combination of two mtehods, and the fourth group without therapy). Efficiency evaluation of each therapy treatment will be conducted using clinical reexaminatiom, electromyographic and kinesiographic registration. According to the obteined results we will be able to extend the pathophisiologic comprehensions of TMD and orofacial pain. The evaluation of each therapy will sugges a model of simply and cheep prevention and noninvasive conservative therapy of groups that are under incrised risk of TMD. Project Website www.medri.hr Project Name Postraumaticstressdisorder and the function of stomatognathic system Project Leader DDS PhD Ivone Uhac [[email protected]] Project Funding Agency MINISTRY OF SCIENCE OF CROATIA Project Budget 30000 € Project Start Date 2002-08-20 Project End Date 2006-05-31 Dentistry Project Partners CROATIA/UNIVERSITY OF RIJEKA/DEPARTMENT OF PROSTHODONTICS Project Summary In our previous investigations it has been reported that TMD are highly present in persons who were exposed to war stress (Periniæ R, Uhaè I. Poredbena rasèlamba simptoma TMD-a rijeèke populacije i prognanika na istom podruèju. Acta stomatol croat 1998;32(suppl.):166; Uhaè et al. The influence of war stress on signs and simptoms of temporomandibular disorders. J Oral Rehabil–in print). On the basis of those results appears a need for more detailed investigations of temporomandibular disorders (TMD) and orofacial pain. The aim of this investigation is to establish the relation between posttraumatic stress disoder (PTSD) and dysfunctions. The main hypothesis is that in PTSD prerequisites for the appearance of dysfunction and orofacial pain exist. Because of the disregulation of catecholamine and serotonin (Southwick 1999), and because the increaded muscle tone (Carlson 1997), we expect primary muscle disorders. Temporomandibular joints will be secondary included. We expect high presence of orofacial pain because of the disregulation of serotonin (Spivak 1999) and frequently comorbidity of PTSD and chronic pain (Sharp 2001).All the participants will be subjected to anamnestical and clinical examination, instrumental, kinesiographic and electromyographic registration and to the pain objectivisation, using methods whose reliability has been previously reported (Helkimo 1974; Fricton 1986; Tsolka 1995; Farella 2000). The exameenes with PTSD with established dysfunction of the stomatognathic system will be classified according to the diagnostic classification of the American Academy of Orofacial Pain. They will be assembled in four groups and submitted to different therapy for a 6 mounth period (EMG-biofeedback, stabilisation intraoral apliances, the combination of two mtehods, and the fourth group without therapy). Efficiency evaluation of each therapy treatment will be conducted using clinical reexaminatiom, electromyographic and kinesiographic registration. According to the obteined results we will be able to extend the pathophisiologic comprehensions of TMD and orofacial pain. The evaluation of each therapy will sugges a model of simply and cheep prevention and noninvasive conservative therapy of groups that are under incrised risk of TMD. Project Website www.medri.hr Contact Person Name DDS, PhD Ivone Uhac Email [email protected] Function Head of Department of Prosthodontics Phone 0038551345633 Fax 0038551345630 Website medri.hr Research Team Objectives Main Fields Dentristry Psychiatry Orofacial pain is one of the most common forms of the regional pain. In its acute form it is associated to tooth or periodontal tissue. The chronic form is mainly associated with temporomandibular disorder and atypical facial pain. The etiology and pathogenesis of the chronic forms are not fully understood and to present time uniform therapy does not exist. The hypothesis exists that this conditions are multicausal and are connected with trauma, stress, parafunctions and systemic disorders that play a significant roll in their onset. The results of the numerous clinical studies that examined the influence of various factors on the onset of orofacial pain are not conclusive. In order to assess the influence of occlusal factors, stress and trauma on orofacial pain we will use animal model to induce and assess the orofacial pain by one or a combination of etiological causes. The project is divided into two parts: First part as a clinical research and second as experimental on the animal model. Our hypothesis is that by gathering more information and knowledge of this conditions a new need for specialists and interdisciplinary approach will arise together with the need for increased preventive measures and regular controls. We expect to find that the experimental part will reveal or suggest exact data of the influence of acute and chronic stress, pathological response to stress (PTSD), and bruxism on orofacial pain and show the effectiveness of corticosteroids in treatment of orofacial pain. Partners/Interests researcher industrial partner Dentristry Psychiatry Pharmacology Dentistry same scientific interests - examine the influence of the systemic diseases on function of stomatognatic system - examine the influence of the acute stress on orofacial pain, i.e. on masticatory muscles and TMJ pain - examine the influence of the chronic stress on orofacial pain, i.e. on masticatory muscles and TMJ pain examine the influence of pathological response to stress on orofacial pain, i.e. on masticatory muscles and TMJ pain - examine the influence of microtrauma-bruxism on orofacial pain, i.e. on masticatory muscles and TMJ pain - examine of the combined influence of multiple factors on orofacial pain, i.e. on masticatory muscles and TMJ pain Institution/University Name of Institution/University Faculty of Medicine - School of Dentistry Number of Employees 350 Number of Researchers 100 Country Croatia Postal Adress Brace Branchetta 20 51000 Rijeka Dentistry Research Team Research Team Name prosthodontic team Individual Researcher No Research Team Leader Name PhD;MSc;Prof. Melita Valentic-Peruzovic Research Team Members Team Member 0 prof Mario Cifrek [[email protected]] Team Member 1 PhD Amir Catic [[email protected]] Team Member 2 prof. Adnan Catovic [[email protected]] Team Member 3 assistant Ivica Pelivan [[email protected]] Team Member 4 MSc Davor Illes [[email protected]] Team Member 5 PhD Iva Alajbeg [[email protected]] Research Team Projects Project Name Analysis of function and form of stomatognathic system Project Leader prof. Melita Valentic-Peruzovic [[email protected]] Project Funding Agency Ministery of science and sport Project Budget 15000 € Project Start Date 2003-10-01 Project End Date 2006-06-30 Project Partners Croatia, School of Dental Medicine, University of Zagreb,Prosthetic Dentistry Project Summary electromyography (EMG), gnathology, temporomandibular dysfunction (TMD), Whiplash trauma, optoelectronic system, echo-acoustics system for the threedimensional localisation, articulators, bitting appliances, VAS scale, teledentistry Project Website www.mzt.hr Project Name Gnathology at net, Virtual textbook Project Leader prof. Melita Valentic-Peruzovic [[email protected]] Project Funding Agency Ministery of science and sport Project Budget 5000 € Project Start Date 2001-10-01 Project End Date 2002-10-01 Project Partners Croatia, School of Dental Medicine, University of Zagreb Project Summary Virtual textbook of Gnathology for interactive learning and student on-line seminars Project Website http://gnato.sfzg.hr/ Contact Person Name PhD;MSc;Prof. Melita Valentic-Peruzovic Email [email protected] Function University Professor at the School of Dental Medicine Phone 00385 1 4802 150 Fax 0038514802159 Website sfzg.hr Research Team Objectives Main Fields Dentristry Information Technology, Statistics, Documentation Public health services The investigation will enable the application of new classification systems for complete and partial edentulism in epidemiological and clinical investigations in Croatian population as well as the Dentistry comparison with international results. Model development for multidisciplinary data connection will enable the referring of patients to proper diagnostic procedures. Experimental results, as well as standardization of electromyographic registrations and acoustic analysis of occlusal sounds and TMJ together with complete functional analysis and three dimensional kinematic model of masticatory system, match with newest international results on masticatory system biomechanics. Cognitions in the field of reflexology (especially emg silent period recording) are of the great interest in many international investigation projects on craniomandibular research. Prosthodontic treatments, especially when related to dental implants therapy, demand detailed analysis of all available biological factors for the purpose of harmonic integration in functional unit. Facial 2D and 3D analysis using modern digital techniques as well as its comparison with masticatory system function, match thematically and methodologically with international scientific results. Partners/Interests researcher Dentristry Public health services Information Technology, Statistics, Documentation biodynamic research in dentistry Emg or axyiographic research teledentistry Biodynamics of masticatory system and restorative procedures in dentistry- will be investigated by using different methods such as: electromyography, gnathosonography, gnathodinamometry, 3Daccelerometry; -implementation of non-invasive objective methods for temporomandibular dysfunction (TMD) diagnosis and also - the investigation of effects of different prosthodontic restorations on masticatory system function and dysfunction - Changes in biodynamics and influences of ageing process on prosthodontic restorations, neuromuscular adaptation and masticatory efficiency will be investigated. This investigation will enable the implementation of the most contemporary technological achievements in the field of prosthodontics by way of enabling the postulates for proper checking of patient’s functional status. The consequences caused by unrecognised organic or psychological patient’s condition have to be prevented on time. The aim is also to introduce specific protocols for multidisciplinary clinical cases and provide communication and date transferring between different clinical centres. This will enable multidisciplinary analysis and distant data transfer – teledentistry. Our aim is also to provide diagnostic and technological support for establishing an expert centre for Croatia and, to enable cooperation with European and international expert teams during the project work. Institution/University Name of Institution/University University of Zagreb, School of Dental Medicine Number of Employees 120 Number of Researchers 90 Country Croatia Postal Adress Gunduluceva 5 10000 Zagreb Dentistry Research Team Research Team Name department for prosthetic dentistry, unit for temporomandibular disorder and orofacial pain Individual Researcher No Research Team Leader Name DDS, PhD Renata Grzic Research Team Members Team Member 0 DDS, MD Vesna Fugosic [[email protected]] Team Member 1 DDS, MS Vlatka Mikic [[email protected]] Team Member 0 MD, PhD Aleksandar Smokvina [[email protected]] Team Member 1 DDS, PhD Daniela Kovacevic Pavicic [[email protected]] Team Member 0 MD, PhD Tanja Franciskovic [[email protected]] Team Member 1 DDS, MS Robert Antonic [[email protected]] Team Member 0 DDS, MS Danko Bakarcic [[email protected]] Team Member 1 MD, MS Jasna Gobic [[email protected]] Team Member 0 DDS, PhD Renata Grzic [[email protected]] Team Member 1 Phd, DMD Daniela Kovacevic Pavicic [[email protected]] Team Member 0 MSc, DMD Vlatka Mikic [[email protected]] Team Member 1 MSc, DMD Danko Bakarcic [[email protected]] Team Member 0 DMD, MD Vesna Fugosic [[email protected]] Team Member 1 Phd, DMD Zdravko Delic [[email protected]] Contact Person Name DMD, PhD Renata Grzic Email [email protected] Function VICE DEAN, UNIVERSITY OF MEDICINE, DENTAL STUDIES, RIJEKA Phone 00385 51 345631 Fax 00385 51 345630 Website www.medri.hr Research Team Objectives Main Fields Dentristry Radiology Internal Medicine Prosthodontics, Gnathology, Internal Medicine, Nuclear Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology Partners/Interests researcher Dentristry Radiology Internal Medicine Have interest in this field, Have done some other research on similar or other projects connected to this theme Sex hormones, depending on reproductive age of the women, have an influence on the human body, including stomatognathic system as well. They are one of the factors responsible for maintainance of health in stomatognathic system; modify existence of chronic pain in the orofacial region, bone mineral density of viscerocranium, state of oral mucosa and psychological status. Absence of female sex hormones in menopause can lead to calcium homeostasis disorder, and can cause osteopenia, even osteoporosis. Although so, in women with dentolous jaws and appropriate masticatory function the bone loss in mandibula and maxilla is inhibited. In TMD cortisone disbalance caused by stress and with co-existing psychological disorders, mostly depression, often cause muscle disorders. Thyroid gland hormones regulate basal metabolism and calcium ion levels in bones and blood. The aim is to analyze hormonal status of TSH, T4, estradiol and cortisone in women in different phases of reproductive age and connect them to symptoms in TMD. The aim is to observe longitudinally bone mineral density in women with natural dentition and different prosthetic appliances, comparing them Dentistry to sex hormone levels, hormonal status and bone density in bruxism (increased masticatory forces), and psychological status on oral health. We expect to determine connection of hormonal and psychological status on changes in stomatognathic system and explain it better. The role of hormonal disbalance, emotional and social status and psychological profile compared to symptoms in TMD, reduction in bone density, changes on oral mucosa and patient's attitude towards dental and prosthetic health will be also better explained. RIA and IRMA Count-A-Count method will analyze hormonal status. STAI and Beck depression and anxiety tests will evaluate psychological status. SCL 90, EPQ i PIE personality questionaries will analyze psychological symptoms. MANSA questionary will test the quality of life. X-ray images will be digitalized. Microdensitometry method will analyze bone mineral density. RDC/TMD questionary will evaluate signs and symptoms in TMD. The results are expected to show influence of hormones in primary and secondary disorders, loss of bone structures in jaws and psychological attitude, comparing them to health of the stomatognathic system. Etiology of TMD will be better explained and therapeutic procedures will be improved. Institution/University Name of Institution/University University of Medicine, Dental Studies- Rijeka Number of Employees 350 Number of Researchers 100 Country Croatia Postal Adress Kresimirova 40 51000 Rijeka Dentistry Research Team Research Team Name Endodontics Individual Researcher No Research Team Leader Name Prof. Dr. Peter Städtler Contact Person Name Prof. Dr. Peter Städtler Email [email protected] Function Phone +43 316 3853440 Fax Website http://www.meduni-graz.at Research Team Objectives Main Fields Dentistry Partners/Interests Dentistry Institution/University Name of Institution/University University Clinics for Dentistry, Medical University Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 12 8036 Graz Dermatology Research Team Research Team Name Teledermatology Individual Researcher No Research Team Leader Name H. Peter Soyer, MD Contact Person Name H. Peter Soyer, MD Email [email protected] Function Phone +43-316-385-80310 Fax +43-316-385-4957 Website http://www.meduni-graz.at Research Team Objectives Main Fields Dermatology Venereology Partners/Interests Dermatology Venereology Austrian tourists with skin diseases can get medical advice from University Departments of Dermatology in Austria using a standard webbrowser and conventional digital camera or cellular phones. In addition, a bilateral collaboration with Croatian dermatologists will facilitate the management based on individual needs. In order to get a broad distribution for Austrian citizens using this service a collaboration with netdoktor.at will be established. Institution/University Name of Institution/University Department of Dermatology, Medical University Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 8 8036 Graz Epidemiology Research Team Research Team Name Institute of Oncology "Prof. Dr. Al. Trestioreanu" Bucharest Individual Researcher No Research Team Leader Name Mathematician Adela Ratiu Contact Person Name Mathematician Adela Ratiu Email [email protected] Function Head, Department of Medical Statistics Phone +40-21-6875542, +40-788-625933 Fax +40-21-318 3262 Website www.iob.ro Research Team Objectives Main Fields Epidemiology Information Technology, Statistics, Documentation - cancer registries (hospital-based and population-based) - cancer statistics - cancer databases Partners/Interests researcher Epidemiology experience in hospital activities - methods of quality control evaluation in medical reports Institution/University Name of Institution/University Institute of Oncology "Prof. Dr. Al. Trestioreanu" Bucharest Number of Employees 640 Number of Researchers 50 Country Romania Postal Adress Fundeni Road, 022328 252 02232 Bucharest Epidemiology Research Team Research Team Name Belgrade MS Epidemiology Group Individual Researcher No Research Team Leader Name MD, PhD. Tatjana Pekmezovic Research Team Members Team Member 0 MD Jelena Kostic [[email protected]] Team Member 1 MD Nebojsa Stojsavljevic [[email protected]] Team Member 2 MD, MSc. Darija Kisic [[email protected]] Team Member 3 MD, M.Sc Irena Dujmovic [[email protected]] Team Member 4 MD, M.Sc. Sarlota Mesaros [[email protected]] Team Member 5 MD, PhD. Mirjana Jarebinski [[email protected]] Team Member 6 MD, PhD. Jelena Drulovic [[email protected]] Research Team Projects Project Name QUALITY OF LIFE IN NEUROLOGICAL DISORDERS: GLOBAL MEASUREMENT OF EFFECTS OF DISEASES Project Leader MD, PhD Tatjana Pekmezovic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary The health-related quality of life (HRQL) measures are alternative indicators of the impact of the disease. In this project studies will be performed to examine: 1) HRQL of selected neurological patients in order to provide a global measure of disease impact, 2) HRQL as an outcome measure in treatment interventions, 3) HRQL as prognostic factor and 4) validity of disease-specific HRQL questionnaires. Additional aims of the project are assessment of the cost of neurological disorders and analysis of the influence of disease severity and HRQL on the cost, respectively. Those studies will be conducted in population-based cohorts and hospital-based samples. The expected outcomes of the project comprise: 1) definition of the determinants of the HRQL in patients with selected neurological disorders (multiple sclerosis, myasthenia gravis, neurosarcoidosis, and others) in our population, 2) evaluated of the effects of various forms of treatments and interventions on HRQL in our patients, 3) assessment of the potential role of HRQL as a prognostic factor for the progression of certain neurological diseases, 4) existence of validated disease-specific HRQL questionnaires according to specificities of Serbian language and cultural settlements, 5) estimated incidence and prevalence of selected neurological disorders in different regions of Serbia, 6) evaluated cost of selected neurological disorders in Serbia. Project Website www.mntr.sr.gov.yu Contact Person Name MD, PhD. Tatjana Pekmezovic Email [email protected] Function Associate Professor of Epidemiology, School of Medicine Phone +381 11 3615768 Fax +381 11 3615768 Website med.bg.ac.yu Research Team Objectives Main Fields Epidemiology Neurology Public health services Our main research fields include different aspects of epidemiology of Multiple Sclerosis (MS)such as: measurement of MS prevalence and incidence in Belgrade (population-based MS Registry established Epidemiology in 1996), life quality studies including assessment of treatment efficiency, studies of estimation of global impact of the disease on the individual as well as estimation of MS cost. Partners/Interests researcher Epidemiology Neurology Public health services -Research experience in both life quality studies and cost evaluation studies in home countries -To define the determinants (physical, social, emotional, and others) of the health-related quality of life (HRQL) among patients with selected neurological disorders (multiple sclerosis, myasthenia gravis, neurosarcoidosis, some others) -To evaluate the effects of various treatments and interventions (immunomodulating drugs, antidepressants, surgery, physical therapy and rehabilitation) on HRQL. -To establish the potential prognostic factors for progression of the diseases associated with HRQL. -To estimate cost of selected neurological disorders with special emphasis on direct and indirect costs of multiple sclerosis as: 1) one of the most common causes of chronic disability among young adults and 2) extremely costly disease. -To incorporate HRQL instruments into the care process. Institution/University Name of Institution/University School of Medicine, University of Belgrade Number of Employees 1172 Number of Researchers 872 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Epidemiology Research Team Research Team Name Croatian Adult Health Survey 2003 - Cardiovascular Health Individual Researcher No Research Team Leader Name Professor Emeritus Silvije Vuletic Research Team Members Team Member 0 Assistant Ivana Kolcic [[email protected]] Team Member 1 Assistant Ozren Polasek [[email protected]] Team Member 2 Assistant Ognjen Brborovic [[email protected]] Team Member 3 Assistant Aleksandar Dzakula [[email protected]] Team Member 4 Assistant Ranko Stevanovic [[email protected]] Team Member 5 Professor Marija Strnad [[email protected]] Team Member 6 Assistant Sanja Music Milanovic [[email protected]] Team Member 7 Professor Davor Ivankovic [[email protected]] Team Member 8 Professor Josipa Kern [[email protected]] Research Team Projects Project Name 2003 Croatian Adulat Health Survey Project Leader Professor Emeritus Silvije Vuletic [[email protected]] Project Funding Agency WB IBRD-a 4513-0 HR Project Budget 72000 € Project Start Date 2002-11-01 Project End Date 2004-12-31 Project Partners Canadian Agency for International Health Project Summary Project. The Health Systems Project targeted the prevention of cardiovascular disease in Croatia. One important component of the Project is a survey of adults that provides a comprehensive assessment of the health of Croatians, including their access to and use of health care services, health status, and determinants of health such as smoking, physical activity, nutrition and alcohol use. The 2001 Croatian Census of Population was used to select a representative sample of households to be included in this survey. Survey results are representative for six officially defined regions of Croatia. The survey questionnaire was designed through consultation with many experts from epidemiologists and public health, drawing on known survey instruments. First results were published in: Béland Y, Bailie L, and Page J. Statistics Canada, Croatian Ministry of Health and Central Bureau of Statistics: a joint effort in implementing the 2003 Croatian Adult Health Survey, 2004 Proceedings of the American Statistical Association Meeting, Survey Research Methods. Toronto, Canada: American Statistical Association, 2004.; Kern J, Strnad M, Coric T, Vuletic S. Cardiovascular risk factors in Croatia: struggling to provide the evidence for developing policy recommendations. BMJ. 2005 Jul 23;331(7510):208-10. Project Website Contact Person Name Professor Emeritus Silvije Vuletic Email [email protected] Function Adviser Consultant Phone +38514590100 Fax +38514684441 Website www.snz.hr Research Team Objectives Main Fields Epidemiology Public health services Social medicine Project. The Health Systems Project targeted the prevention of cardiovascular disease in Croatia. One Epidemiology important component of the Project is a survey of adults that provides a comprehensive assessment of the health of Croatians, including their access to and use of health care services, health status, and determinants of health such as smoking, physical activity, nutrition and alcohol use. The 2001 Croatian Census of Population was used to select a representative sample of households to be included in this survey. Survey results are representative for six officially defined regions of Croatia. The survey questionnaire was designed through consultation with many experts from epidemiologists and public health, drawing on known survey instruments. First results were published in BMJ (Kern J, Strnad M, Coric T, Vuletic S. Cardiovascular risk factors in Croatia: struggling to provide the evidence for developing policy recommendations. BMJ. 2005 Jul 23;331(7510):208-10.) Partners/Interests researcher Epidemiology Public health services Social medicine Researcher working on similar problems in other European countries Regionalism of Cardiovascular Bihevioural Risk Factors The main goals of this research are to investigate: (1) the occurrence of cardiovascular risks clusters and their regional distribution within Croatia, (2) evolution of such clusters in individuals and their emergence on a population level, (3) recognition of public health professionals behaviour concerning the cardiovascular health promotion, (4) population changes of cardiovascular risk factors and mortality during the five year period, (5) to develop a new national public health intervention model (NPHI model) based on regional peculiarities and needs relating to the cardiovascular cluster structure. The purpose of the research is to reduce prevalence of cardiovascular risk factors in the Croatian population, and, consequently, decrease in the cardiovascular morbidity and mortality on a population level. The final goal of the project is to develop regionally specific models of intervention that will be implemented by county public health institutes, with a final goal of reducing cardiovascular burden of disease. Continuation of Croatian Adult Health Survey every five years should be the basis for development of national public health information system for surveillance of CVD in Croatia. This model could also be applied in other countries, experiencing similar problems. Institution/University Name of Institution/University University of Zagreb, School of Medicine, A.S. School of PH Number of Employees 700 Number of Researchers 400 Country Croatia Postal Adress Rockefellerova 4 10000 Zagreb Epidemiology Research Team Research Team Name Epidemiological study in myelodysplastic syndrome Individual Researcher No Research Team Leader Name Dr. Radu Gologan Contact Person Name Dr., MD, PhD Radu Gologan Email [email protected] Function Center of Excellence of the International Foundation for MDS Phone +40 21 240 2020 Fax +40 21 240 8843 Website http://www.mds-foundation.org/mds-centers-excellence.htm Research Team Objectives Main Fields Epidemiology hematology myelodysplastic syndrome Partners/Interests researcher Epidemiology Objectives: The extending the registry of the patients with myelodysplastic syndrome existing already at the Clinic of Hematology, Fundeni Clinical Institute at the national level. Expected results: A better knowledge of the incidence of the myelodysplastic syndrome in Romania, the relevance of the possible its regional variations and a better evaluations of the costs of treatments of these patients. Impact: To report the data to the Romanian and European leading forums. An improvement of the measures of preventing and treatment of the patients with myelodysplastic syndrome. Contribution to the EU or regional policy: There is an increasing interest in Europe for the completing of the national registries of the patients with different diseases. In the field of hematology, there are few European patients registries concerning the myelodysplastic syndrome EU research: In the field of the Myelodysplastic Syndrome there are powerful centers of care and research in Europe. An European organization, namely already exists aiming to support the cooperation between national and regional centers. European research potential: To compare the data obtained with those from other European countries and to present them in the frame of Leukemia Net. Institution/University Name of Institution/University Clinic of Hematology, Fundeni Clinical Institute Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Sos. Fundeni 258 50096 Bucharest Epidemiology Research Team Research Team Name School of Medicine Belgrade Individual Researcher No Research Team Leader Name Prof. Dr. Slavenka Jankovic Research Team Members Team Member 0 Prof. Ivana Novakovic [[email protected]] Team Member 1 Prof. Jelena Marinkovic [[email protected]] Team Member 2 MD, PhD Danica Bukvic [[email protected]] Team Member 3 Ass. Dr. Natasa Maksimovic [[email protected]] Team Member 4 Molecular biologist Nela Maksimovic [[email protected]] Team Member 5 Ass. Dr. Momcilo Ristanovic [[email protected]] Team Member 6 Prof. Dr. Ljubica Djukanovic [[email protected]] Research Team Projects Project Name Clinical/epidemiological investigations concerning diseases of medical and public health importance Project Leader Prof. Dr. Slavenka Jankovic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners We search for partners who have an expertise in clinical and fild investigations of BEN, and who have excellence and opportunity in pathomorphological analysis. Project Summary Balkan endemic nephropathy (BEN) is chronic tubulointerstitial disease of unknown etiology despite to the numerous studies devoted to investigations of BEN etiology. It was hypothesized that both genetic and environmental factors are involved in the development of BEN. Pathohystological studies showed that morphological changes in BEN are non-specific and in the chronic phase they are quite similar to changes in other chronic interstitial diseases. Several authors described changes on kidneys arterioles in the early stage of the disease and pointed out to the similarity of BEN and cyclosporin (CsA) induced nephropathy: multifocal microvascular hyalinosis (cyclosporin arteriolopathy) and areas of band-like hypocellular interstitial sclerosis with tubular atrophy. Recently, numerous in vitro and in vivo studies indicated that several fibrogenic cytokines are implicated in the pathogenesis of CsA nephropathy. Futhermore, it was shown that CsA-induced fibrosis could be independent of renal hemodynamics and mediated, at least partly, through angiotensin II (Ang II) induction of TGF-beta1 expression. So, Ang II, that is well known factor implicated in fibrosis, could contribute to fibrosis in CsA nephropathy by inducing TGF-beta1. Morphological findings in BEN nephropathy indicated that renin-angiotensin-aldosterone system (RAAS) and fibrogenic cytokines might be implicated in the pathogenessi of the disease. Therefore, the aim of our investigation will be to examine the involvement of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), Ang II type 1 receptor (AT1R) and TGF beta gene polymorphisms in predisposition and progression of BEN. Since the mid 1990s, many studies have been devoted to RAAS gene polymorphisms as factors that predispose to multifactorial renal diseases. The results reported are controversial but several author groups showed that polymorphism of the ACE gene was associated with renal disease progression. The investigation (study) will be carried out in collaboration of Institute of Epidemiology and Institute of Biology and Human Genetics, School of Medicine, University of Belgrade, and Institute of Endemic Nephropathy, Lazarevac. The coworkers had great experience in field and clinical investigations of patients with BEN (prof Ljubica Djukanovic, scientific researcher Dr. Danica Bukvic, Prof. Dr. Slavenka Jankovic), and in genetic analysis (ass. prof. Dr. Ivana Novakovic, Ass. Dr. Momcilo Ristanovic, molecular biologist Nela Maksimovic). The study will involve the patients with BEN, diagnosed according to criteria proposed by Danilovic and selected in systematic investigation of inhabitants in BEN affected village in the Kolubara region and two controls groups – one consisted of patients with kidney diseases other than BEN and the other consisted of healthy persons. Detailed clinical, ultrasound and biochemical investigations of patients will enable to analyze relevance of genetic risk factors in the context of clinical and biochemical variables. DNA study will start by collection of DNA samples from persons belonging both BEN and control groups. Analysis of selected polymorphisms of ACE, AGT, AT1R and Epidemiology TGF beta genes will be based on simple PCR method for deletion/insertion polymorphism, and PCR/RFLPS method or PCR/ARMS method for single nucleotide polymorphisms (SNPs). Detected allele frequencies and genotypes will be compared within groups and possible association of gene polymorphisms with other clinical, ultrasound and biochemical parameters in BEN will be studied. The studies directed to examination of the role of the RAAS in the expression of TGF-beta1 and other fibrogenic cytokine as well as matrix proteins in renal tissue of patients with the early phase of BEN would be reasonable. Project Website Contact Person Name Prof. Dr. Slavenka Jankovic Email [email protected] Function Professor Phone 00381112164794 Fax 00381113615768 Website http://www.med.bg.ac.yu Research Team Objectives Main Fields Epidemiology Internal Medicine Genetics Our main fields include clinical, epidemiological and genetic investigation of Balkan endemic nephropathy Partners/Interests researcher Epidemiology Internal Medicine Genetics We search for experts in clinical and field investigation of BEN and partners that have excellence and opportunity in pathomorphological analysis. Detailed clinical, ultrasound and biochemical investigations of patients with Balkan endemic nephropathy will enable to analyze relevance of genetic risk factors in the context of clinical and biochemical variables. The studies directed to examination of the role of the RAAS in the expression of TGF-beta1 and other fibrogenic cytokine as well as matrix proteins in renal tissue of patients with the early phase of BEN would be reasonable. Institution/University Name of Institution/University Institute of Epidemiology, University of Belgrade Number of Employees 14 Number of Researchers 11 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Epidemiology Research Team Research Team Name Individual Researcher No Research Team Leader Name Dr sci. Jadranka DIZDAREVIĆ Research Team Members Team Member 0 Dr sci. Jadranka DIZDAREVIĆ Team Member 1 Fadila Serdarević MD,MPH Team Member 2 Semir Vranić MD Team Member 3 Jasmin Ćeranić, MD,MBA Team Member 4 Goran Stojkanovic, MD Team Member 5 Mohamed Ardat MD Team Member 6 Olga Gurjeva, MD, PhD Contact Person Name Dr sci. Jadranka DIZDAREVIĆ Email [email protected] Function professor, Department of Gynaecology Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Epidemiology Low Genital Tract Infections, Screening, Preterm Delivery, South Eastern Europe Partners/Interests Is there a need for routine antenatal screening on Low Genital Tract Infections in South Eastern Europe? Prevalence of low genital tract infections (LGTI) in South Eastern Europe is unknown. The combined impact of poverty, a high rate of unemployment, deteriorating economic conditions, decline in provision of basic services, conflicts and migration has resulted in the presence of increased risk in this region. In resource - poor settings, managing of LGTI is challenging in terms of diagnostic accuracy and appropriate treatment. To date no systematic strategies have been developed for this vulnerable population in the area of LGTI awareness and prevention. The proposed investigation will undertake a multi-center multi-stage cluster Primary Health Care (PHC) based cross-sectional survey, including screening for Low Genital Tract Infections biomarkers, in order to asses the relationship between most important risk factors, presence of symptoms, awareness of symptoms and Trichomonas Vaginalis, BV, Chlamidia Trachomatis, Gonorrhea, Candida Albicans among pregnant women in South Eastern Europe, coming for routine gynecological examination between 17-24 gestational week. The aim of this study is to determine the prevalence of lower genital tract infection by analysis of cervico-vaginal secret and the prevalence of symptoms in pregnant women. We want to explore whether the routine screening for the most common LGTI is warranted regard to the costs and potential benefits of screening the asymptomatic LGTI infections that might cause preterm delivery as a main cause of both fetal and maternal morbidity and mortality. Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Genetics Research Team Research Team Name Individual Researcher No Research Team Leader Name DVM, PhD, senior scientist Nela Pivac Research Team Members Team Member 0 BSc Martina Deželjin [[email protected]] Team Member 1 senior scientist Dorotea Muck-Šeler [[email protected]] Team Member 2 BSc Maja Mustapic [[email protected]] Contact Person Name DVM, PhD, senior scientist Nela Pivac Email [email protected] Function senior scientist at Rudjer Boskovic Institute Phone 385 1 4571 207 Fax 385 1 456 1010 Website www.irb.hr Research Team Objectives Main Fields Genetics Pharmacology Psychiatry biological and genetic basis of posttraumatic stress disorder, acute stress reaction, alcoholism, ADHD and suicidal behaviour Partners/Interests researcher Psychiatry Genetics Pharmacology collaboration in the research the research on the psychobiological factors in psychiatric disorders Institution/University Name of Institution/University Rudjer Boskovic Institute Number of Employees 300 Number of Researchers 400 Country Croatia Postal Adress Bijenicka 54 10000 Zagreb Genetics Research Team Research Team Name Endocrine oncology and hereditary tumors Individual Researcher No Research Team Leader Name MD, PhD Svetozar Damjanovic Research Team Members Team Member 0 mol. biologist, Bsci Tatjana Perisic [] Team Member 1 mol. biologist, PhD Jadranka Dundjerski [] Team Member 2 mol. biologist, PhD Gordana Matic [] Team Member 3 mol. biologist, Bsci Katarina Mirkovic [] Team Member 4 mol. biologist, Bsci Jelena Nikolic [] Team Member 5 mol. biologist, Bsci Jovana Vignjevic [] Team Member 6 mol. biologist, Bsci Jadranka Antic [] Team Member 7 MD, Msci Bpjana Beleslin [] Team Member 8 MD, Bsci Ivana Bozic [] Team Member 9 MD, Bsci Tanja Isailovic [] Team Member 10 MD, Bsci Bojana Popovic [] Team Member 11 MD, Msci Sanja Ognjanovic [] Team Member 12 MD, PhD Milan Petakov [] Team Member 13 MD, PhD Djuro Macut [] Team Member 14 mol. biologist, Bsci Ivana Elakovic [] Team Member 15 MD, PhD Ivan Paunovic [] Research Team Projects Project Name Psychobiology of posttraumatic stress disorder Project Leader MD, PhD Eric Vermetten [[email protected]] Project Funding Agency EC, FP6 Project Budget 1300000 € Project Start Date 2004-10-01 Project End Date 2007-10-01 Project Partners Serbia, Institute for Nuclear Sciences, Belgrade University Serbia, International Aid Network, Belgrade Serbia, Institute for Biological Research, Belgrade University, Biochemistry UK, Queen Mary and Westfield College-University of London, Psychiatry Italy, Universita Degli Studi di Bari, Psychiatry Croatia, Meical School of Rijeka, University of Rijeka Project Summary It is likely that increased HPA axis sensitivity can be connected with specific glucocorticoid receptor gene polymorphism. Long term activation of HPA axis in patients with PTSD could be associated with a) impaired or normal cortisol suppression with lower doses of Dexamethasone, b) central obesity, c) hypertension and d) inhibitory effects on secretion of sex steroids and growth hormone. Differential response to low dose of Dexamethasone with hypothetically different pattern of POMC cleavage in health and illness could be of help in making difference between subtypes of PTSD. Visceral obesity, insulin resistance and hypertension are major components of metabolic syndrome. Number of patients with PTSD has the same characteristics and all patients with hypercortisolism (Cushing’s syndrome). Depression, so common in Cushing’s syndrome can be found as a co-morbid state in patients with PTSD. PTSD and metabolic syndrome, therefore, may have in common functional properties of glucocorticoid receptor (GR) due to specific gene BclI polymorphism within the intron upstream of GR exon 2, which is associated with visceral obesity, hypertension, insulin resistance and elevated cortisol levels. Thus, we expect to find specific changes in anthropometric measurements of patients with PTSD and higher incidence of hypertension and obesity. Project Website Genetics Project Name Psychobiology of posttraumatic stress disorder Project Leader MD, PhD Eric Vermetten [[email protected]] Project Funding Agency EC, FP6 Project Budget 1300000 € Project Start Date 2004-10-01 Project End Date 2007-10-01 Project Partners Serbia, Institute for Nuclear Sciences, Belgrade University Serbia, International Aid Network, Belgrade Serbia, Institute for Biological Research, Belgrade University, Biochemistry UK, Queen Mary and Westfield College-University of London, Psychiatry Italy, Universita Degli Studi di Bari, Psychiatry Croatia, Meical School of Rijeka, University of Rijeka Project Summary It is likely that increased HPA axis sensitivity can be connected with specific glucocorticoid receptor gene polymorphism. Long term activation of HPA axis in patients with PTSD could be associated with a) impaired or normal cortisol suppression with lower doses of Dexamethasone, b) central obesity, c) hypertension and d) inhibitory effects on secretion of sex steroids and growth hormone. Differential response to low dose of Dexamethasone with hypothetically different pattern of POMC cleavage in health and illness could be of help in making difference between subtypes of PTSD. Visceral obesity, insulin resistance and hypertension are major components of metabolic syndrome. Number of patients with PTSD has the same characteristics and all patients with hypercortisolism (Cushing’s syndrome). Depression, so common in Cushing’s syndrome can be found as a co-morbid state in patients with PTSD. PTSD and metabolic syndrome, therefore, may have in common functional properties of glucocorticoid receptor (GR) due to specific gene BclI polymorphism within the intron upstream of GR exon 2, which is associated with visceral obesity, hypertension, insulin resistance and elevated cortisol levels. Thus, we expect to find specific changes in anthropometric measurements of patients with PTSD and higher incidence of hypertension and obesity. Project Name Psychobiology of posttraumatic stress disorder Project Leader MD, PhD Eric Vermetten [[email protected]] Project Funding Agency EC, FP6 Project Budget 1300000 € Project Start Date 2004-10-01 Project End Date 2007-10-01 Project Partners Serbia, Institute for Nuclear Sciences, Belgrade University Serbia, International Aid Network, Belgrade Serbia, Institute for Biological Research, Belgrade University, Biochemistry UK, Queen Mary and Westfield College-University of London, Psychiatry Italy, Universita Degli Studi di Bari, Psychiatry Croatia, Meical School of Rijeka, University of Rijeka Project Summary It is likely that increased HPA axis sensitivity can be connected with specific glucocorticoid receptor gene polymorphism. Long term activation of HPA axis in patients with PTSD could be associated with a) impaired or normal cortisol suppression with lower doses of Dexamethasone, b) central obesity, c) hypertension and d) inhibitory effects on secretion of sex steroids and growth hormone. Differential response to low dose of Dexamethasone with hypothetically different pattern of POMC cleavage in health and illness could be of help in making difference between subtypes of PTSD. Visceral obesity, insulin resistance and hypertension are major components of metabolic syndrome. Number of patients with PTSD has the same characteristics and all patients with hypercortisolism (Cushing’s syndrome). Depression, so common in Cushing’s syndrome can be found as a co-morbid state in patients with PTSD. PTSD and metabolic syndrome, therefore, may have in common functional properties of glucocorticoid receptor (GR) due to specific gene BclI polymorphism within the intron upstream of GR exon 2, which is associated with visceral obesity, hypertension, insulin resistance and elevated cortisol levels. Thus, we expect to find specific changes in anthropometric measurements of patients with PTSD and higher incidence of hypertension and obesity. Contact Person Name MD, PhD Svetozar Damjanovic Email [email protected] Genetics Function Professor of internal medicine/Director of Institute Phone +381 11 2684177 Fax +381 11 2685357 Website med.bg.ac.yu Research Team Objectives Main Fields Genetics Internal Medicine We are generally involved in endocrine oncology, mostly in neuroendocrine tumors (NETs) including hereditary syndromes, multiple endocrine neoplasia type 1 and 2 (MEN 1 and MEN 2). We perform genetic screening (MENIN gene and RET proto-oncogene) in these patients and their families in a regular way. Regular screening, in patients with apparently sporadic pheochromocytoma, for known and new mutations in genes encoding succinate dehydrogenase subunits B, C and D (SDHB, SDHC and SDHD) is also performed. The role of mutations in VHL and transcriptional activity of VHL, HIF-a, and Erythropoetin genes in tumorigenesis of clear renal cell carcinoma is another project that we are interesting in. Adrenal tumors (adenomas) that are incidentally discovered seem to be associated with insulin resistance. We study therefore the role of glucocorticoid receptor gene polymorphisms (BclI, N363S and ER22/23EK) in the development of insulin resistance in patients with adrenal adenomas. We are open for the cooperation in all fields of our work and research. Partners/Interests researcher Genetics Physiology Internal Medicine 1. Partner should be able to provide patients. 2. To have facilities to performe genetic analyses or to be able to send tissue samples to our labs. 3. To enable metabolic and endocrinological assessment of patients The Impact of Glucocorticoid Receptor (GR) Gene Polymorphisms N363S, Bcl-I and ER22/23EK on Insulin Resistance in Patients with Clinically Non-Functioning Adrenal Tumors Clinically inapparent adrenal masses detected trough imaging for non-adrenal desease, are often refered to as adrenal incidentaloma, were first described 20 years ago. Despite the rarity of primary adrenal carcinoma, incidentaly discovered adrenal masses are one of the most prevalent of all tumors in humans. The prevalence of incidentalomas approches 3% in middle age, and increases to as much as 10% in the elederly. Adenomas comprise the vest majority of incidental asymptomatic adrenal masses. According to literature, up to 47% (5-47%) secrete cortisol and it seems that these patients are at increased risk for the development of metabolic syndrome. The impact of these tumors on health outcome is undetermined. This should be a prospective study. In patients with established diagnosis of so called non-functional adrenal tumor, confirmed by proper clinical (endocrine testing) and radiological evaluation (MRI or CT), the impact of GR genotype on sensitivity to glucococrticoids (GC) and insulin, and on body composition should be assessed. GCs play important role in the process of differentiation and proliferation of visceral fat tissue. On the ohter hand, the amount of visceral fat tissue is the key determinant of insulin resistance. Thus, we expect to find close relationship between GR gene polimorphisms and specific phenotypes in these patients (body composition and insulin resistance). It is likely, that we shall be able to develop specific clinical tools for the detection of patients at higher risk for development of early atherosclerosis. In all patients RFLPs, SSCP and automated sequencing techniques will be used in genotyping of GR gene in constitutive DNA (blood leukocytes). In those patients who will undergo surgery, genotyping of GR gene will be performed by using DNA obtained from normal adrenal-cortex tissue in adjacent to adrenal adenoma and from tumor tissue. In addition, transcriptional activity (mRNAs) of heat shock protein (Hsp) 70 and 90 genes and GR gene will be determined by RT PCR in tumor tissue as well as in normal adrenal cortex in adjacent to tumor. The expression of Hsp70, Hsp90 and GR in normal and tumor tissue will be determined by western blot. Body composition will be assessed by DEXA and hormonal/metabolic parameters by ELISA, RIA, IRMA and HPLC. New knowledge could be generated and its application might have some impact on health policy of every country in EU through novel pharmaceutical approach in the treatment of, not only adrenal incidentalomas but also of obesity and insulin resistance. Results of this project might add novel information to the pathogenesis of adrenal tumors and early atherosclerosis. These can be converted into social and economic benefits through prevention/retardation of both diseases. To convey this project, collaboration not only between different specialties in medicine is needed, but it also encompasses collaboration between centers of excellence all over the EU. Genetics Institution/University Name of Institution/University Institute of Endocrinology, Medical School of Belgrade Number of Employees 300 Number of Researchers 45 Country Serbia and Montenegro Postal Adress Dr Subotica 13 11000 Beograd Genetics Research Team Research Team Name Individual Researcher No Research Team Leader Name Associated Professor Visnja Lezaic Research Team Members Team Member 0 Associated Professor Visnja Lezaic [[email protected]] Team Member 1 Retired professor Ljubica Djukanovic [[email protected]] Team Member 2 M.DD. Ph. D. Milan Stosovic [[email protected]] Team Member 3 teaching assistant Radomir Naumovic [[email protected]] Team Member 4 teaching assistant Milan Radovic [[email protected]] Team Member 5 Associated Professor Sanja Simic-Ogrizovic [[email protected]] Team Member 6 Associated Professor Dijana Jovanovic [[email protected]] Research Team Projects Project Name KIDNEY DISEASES IN THE ELDERLY: DEVELOPMENT OF STRATEGY FOR EARLY DETECTION, PREVENTION AND TREATMENT Project Leader Associated Professor Višnja Ležaić [[email protected]] Project Funding Agency Ministry of Science and technology of Serbia Project Budget 20000 € Project Start Date 2006-01-01 Project End Date 2010-01-01 Project Partners University Clinical Centre, Institutes of Urology and nephrology, Department of Nephrology and Biochemistry, University of Belgrade, School of Medicine, Institutes of Biochemistry and Biology and Human Genetics, Serbia Project Summary A rapid growth in the number of elderly persons requiring dialysis therapy made the investigations of kidney diseases in the elderly very actual nephrology topic. The aim of the project is to find out the characteristics of kidney diseases in persons over 65 and to define the strategies for their early detection, prevention and treatment. The objective of the study comprises epidemiological, functional, clinical, laboratory investigations of kidney disease in elderly patients and the comparison with patients younger than 65. The investigations will reveal: 1. Prevalence of kidney disease patients over 65 treated in nephrology units in Serbia and in the primary health care units, 2. The most accurate method for estimation of global kidney function and the influence of aging, kidney diseases and comorbidity on kidney size and function, 3. Specificity of acute, chronic renal failure, ESRD and glomerular diseases in the elderly and the most effective methods for their treatment, 4. Frequency, clinical significance and possibilities for the prevention and therapy of co-morbidity in the elderly ESRD patients, 5. Mechanism contributing to atherosclerosis, the most prevalent co-morbidity in CRF 6. Association between depression, chronic inflammation, quality of life, morbidity, mortality of ESRD patients over and below 65. The investigations will allow the definition of the guidelines for the early detection, prevention and treatment of kidney diseases in the elderly in our country. Project Website Contact Person Name MD Visnja Lezaic Email [email protected] Function Chief of the department Phone +381 11 3617127 Fax +381 11 3617127 Website http://www.med.bg.ac.yu Genetics Research Team Objectives Main Fields Genetics Clinical chemistry Internal Medicine Premature atherosclerosis and cardiovascular calcifications in patients with chronic renal failure and/or treated with dialysis was driven by more than one biochemical pathway. Besides patient age, inflammation and calcium-phosphate disturbances, genes encoding various proteins (involved in the inflammatory component of atherosclerosis) have major influence The scientific excellence of the group is proven by the bibliographic entries. Major equipment for biochemical and genetic laboratory is available. Partners/Interests researcher Genetics Clinical chemistry Internal Medicine We search for researchers/ partners interested in investigations of cardiovascular disturbances in chronic renal failure patients in predialysis phase or treated with dialysis. Premature atherosclerosis and cardiovascular calcifications in patients with chronic renal failure and/or treated with dialysis was driven by more than one biochemical pathway. Besides patient age, inflammation and calcium-phosphate disturbances, genes encoding various proteins (involved in the inflammatory component of atherosclerosis) have major influence The scientific excellence of the group is proven by the bibliographic entries. Major equipment for biochemical and genetic laboratory is available. Institution/University Name of Institution/University Clinical Centre of Serbia, Institute of Urology and Nephrology Number of Employees 400 Number of Researchers 40 Country Serbia and Montenegro Postal Adress Pasterova 2 11000 Beograd Genetics Research Team Research Team Name 1. Rudjer Boskovic Institute, Division of Molecular medicine 2. Private clinic for maxillofacial surgery "Bagatin" Individual Researcher No Research Team Leader Name Assistant Professor, M.D, PhD. ENT speci Jadranka Handzic Research Team Members Team Member 0 MSc. Sandra Kraljevic [[email protected]] Team Member 1 MSc. Mirela Sedic [[email protected]] Team Member 2 Dipl.ing. Sinisa Bratulic [[email protected]] Team Member 3 Professor, PhD. M.D. Kresimir Pavelic [[email protected]] Team Member 4 Mario Bagatin [] Team Member 5 M.D, PhD. Jadranka Handzic [] Team Member 6 M.D. veterinarian Srdan Vucinic [] Contact Person Name Assistant Professor, M.D, PhD. ENT specialist Jadranka Handzic Email [email protected] Function Medical School, University of Zagreb, Faculty Phone 00 385 1 4552333 Fax 00 385 1 4552333 Website www.mef.hr Research Team Objectives Main Fields Genetics Otorhinolaryngology Functional genomics analyses of craniofacial structures in clinically well defined subgroups of patients with non-syndromic cleft lip and palate Partners/Interests researcher Genetics Otorhinolaryngology Genetics, microarray analyses, non-syndromic cleft lip and palate Non-syndromic cleft lip and palate are accompanied with developmental changes of the cranial base, retrognathic maxilla, increased pharyngeal width, smaller middle ear space, changes in petrous portion of the temporal bone, short and high positioned and clefted hard palate, hypoplastic and malpositioned cleft muscles and retarded mastoid pneumatisation with low or no tendency for growth which is in correlation with the severity of cleft lip and palate. The major consequence of these anatomical abnormalities is an increased risk of conductive hearing loss, caused by otitis media with effusion. Its long term presence leads to impairment of central auditory hearing as well as cognitive and behavioral disturbances joined with problems in speaking and social adaptability. In addition, poor detection of sounds in noisy environments and poor auditory temporal resolution are very frequent findings. Surgery of cleft lip and palate is mostly focused on reconstruction of cleft structures and aesthetic point of view with minor or no interest in functional improvement. In most patients, there is a need for secondary reconstructions and prolonged rehabilitation, which dramatically increases the cost of the whole procedure. The comprehensive effort in recognizing the etiology of most, if not all, disturbances through the research of gene polymorphisms and/ or genes activity should be the ultimative goal in this area of research. So far, there are no many information on genetic background underlying this disorder. The literature data mostly point out the polygenic disease which occurs as the consequence of interaction of harmful environmental factors with specific genetic background. One can conclude that one of the major missleading in searching for the gene/genes candidates might be lack of understanding of different clinical presentations/phenotypes in these patients. Hence, detailed study of phenotypes is the first and only valuable base for understanding the genotype. The analysis of all craniofacial abnormal anatomy features accompanied to cleft lip and palate and combined with careful re-grouping of patients is an imperative. The results of functional genetics analyses of the higest quality can answer specific question only if performed on clinically well selected patients. This is particularly important for DNA polymorphism analyses. Not only prevention, but also the treatment of cleft lip and palate should be based on multidisciplinary Genetics basic and clinical research. This approach should not help only on early recognizing of this disorder, but will also lead to efficient therapy in routine clinical work which is a guarantee for better health and social integration. These goals can be accomplished only through comprenhensive genomic and proteomic research. Institution/University Name of Institution/University Medical School, University of Zagreb Number of Employees 500 Number of Researchers 300 Country Croatia Postal Adress Salata 4 10000 Zagreb Genetics Research Team Research Team Name Asthma Genomics Individual Researcher No Research Team Leader Name DSc Csaba Szalai Research Team Members Team Member 0 MSc Ildiko Ungvari [[email protected]] Team Member 1 MSc Gergely Tolgyesi [[email protected]] Team Member 2 PhD, MD Adrienne Nagy [[email protected]] Team Member 3 MSc Marton Keszei [[email protected]] Research Team Projects Project Name Genetic background of Asthma Project Leader DSc Csaba Szalai [[email protected]] Project Funding Agency OTKA,. ETT Project Budget 28000 € Project Start Date 2004-01-01 Project End Date 2008-12-31 Project Partners Hungary/Semmelweis Univ/DGCI Hungary/Heim Pal Hospital/Mol Biol Lab Hungary/Hungarian Academy of Sciences/Res group of Immunogenomics Project Summary Asthma genetics and genomics Aim: 1. With the help of large number of asthmatic and healthy patients and SNP screening methods we would like to identify genes and genetic variations playing roles in the pathomechanism of and susceptibility to asthma. A Core Facility for high throughput SNP screening (GenomeLab SNPstream with the capacity of several million SNPs in a day) is available for us, which provides the possibility to identify unknown genes or genome areas in asthma. These genes and their protein products are potential biomarkers and drug targets in asthma and provide the possibility for development of novel diagnostic and therapeutical methods. 2. We are going to set an in vivo method based on the technique of RNA interference, with which we will be able to study the role of different genes in an in vivo animal model of asthma. With this method, we will be able to, at least partly, substitute the expensive and time consuming gene knock out method. With the help of this method it can be possible to study the functions and roles of genes detected in the SNP screenings. 3. With the help of the optimized RNAi method, results of gene expression measurements and SNP screens, it can be possible to assign new therapeutical (or even gene therapeutical) targets in asthma. Working plan: 1.1 At present in our asthma biobank there are samples and clinical data from 230 asthmatic children available for us, and we would like to increase this collection by 100 DNA samples per annum. 1.2. The first genome area we are going to screen is the 11q13. Next we plan to screen additional genome areas (e.g. 12q14.3-q24.31, 13q14, 14q11.2-q13, 17q11.2) as well as carry out SNP screenings in candidate genes identified through literature screening. 1.3. The first task in our RNAi experiments to verify the effectiveness of the intratracheal delivery by fluorescencelabeled non-gene specific control siRNA, and confirm that with this method the siRNA molecule gets really to the lung as a target organ of the animal. Then with the help of our protocol we make the mice producing symptoms similar to human asthma, and threat the animals with siRNA specific for important asthma genes. With different methods (e.g. measurement of airway hyperreactivity, lung histochemistry, investigation of BAL cells with FACS etc.) we study the effect of RNAi therapy to the symptoms and parameters of the animals. Among our plans there is a high throughput gene expression measurement in the Agilent Microarray Core Facility, also in the area of the institute. With the help of gene expression chips we would like to follow the changes of the gene expression in the lung of the animals throughout these processes. 1.4. We would like to utilize the results from the whole genome gene expression microarray experiments in our candidate gene (pathway) association studies, i.e. we compare the SNP patterns found in asthmatic patients in these genes with those found in healthy controls. Project Website www.dgci.sote.hu Contact Person Name DSc Csaba Szalai Email [email protected] Genetics Function PI Phone 361-210-2930/6502 Fax 361-303-6968 Website www.dgci.sote.hu Research Team Objectives Main Fields Genetics Paediatrics Pharmacology Aim: 1. With the help of large number of asthmatic and healthy patients and SNP screening methods we would like to identify genes and genetic variations playing roles in the pathomechanism of and susceptibility to asthma. A Core Facility for high throughput SNP screening (GenomeLab SNPstream with the capacity of several million SNPs in a day) is available for us, which provides the possibility to identify unknown genes or genome areas in asthma. These genes and their protein products are potential biomarkers and drug targets in asthma and provide the possibility for development of novel diagnostic and therapeutical methods. 2. We are going to set an in vivo method based on the technique of RNA interference, with which we will be able to study the role of different genes in an in vivo animal model of asthma. With this method, we will be able to, at least partly, substitute the expensive and time consuming gene knock out method. With the help of this method it can be possible to study the functions and roles of genes detected in the SNP screenings. 3. With the help of the optimized RNAi method, results of gene expression measurements and SNP screens, it can be possible to assign new therapeutical (or even gene therapeutical) targets in asthma. Working plan: 1.1 At present in our asthma biobank there are samples and clinical data from 230 asthmatic children available for us, and we would like to increase this collection by 100 DNA samples per annum. 1.2. The first genome area we are going to screen is the 11q13. Next we plan to screen additional genome areas (e.g. 12q14.3-q24.31, 13q14, 14q11.2-q13, 17q11.2) as well as carry out SNP screenings in candidate genes identified through literature screening. 1.3. The first task in our RNAi experiments to verify the effectiveness of the intratracheal delivery by fluorescence-labeled non-gene specific control siRNA, and confirm that with this method the siRNA molecule gets really to the lung as a target organ of the animal. Then with the help of our protocol we make the mice producing symptoms similar to human asthma, and threat the animals with siRNA specific for important asthma genes. With different methods (e.g. measurement of airway hyperreactivity, lung histochemistry, investigation of BAL cells with FACS etc.) we study the effect of RNAi therapy to the symptoms and parameters of the animals. Among our plans there is a high throughput gene expression measurement in the Agilent Microarray Core Facility, also in the area of the institute. With the help of gene expression chips we would like to follow the changes of the gene expression in the lung of the animals throughout these processes. 1.4. We would like to utilize the results from the whole genome gene expression microarray experiments in our candidate gene (pathway) association studies, i.e. we compare the SNP patterns found in asthmatic patients in these genes with those found in healthy controls. Partners/Interests researcher industrial partner Genetics Pharmacology Paediatrics We are looking for partner, who can participate in our partial genome screening project in asthma, with additional asthmatic patients (children, or families), or bioinformatics who would be able to help us to evaulate or SNP results. Or we are looking for partner, with whom we could cooperate in our RNAi researches. Asthma genetics and genomics Aim: 1. With the help of large number of asthmatic and healthy patients and SNP screening methods we would like to identify genes and genetic variations playing roles in the pathomechanism of and susceptibility to asthma. A Core Facility for high throughput SNP screening (GenomeLab SNPstream with the capacity of several million SNPs in a day) is available for us, which provides the possibility to identify unknown genes or genome areas in asthma. These genes and their protein products are potential biomarkers and drug targets in asthma and provide the possibility for development of novel diagnostic and therapeutical methods. 2. We are going to set an in vivo method based on the technique of RNA interference, with which we will be able to study the role of different genes in an in vivo animal model of asthma. With this method, we will be able to, at least partly, substitute the expensive and time consuming gene knock out method. With the help of this method it can be possible to study the functions and roles of genes detected in the SNP screenings. 3. With the help of the optimized RNAi method, results of gene expression measurements and SNP screens, it can be possible to assign new therapeutical (or even gene therapeutical) targets in asthma. Working plan: 1.1 At present in our asthma biobank there are samples and clinical data Genetics from 230 asthmatic children available for us, and we would like to increase this collection by 100 DNA samples per annum. 1.2. The first genome area we are going to screen is the 11q13. Next we plan to screen additional genome areas (e.g. 12q14.3-q24.31, 13q14, 14q11.2-q13, 17q11.2) as well as carry out SNP screenings in candidate genes identified through literature screening. 1.3. The first task in our RNAi experiments to verify the effectiveness of the intratracheal delivery by fluorescencelabeled non-gene specific control siRNA, and confirm that with this method the siRNA molecule gets really to the lung as a target organ of the animal. Then with the help of our protocol we make the mice producing symptoms similar to human asthma, and threat the animals with siRNA specific for important asthma genes. With different methods (e.g. measurement of airway hyperreactivity, lung histochemistry, investigation of BAL cells with FACS etc.) we study the effect of RNAi therapy to the symptoms and parameters of the animals. Among our plans there is a high throughput gene expression measurement in the Agilent Microarray Core Facility, also in the area of the institute. With the help of gene expression chips we would like to follow the changes of the gene expression in the lung of the animals throughout these processes. 1.4. We would like to utilize the results from the whole genome gene expression microarray experiments in our candidate gene (pathway) association studies, i.e. we compare the SNP patterns found in asthmatic patients in these genes with those found in healthy controls. Institution/University Name of Institution/University Semmelweis University Department of Genetics Cell and Immunobi Number of Employees 35 Number of Researchers 20 Country Hungary Postal Adress Nagyvarad ter 4 1089 Budapest Genetics Research Team Research Team Name Bone and Soft Tissue Sarcomas & Bone Metastases Individual Researcher Yes Research Team Leader Name Prof. Dr. Andreas Leithner Contact Person Name Prof. Dr. Andreas Leithner Email [email protected] Function Assistant Head and Chair of the Department of Orthopaedic Surgery Phone +43 316 385 81899 Fax +43 316 385 4806 Website www.meduni-graz.at/orthopaedie/ Research Team Objectives Main Fields Genetics Pathology Surgery interdisciplinary research on bone and soft tissue sarcomas / bone and soft tissue metastases Partners/Interests researcher Pathology Surgery Genetics cooperation scoring systems for bone metastases using biological markers Institution/University Name of Institution/University Medical University Graz Number of Employees n.a. Number of Researchers n.a. Country Austria Postal Adress Auenbruggerplatz 5 8036 Graz Genetics Research Team Research Team Name Forensic DNA laboratory, Institute of forensic Medicine Individual Researcher No Research Team Leader Name PhD Oliver Stojkovic Research Team Members Team Member 0 assistant professor Oliver Stojkovic [[email protected]] Team Member 1 MD Aleksandar Stanojevic [[email protected]] Team Member 3 DNA analyst Tatjana Varljen [[email protected]] Research Team Projects Project Name Structure of genetic variation of microsatelite loci in ethnic comunities in Serbia and Montenegro Project Leader PhD Oliver Stojkovic [[email protected]] Project Funding Agency Ministry of sciences Republic of Serbia Project Budget 10.000 € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Serbia and MOntenegro / University of Novi Sad / Institute of Forensic Medicine Serbia and Montenegro / University of Kragujevac / Institute of Pathology and Forensic Medicine Serbia and Montenegro / University of Nis / School of Medicine, Division of Forensic Medicine Project Summary Detailed understanding of spatial and ethnical organization of genetic variability in humans can provide valuable information for genetic epidemiology (on the reasons of differential incidence of certain diseases in various ethnical groups), as well as for anthropology and evolutionary biology (on mechanisms that have shaped evolutionary history of our species, and demographic history of local populations). In this project, we will genotype more than a 1000 human samples. Sampling will be based on regional birthplace location and self reported ethnicity. Our previous studies were based on the unstructured population from Serbia and Montenegro. In this project, we will take into account the fact of historical and demographic heterogeneity of Serbia and Montenegro general population, so the observed genetic variability will be partitioned into its ethnical and spatial component, by population genetic statistics (AMOVA, F statistics, D statistics, gene genealogies). Considering that our community has recently passed through several consecutive bottleneck episodes, in both world wars, we will be able to test if these historical events left marks on genetic structure of our community. Knowledge of geographical and ethnical origin of tested subjects, alone and with regard to data from other European populations, will allow us to describe and determine patterns of spatial genetic variation, migration, gene flow, population subdivision and population level medical associations. Project Website www.med.bg.ac.yu Contact Person Name PhD Oliver Stojkovic Email [email protected] Function Head of DNA laboratory Phone +381113617931 Fax +381-11-3617931 Website www.med.bg.ac.yu Research Team Objectives Main Fields Genetics Biology molecular anthropology, Forensic genetics, DNA typing, human population genetics, ancient DNA, degraded DNA Genetics Partners/Interests researcher Genetics Biology Access to DNA samples or the ability to collect DNA samples from ethnical groups involved in the future research. Population genetics studies in ethnical groups living in the Southern Europe area, such as Roman (Gypsies) populations Institution/University Name of Institution/University University of Belgrade Number of Employees 10000 Number of Researchers 5000 Country Serbia and Montenegro Postal Adress Studentski trg 16 11000 Belgrade Genetics Research Team Research Team Name Genetic epidemiology and pharmacogenomics Individual Researcher No Research Team Leader Name Dr Dragan Alavantic Research Team Members Team Member 0 PhD Dragan Alavantic [[email protected]] Team Member 1 PhD Olga Jozanov-Stankov [[email protected]] Team Member 2 PhD Aleksandra Stankovic [[email protected]] Team Member 3 PhD Maja Zivkovic [[email protected]] Team Member 4 Mr Sci Tamara Djuric [[email protected]] Team Member 5 Bs Sci Sanja Mecanin [[email protected]] Team Member 6 Bs Sci Aleksandar Rakovic [[email protected]] Team Member 7 Bs Sci Olja Stancic [[email protected]] Research Team Projects Project Name Genetic epidemiology and pharmacogenomics of vascular diseases Project Leader Dr Dragan Alavantic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary Research are focused on investigation of primary gene structure in healthy subjects and in groups of patients with vascular diseases (cardiovascular, cerebrovascular, renovascular) and certain neurodegenerative diseases. Objects are key genes involved in lipid metabolism, regulation of blood pressure, extracellular matrix remodeling, inflammation and oxidative stress. The structure and population specificity of genes for: apolipoproteins (A,B,C,E); LPL, LDLR, CETP, PPaR(a,g), ENPP1, RAS (ACE,ACE2, AT1R,AT2R,AGT), MMPs, and proteins involved in inflammatory cascade and oxidative stress (IL-6, MCP-1, IL-1beta, IL-1ra, NOS-3, GPx4,flGST,PON1) by establishing (1)genotype and allele frequency of the genes in both healthy population and different groups of patients, (2)haplotype effects as well as risk factors on: gene expression, phenotype, and chosen therapy. The goal-a new knowledge obtained by investigation of primary gene structure in population of Serbia, which should be stimulating for introducing pharmacogenetics in clinical practice. Research goal in the first two years of the project is, by determination of the relationship between primary structure and expression of the genes, taking into consideration risk factors, to define persons at the highest risk. Well defined predictive factors should be then made possible for an investigation of proper diagnostics, prevention and therapy certain groups of patients which suffered from the most frequent diseases in Serbia Project Website mntr.sr.gov.yu Contact Person Name Dr Dragan Alavantic Email [email protected] Function Head of project Phone +381 11 2447485 Fax +38 11 2447485 Website vin.bg.ac.yu Research Team Objectives Main Fields Genetics Epidemiology Clinical chemistry Genetics Gene candidate DNA polymorphisms and their association with vascular diseases, main risk factors (dislipidaemia, hypertension, diabetes, smoking ..) as well as certain renal and neurodegenerative disease.. Population (case-control) and family studies, both genotype and allele frequencies, genegene and gene-environment relationship, haplotyping, development of methods for clinical use. Partners/Interests researcher Genetics Clinical chemistry Epidemiology from institutes and clinics Genetic epidemiology of stroke Genetics of oxidative stress Institution/University Name of Institution/University VINCA Institute of Nuclear Sciences Number of Employees 750 Number of Researchers 400 Country Serbia and Montenegro Postal Adress POBox 522 522 11001 Belgrade Genetics Research Team Research Team Name Human genetics and pharmacogenomics Individual Researcher Yes Research Team Leader Name Assistant Prof., PhD Uroš Potočnik Research Team Projects Project Name Genetic susceptibility to gastrointestinal complex diseases and pharmacogenomics Project Leader Assistant Prof., PhD Uroš Potočnik [[email protected]] Project Funding Agency Project Budget € Project Start Date 2005-09-01 Project End Date 2008-08-31 Project Partners 1. Slovenia/University of Maribor, Faculty of Electrical Engineering and Computer Science/Laboratory for system design 2. Slovenia/University of Ljubljana, Faculty of Medicine/Department for molecular genetics 3. Slovenia/University of Ljubljana, Faculty of Medicine/Institute for microbiology 4. Slovenia/Taeching Hospital Maribor/Medical departments Project Summary The aim of our study is to provide new molecular diagnostic markers and molecular targets for novel drugs design for better prevention and treatment of complex gastrointestinal diseases. Project Website http://sicris.izum.si/search/prj.aspx?opt=3&l Project Name Molecular genetic and pharmacogenomic markers in complex gastrointestinal diseases Project Leader Assistant Prof., PhD Uroš Potočnik [[email protected]] Project Funding Agency ARRS & NIH Project Budget 25000 € Project Start Date 2006-03-01 Project End Date 2008-02-28 Project Partners 1. USA/ National Institutes of Health, National Cancer Institute/Laboratory of genomic diversity 2. Slovenia/University of Maribor, Faculty of Electrical Engineering and Computer Science/Laboratory for system design 3. Slovenia/University of Ljubljana, Faculty of Medicine/Department for molecular genetics Project Summary Particularly focus of our study is to provide new molecular targets and molecular diagnostic markers including Single nucleotide polymorphisms (SNPs), haplotypes and expression profiles, for novel drugs design for better prevention and treatment of complex gastrointestinal diseases. Project Website under construction Contact Person Name Assistant Prof., PhD Uroš Potočnik Email [email protected] Function Head of Centre for human genetics and pharmacogenomics Phone + 386 2 234 56 01 Fax + 386 2 23 45 600 Website www.mf.uni-mb.si Research Team Objectives Main Fields Genetics Human genetics and pharmacogenomics Genetics Partners/Interests researcher industrial partner Suitable Genetics Biochemistry Microbiology 1. SUSCEPTIBILITY GENES AND PHARMACOGENOMIC MARKERS IN COMPLEX DISEASES The aim of our study is to identify genes, single nucleotide polymorphisms (SNPs) and haplotypes associated with complex diseases including both major forms of inflammatory bowel diseases (IBD), ulcerative colitis and Crohn disease, IBD-associated neoplasia (IBDNs), colorectal cancer (CRC), asthma, aspirin intolerance, diabetes, cardio-vascular diseases, schizophrenia. We will establish a comprehensive follow-up patients database and bioinformatic tools for finding statistical correlations between molecular genetic and clinicopathological data including treatment response. We will also determine the gene expression profiles in blood leucocytes and colon biopsies taken from IBD patients during standard treatment with corticosteroids and immunosuppresives and treatment with monoclonal antibody inhibitor against TNF alfa (Inflaximab) and correlate results with treatment response. We will use combination of different approaches in our disease association and pharmacogenomic studies including candidate gene approach, genome-wide haplotype and linkage disequilibrium association approaches and disease pathway analysis to characterize genetic risk factors predisposing to complex diseases and treatment response. Our particular focus will be on identification of functional SNPs in regulatory cis-acting regions and describing their role in differential gene expression and disease association. We will develop new approach for identification of functional SNPs in regulatory cis-acting regions based on allele specific expression in lymphoblastoid cell lines from CEPH families and segregation analysis. The database with genes showing most significant allele specific expression will be used for our disease association study and will be available on the internet to scientific community for other disease association studies. Identified SNPs in regulatory cis-acting regions will be used for identification of transcription factors. Alele specific expression will be compared between cell lines and different tissues including colon, IBDNs, colon adenomas and colorectal tumors. The alternative splice variants expressed in different tissues and pathogenic states will be described. We will also describe molecular alterations, including somatic mutations, methylation status and global gene expression profile in adenomas from IBDN patients, tumors from CRC patients and biopsies from IBD patients during treatment. We will correlate genetic data with CRC patients prognosis and survival. We will functionally characterize genes and proteins most significantly associated with disease. We will develop new bioinformatic and statistical genetic tools for best candidate gene selection..We will use oligo-microarrays, quantitative real time PCR (Taqman) and imunohistochemistry for expression profiling. We will use gel-mobility shift assay for identification of transcription factors associated with SNPs in regulatory regions. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Genetics Research Team Research Team Name Laboratory for Human Genetics, INGEB Individual Researcher No Research Team Leader Name Msc Lejla Kapur Research Team Members Team Member 0 Mrs Drazenka Macic [[email protected]] Team Member 1 Mr Jasmin Ramic [[email protected]] Team Member 2 Mrs Naida Lojo-Kadric [[email protected]] Team Member 3 Dr Naris Pojskic [[email protected]] Team Member 4 MSc Lejla Kapur [[email protected]] Research Team Projects Project Name establishment of research basis for genetic characterization of common cancers in B&H Project Leader prof dr Nermina Obralic [[email protected]] Project Funding Agency Ministry of Science, Sarajevo Canton Project Budget 10000 € Project Start Date 2004-07-31 Project End Date 2006-07-31 Project Partners Bosnia and Herzegovina, Institute for Genetic Engineering and Biotechnology, Sarajevo / Laboratory for Human genetics Bosnia and Herzegovina, University Clinical Centre, Institute of Oncology Bosnia and Herzegovina, University Clinical Centre, Institute of Pathology Project Summary Overall aim of this project is to establish research basis and biobank for future molecular-genetic research of etiology and farmacotherapeutic response in several common cancers in Bosnia and Herzegovina. Main activities are related to optimization and validization of protocols for collection, transport, DNA and RNA isolation, preservation and archiving of tumor tissue specimens. All relevant data for patients (general, clinical, familial and therapeutically-related) are gathered into an electronic biodatabase that is linked to genomic databank. Complete archive will serve in future genotypephenotype correlation studies. Currently it contains completed data for about a hundred specimens of cancerous and precancerous tissue from breast, ovary and colon. Project Website Project Name Identification of DNA markers for predisposing factors of schizophrenia in patients from B&H; Project Leader MSc Lejla Kapur [[email protected]] Project Funding Agency Project Budget € Project Start Date 2004-12-01 Project End Date 2007-12-01 Project Partners Bosnia and Herzegovina, Institute for Genetic Engineering and Biotechnology, Sarajevo, Laboratory for Human genetics Bosnia and Herzegovina, University Clinical Center Sarajevo, Psychiatric Clinic Bosnia and Herzegovina, Institute for Genetic Engineering and Biotechnology, Sarajevo, Laboratory for Bioinformatics and Biostatistics Project Summary Case control study was performed to assess allelic, genotype and haplotype analysis of ten genomewide polymorphic markers with shizophrenia in cohort of 104 individuals: age, sex and ethnically matched. Standard genotyping methodology, PCR-RFLP and microsatelite analysis was used. Extensive population genetics analysis was performed using genotype an phenotype data. Project Website Genetics Contact Person Name Lejla Kapur Email [email protected] Function Scientific Secretary Phone +38733220926,215778 Fax +38733442891 Website ingeb.ba Research Team Objectives Main Fields Genetics Information Technology, Statistics, Documentation gene expression and structural analysis in common cancers; psychiatric genetics Partners/Interests researcher Genetics Epidemiology access to patients expertise in one of listed fields (stages of project): 1. patients recruitment using operationalised research criteria (for selected disorder) and general, clinical and therapeutic data collection; 2. DNA, RNA, protein isolation, preservation and storage 3. one of bioogical level analysis (genomic, transcription or expression) 4. extensive biostatistical analysis of relevant biological data Regional Network for Genetics of Complex Disorders (Cancers and Neurodegenerative ilnesses) Institution/University Name of Institution/University Institute for Genetic Engineering and Biotechnology Number of Employees 20 Number of Researchers 16 Country Bosnia and Herzegovina Postal Adress Kemalbegova 10 71000 Sarajevo Genetics Research Team Research Team Name Molecular basis of atherogenesis research team Individual Researcher No Research Team Leader Name PhD Goran Ferencak Research Team Members Team Member 0 BSc Natalija Marinkovic [[email protected]] Team Member 1 Assistant Professor Ksenija Vitale [[email protected]] Team Member 2 PhD Ljubica Vranic Stavljenic [] Team Member 3 PhD Branka Grskovic [[email protected]] Team Member 4 Professor Ana Stavljenic Rukavina [[email protected]] Team Member 5 PhD Daria Pasalic [[email protected]] Team Member 6 PhD Jasna Lenicek-Krleza [[email protected]] Team Member 7 MSc Ana Bronic [[email protected]] Team Member 8 PhD Lorena Honovic [[email protected]] Team Member 9 Assistant Professor Robert Bernat [[email protected]] Research Team Projects Project Name Molecular basis of atherogenesis Project Leader PhD Goran Ferencak [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-10-01 Project End Date 2011-10-01 Project Partners USA/Roche Molecular Systems Inc./Institute for Human Genetics Project Summary Atherosclerotic process which underlies pathobiochemical basis of cardiovascular diseases is determined by a number of environmental and hereditary factors. The recognition of these factors is crucial for medical intervention in patients, but also for primary prevention. More than one biochemical pathway is included in the pathogenesis of atherosclerosis. Genes encoding various proteins within these biochemical pathways are candidate genes for premature atherosclerosis susceptibility markers. Included in this project research are candidate gene polymorphisms not studied in previous research no. 108247: genes coding for molecules involved in the inflammatory component of atherosclerosis and genes which may influence the concentration of triglycerides (apolipoprotein A5 gene; fatty acid binding protein, FABP-2; toll-like receptor gene, TLR-2; plateletendothelial cell adhesion molecule gene, PECAM-1; interleukin 6 and 12 genes, IL-6 and IL-12; monocyte chemoattractant protein 1 gene, MCP-1 and gene for its receptor CCR2). The second phase of the project is dealing with influence of previously genotyped polymorphisms on clinical outcome in patients after stenting. Previous research has shown that CETP (cholesteryl-ester transfer protein) gene polymorphisms influence the risk for coronary heart disease and concentrations of HDL and apolipoprotein A-I. Therefore, in the new reasearch the influence of different concentrations of mildly and completely oxidized LDL in the presence of antisense CETP-oligonucleotides in a range of concentrations on CETP gene expression and mass will be studied in HepG2 and mononuclear cells from peripheral blood in cell culture. Since environmental factors significantly influence atherogenesis, it is presumed that there is a difference in risk for atherosclerosis development regarding the present xenobiotics and it will be evaluated in subjects from general population in Koprivnièko-križevaèka county. If there is a difference in incidence of atherosclerosis between exposed and non-exposed population, it is possible that polymorphisms in genes involved in biotransformation of xenobiotics (cytochrome P450 1A1, CYP1A1, and multidrug resistance gene, MDR1) are associated with different risks for atherosclerosis development. Project Website Contact Person Name PhD Goran Ferencak Email [email protected] Genetics Function Clinical chemistry and laboratory medicine specialist Phone +38598411475 Fax +38514590236 Website Research Team Objectives Main Fields Genetics Clinical chemistry Epidemiology Atherosclerotic process which underlies pathobiochemical basis of cardiovascular diseases is determined by a number of environmental and hereditary factors. The recognition of these factors is crucial for medical intervention in patients, but also for primary prevention. More than one biochemical pathway is included in the pathogenesis of atherosclerosis. Genes encoding various proteins within these biochemical pathways are candidate genes for premature atherosclerosis susceptibility markers. Included in this project research are candidate gene polymorphisms not studied in previous research no. 108247: genes coding for molecules involved in the inflammatory component of atherosclerosis and genes which may influence the concentration of triglycerides (apolipoprotein A5 gene; fatty acid binding protein, FABP-2; toll-like receptor gene, TLR-2; plateletendothelial cell adhesion molecule gene, PECAM-1; interleukin 6 and 12 genes, IL-6 and IL-12; monocyte chemoattractant protein 1 gene, MCP-1 and gene for its receptor CCR2). The second phase of the project is dealing with influence of previously genotyped polymorphisms on clinical outcome in patients after stenting. Previous research has shown that CETP (cholesteryl-ester transfer protein) gene polymorphisms influence the risk for coronary heart disease and concentrations of HDL and apolipoprotein A-I. Therefore, in the new reasearch the influence of different concentrations of mildly and completely oxidized LDL in the presence of antisense CETP-oligonucleotides in a range of concentrations on CETP gene expression and mass will be studied in HepG2 and mononuclear cells from peripheral blood in cell culture. Since environmental factors significantly influence atherogenesis, it is presumed that there is a difference in risk for atherosclerosis development regarding the present xenobiotics and it will be evaluated in subjects from general population in Koprivnièko-križevaèka county. If there is a difference in incidence of atherosclerosis between exposed and non-exposed population, it is possible that polymorphisms in genes involved in biotransformation of xenobiotics (cytochrome P450 1A1, CYP1A1, and multidrug resistance gene, MDR1) are associated with different risks for atherosclerosis development. Partners/Interests researcher industrial partner Genetics Clinical chemistry Epidemiology Influence of newly developed drugs on atherogenic mechanisms (in cell culture) Influence of genotypes in atherosclerosis candidate genes on efficiency of newly developed drugs Institution/University Name of Institution/University Zagreb University School of Medicine Number of Employees 700 Number of Researchers 100 Country Croatia Postal Adress Salata 3 10000 Zagreb Genetics Research Team Research Team Name Oral Biology Group Individual Researcher No Research Team Leader Name PhD, professor Jelena Milasin Research Team Members Team Member 0 assistant Gavrilo Brajovic [[email protected]] Team Member 1 assistant-professor Dusan Pavlica [] Team Member 2 assistant Ana Pucar [[email protected]] Team Member 3 assistant Branka Popovic [[email protected]] Contact Person Name PhD, professor Jelena Milasin Email [email protected] Function Vice-dean Phone +381 11 2685 288 Fax +381 11 2685 361 Website stomf.bg.ac.yu Research Team Objectives Main Fields Genetics Microbiology Dentristry Main research fields: 1) molecular genetics of oral malignancies and premalignant lesions of the head and neck region; 2) etiopathogenesis of periodontal disease Partners/Interests researcher Microbiology Genetics Dentristry competencies in molecular biology and microscopy (electron and laser) Establishing the connection between periodontal disease and atherosclerosis. Comparative study of periodontopathogens present in dental pockets and atherosclerotic vessels in patients undergoing vascular surgery. Institution/University Name of Institution/University School of Dentistry, University of Belgrade Number of Employees 440 Number of Researchers 180 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Genetics Research Team Research Team Name polymorphism in orthopaedics research team Individual Researcher No Research Team Leader Name Dr. Heimo Clar Research Team Members Team Member 0 Ass. Dr. Gerald Gruber [[email protected]] Team Member 1 Prof. Dr. Andreas Leithner [[email protected]] Team Member 2 Ass. Dr. Heimo Clar [[email protected]] Research Team Projects Project Name polymorphisms in orthopaedics Project Leader dr heimo clar [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-05-01 Project End Date 2010-05-01 Project Partners Project Summary creating a genetic data base and doing relevant research in bone and joint metabolism and diseases Project Website Contact Person Name dr. heimo clar Email [email protected] Function ass. Phone +43 316 385 80484 Fax +43 316 385 2957 Website meduni-graz.at Research Team Objectives Main Fields Genetics Microbiology Surgery polymorphisms could be relevant in the understanding and treatment of orthopaedic diseases. Partners/Interests researcher industrial partner Microbiology Genetics Surgery interest in an cooperation for basic research in bone and joint metabolsm and diseases finding research partners Institution/University Name of Institution/University department of orthopaedic surgery, medical university of graz Number of Employees 17 Number of Researchers 15 Country Austria Postal Adress Auenbruggerplatz 5-7 8036 graz Genetics Research Team Research Team Name Translational Medicine Group Individual Researcher No Research Team Leader Name dr Oliver Vugrek Research Team Members Team Member 0 Dr Oliver Vugrek [[email protected]] Team Member 1 dipl. ing Robert Beluzic [[email protected]] Research Team Projects Project Name S-Adenosylhomocysteine hydrolase deficiency: Molecular mechanisms of a new disease in human Project Leader Dr Oliver Vugrek [[email protected]] Project Funding Agency Project Budget € Project Start Date 2007-01-01 Project End Date 2009-12-31 Project Partners Project Summary The molecular basis for SAHH deficiency has not yet been resolved. DNA analysis of individuals with extremely high levels of SAH showed a total of 5 different not yet characterized point mutations in the SAHH gene: two point mutations, a premature stop codon and a missense mutation in 2 infants (Baric et al, 2004, 2005), two missense mutations in an adult with severe mental retardation (Buist et al 2006), and two missense mutations in a newborn causing death at the age of 4 month (unpublished data). Additionaly, we have linked another polymorphism in the SAHH gene (Gellekink et al. 2004) to three phenotypically yet inconspicuous individuals (unpublished data).To elucidate the impact of these particular point mutations on the enzymatic activity of SAHH, we constructed expression vectors and analyzed the biochemical properties of recombinant S-Adenosylhomocysteine hydrolase. The bestcharacterized missense mutation so far is a tyrosine to cysteine exchange (p.Y143C), which represents a temperature sensitive mutation. Namely, heterologous expression of mutant protein at permissive temperature results in protein with reduced enzymatic activity compared to wildtype, whereas expression at restrictive temperature yields in completely nonfunctional protein. Circular dichroism analysis of the p.Y143C mutant protein showed a significantly reduced unfolding temperature of 7°C if compared to wildtype protein. Accordingly, dynamic light scattering experiments showed accellerated aggregation of mutant protein at rising temperature. Native polyacrylamide gel electrophoresis showed, that mutant p.Y143C SAHH subunits are able to form the tetrameric complex as is the wildtype enzyme. Nevertheless, the aminoacid exchange of tyrosine to cysteine probably leads to the loss of a hydrogen bond with glutamic acid 115, which might be essential for proper subunit folding or substrate binding. The catalytic rates in direction of SAH hydrolysis or synthesis are decreased to approx. 30% if compared to recombinant wildtype SAHH. Km values of mutant protein are decreased accordingly. Quantitative binding of co-factor NAD is not affected in p.Y143C, but there is a dramatic change in the oxidation states, i.e. mutant protein contains mainly NADH (80%), whereas wildtype protein contains approx. 90% NAD+. The NADH accumulation indicates that protons involved in the oxidation reactions are leaking from the active site rather than being retained as is the case for wildtype SAHH. Project Website www.irb.hr/korisnici/~ovugrek/home1.htm Contact Person Name dr Oliver Vugrek Email [email protected] Function Research associate Phone +384-1-4560946 Fax +385-1-4680119 Website http://www.irb.hr/korisnici/ovugrek/home1.htm Genetics Research Team Objectives Main Fields Genetics Biochemistry Biology S-adenosylhomocysteine hydrolase (SAHH) catalyzes the reversible hydrolysis of Sadenosylhomocysteine (SAH) to adenosine (Ado) and L-homocysteine (Hcy). In eukaryotes, this is the major route for disposal of the SAH formed as a product of many S-adenosylmethionine (SAM)dependent methyltransferases. Thus, SAH hydrolysis is believed to play a critical role in the regulation of biological methylation, which on the other hand is important for post-translational modifications. Accordingly, protein methylation is important for protein-protein interactions, cellular localization and maturation of heterogeneous ribonucleoproteins and it might be crucial in cellular signaling and viral replication. Also, methylation is an important part of the histone code that regulates cell type–specific gene expression programs. Interestingly, aberrant methylation is a widespread phenomenon in cancer and may be among the earliest changes during oncogenesis.Aberrant methylation processes might be the reason for the severe pathologic effect of the new genetic disorder of SAHH deficiency in human. Namely, SAHH deficiency results in an intracellular accumulation of SAH (150-fold) and SAM (30-fold), causing a significant imbalance in the intracellular SAH/SAM ratio in patients. SAH is a strong competitive inhibitor of many SAM-dependent methyltransferases. Therefore, the significant imbalance in the SAM/SAH ratio in SAHH deficient patients might be the reason for other abnormalities such as myopathy, retarded psychomotor development and signs of mental retardation (Baric et al, 2004). Further, bioinformatics results from the human genome project show that there exist a large number of methyltransferases, but their substrates have not been characterised yet. Methylation may thus be far more important than previously thought, which is consistent with the severe pathologic effect of SAHH deficiency. The molecular basis for SAHH deficiency has not yet been resolved. DNA analysis of individuals with extremely high levels of SAH showed a total of 5 different not yet characterized point mutations in the SAHH gene. To elucidate the impact of these particular point mutations on the enzymatic activity of SAHH, we constructed plasmid expression vectors for a detailed analysis of the biochemical properties of mutated recombinant SAHH. The functional analysis will allow conclusions about the involvement of the identified mutations in protein activity and herein serve as basis for our hypothesis that irregular methylation processes caused by inactivation of S-Adenosylhomocysteine hydrolase are the reason for the severe pathologic effect of the new genetic disorder of SAHH deficiency in human. Partners/Interests researcher industrial partner Biochemistry Genetics Clinical chemistry Anything which suits our research area described under project ideas etc. We have outlined two major research objectives, which can be divided into a functional genomics section and a proteomics section. Functional genomics will allow insights on the impact of 5 distinct point mutations on structure and function of S-adenosylhomocysteine hydrolase. Namely, several individuals with extremely high levels of SAH share not yet characterized point mutations in the SAHH gene. The severeness of the disease is variable and causes serious health problems with a possible lethal outcome if some of the point mutations occur in combination. To elucidate the impact of each of the point mutations on the enzymatic activity of SAHH, we will produce recombinant protein for functional analysis. Using plasmid expression vectors and heterologous expression in bacteria we have identified a temperature sensitive mutation. Accordingly, we will be analysing the remaining 4 point mutations in the SAHH gene to explain the mechanisms which underlie enzyme inactivation. We have established biochemical assays for measuring enzyme activity and co-factor NAD+/NADH content. Methods such as circular dichroism analysis and dynamic light shattering will be used for questioning temperature dependent behaviour of mutant protein. We will perform gene expression studies on DNA and RNA extracted from the fibroblast cell line obtained from patients. The thermosensitive nature of one of the mutation allows an experimental design, which uses cultured cells grown at different temperatures, i.e. permissive and restrictive temperature. DNA microarray analysis will be performed by using the most comprehensive human genome microarray, which contains complete coverage for the analysis of over 47,000 transcripts. Data analysis is performed by computational tools and software provided by the manufacturer of the microarrays. Differences in expression profiles are catalogued and used to build pathways to cellular processes involving SAHH and its role in methylation processes or their regulation. The inhibitory effects of elevated intracellular SAH concentrations on viral mRNA cap-methylating enzymes will be investigated. Replication of human Cytomegalovirus in cultured fibroblasts will be monitored by the use of GFP labeled recombinant virus. We will be able to give answers, whether viral replication is affected by SAHH deficiency, because of irregular methylation processes. This could lead to new insights for Genetics mechanisms and necessary cellular factors, which are driving viral replication. Imprinting analysis will be performed by the bisulfite modification of DNA and subsequent PCR. Resulting PCR products are either analyzed by DNA sequencing or restriction digestion. The methylation status of the DNA segment is then determined by comparing the bisulfite treated DNA and untreated DNA. Proteomics will be monitoring changes at subcellular level such as posttranslational modification of the proteome with focus on biological methylation. Accordingly, our established model system based on cultured fibroblasts of patients allows comparison of DNA, RNA and protein modifications of cells cultured under different growth conditions as mentioned above for the genomics part. Two-dimensional (2-D) gelelectrophoresis and subsequent mass spectrometry is used to detect proteins with altered methylation profiles. Accordingly, protein extracts of cultured fibroblasts from a SAHH deficient patient, which have been grown at different temperatures will be compared and screened for differences in the proteome. Thus our goal will be the identification of differences in quantity of methylation sites between permissive and restrictive growth conditions using heavy methyl SILAC (stable isotope labeling by amino acids in cell culture). Namely, radioactively labeled methyl groups differ in their molecular weight if compared with nonradioactive methyl groups, which can be resolved through mass spectrometry. Detection of alteration by either SILAC or mass spectrometry indicates, that altered proteins are functionally connected through common pathways. Bioinformatics will thus lead to the uncovering of possibly unknown pathways of cellular processes involved in biological methylations. Further, identification of proteins with altered methylation will allow conclusions about the activity of enzymes involved in methylation processes such as methyltransferases. New emerging technologies such as proteome microarrays will be used to screen for proteins, which have lost their antigenicity because of loss of post-translational modification such as methyl groups. Also, we will be using classical western blot detection techniques with methylation-sensitive antibodies, which recognise methyl groups on the protein surface. Newly identified proteins with altered methylation profiles will be cloned using recombinant DNA technology and functionally analysed. We expect to identify yet unknown methyl acceptors, i.e. substrates of methyltransferases, which are involved in the complex pathogenesis of SAHH deficiency in human. Institution/University Name of Institution/University Institute Rudjer Boskovic Number of Employees 700 Number of Researchers 300 Country Croatia Postal Adress Bijenicka 54 10000 Zagreb Immunology and Immunohaematology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name prof. Milan Taradi Contact Person Name prof. Milan Taradi Email [email protected] Function Professor of Physiology and Immunology Phone 38514566921 Fax 38514590207 Website web.mef.hr Research Team Objectives Main Fields Immunology and Immunohaematology Information Technology, Statistics, Documentation Biology Tumour immunology Experimental allergic encephalomyelitis in rats E-learning Partners/Interests researcher Tumour immunology Immunology and Immunohaematology Institution/University Name of Institution/University University of Zagreb, Faculty of Medicine Number of Employees 800 Number of Researchers 500 Country Croatia Postal Adress Šalata 3 10000 Zagreb Immunology and Immunohaematology Research Team Research Team Name Individual Researcher No Research Team Leader Name MD, PHD Gordana Leposavic Research Team Members Team Member 0 BSc. Nataša Kuštrimović [[email protected]] Team Member 1 BSc. Katarina Mitić [[email protected]] Team Member 2 MSc. Ana Rakin [[email protected]] Team Member 3 BSc. Milica Perišić [[email protected]] Team Member 4 BSc. Ivan Pilipović [[email protected]] Team Member 5 MD Katarina Radojević [[email protected]] Team Member 6 PhD Nevena Arsenović-Ranin [[email protected]] Team Member 7 MD Vesna Kovačević-Jovanović [[email protected]] Team Member 8 PhD Mileva Mićić [[email protected]] Team Member 9 PhD Stanislava Stanojević [[email protected]] Team Member 10 PhD Duško Kosec [[email protected]] Team Member 11 PhD Bosiljka Plećaš-Solarović [[email protected]] Team Member 12 PhD Vesna Vujuć [[email protected]] Team Member 13 PhD Mirjana Dimitrijević [[email protected]] Research Team Projects Project Name Neuroendocrine immunomodulation: roles for the sympathoadrenomedullary system nomedullary system Project Leader Professor of Pathological Physiology Gordana Leposavic [[email protected]] Project Funding Agency Ministry of Science Republic of Serbia Project Budget 20000 € Project Start Date 2006-01-01 Project End Date 2010-01-01 Project Partners Immunology Research Center “Branislav Jankovic”, Institute of Immunology and Virology, Belgrade, Serbia Department of Medical Chemistry, School of Medicine, University Belgrade, Belgrade, Serbia Project Summary The sympatho-adrenomedullary (SA) system is thought to play an important part in the modulation of immune functions, particularly in aging individuals and conditions of stress. This project aims to enlighten the molecular and cellular mechanisms by which catecholamines (CAs) and neuropeptide Y (NPY, a co-transmitter in noradrenergic sympathetic nervous fibers) contribute to:1) the maintenance of immune homeostasis, and 2) the development of age- and stress-related alterations in the immune functions. The investigations will be focused on role for CAs and NPY in modulation of: a) T-cell development/ functions and b) macrophage activity in young, adult and aged rats. The study will encompass pharmacological manipulations of CA action in vivo and well-defined models of chronic stress. Changes in SA - immune communication during ageing and in models of chronic stress will be assessed by analyzing the concentrations of CA and NPY in blood and lymphoid organs/ immune cells, and the expression of their receptors on immune cells. To examine the direct effects of CAs, alone and in combination with NPY, on the target cells, agonists and antagonists of adrenoceptors (ARs) and/ or receptors for NPY will be used in thymus organ and lymphocyte/ macrophage cell cultures. The investigations will be carried out in the absence and presence of glucocorticoid (GC) action to address the significance of GCs in the effects of CAs and NPY on immune cells in vivo and in vitro. Contact Person Name MD, PHD Gordana Leposavic Email [email protected] Immunology and Immunohaematology Function Professor of Pathophysiology Phone +381 11 467 465 Fax +381 11 467 465 Website www.pharmacy.bg.ac.yu Research Team Objectives Main Fields Immunology and Immunohaematology Pathology Pharmacology Neuroendocrine-immune system interactions, T-cell differentiation/ maturation, macrophage/ neutrophil functions, inflammation, mechanisms of autoimmunity, development and aging of the immune system Partners/Interests researcher Immunology and Immunohaematology Pathology Pharmacology We are looking for a partner with experience in: a) in studies of the thymocyte selection and maturation, b) establishing various models of autoimmune diseases c) molecular techniques that will allow to define the impact of catecholamines / NPY on transcription and protein expression of multiple, immunologically relevant genes. I Catecholamines and thymocyte selection/maturation: ad 1. As we have shown that long-lasting beta-adrenoceptor (AR) blockade in rats affects development of both conventional and regulatory T cells leading to an intrathymic overrepresentation of the most mature single positive (CD4+8- and CD4-8+) TCRalpha/betahigh cells and CD4+25+ T regulatory cells (Mol. Cell. Biochem., 285:87-99, 2006), most likely, by influencing the thymocyte selection (possibly via action on Thy-1 surface expression), we are interested in continuing investigations of relationship between the effects of catecholamine (CA) and TCR ligand binding in T-cell selection and maturation. ad 2. Having in mind age-associated changes in the T-cell development, particularly those related to a pronounced decrease in the thymocyte Thy-1 surface density that we have observed in rats (Exp. Gerontol.41:574-589, 2006), on the one hand, and those in the sympathetic innervation of the rats thymus, on the other hand, we would like to undertake further studies on relationship between the effects of CA and TCR ligand binding in T-cell selection and maturation during the immune system ageing. ad 3. Since we have observed that intrathymic CA concentration is substantially influenced by gonadal steroid hormones (Neuroimmunomodulation, 7: 59-67, 2000, and our unpublished results), we are planning to examine relationship among the effects of CA and TCR ligand binding in T-cell selection and maturation in respect to sexual dimorphism, i.e. gonadal hormone presence. II Catecholamines in pathogenesis of autoimmune diseases: As we have demonstrated that long-lasting beta-AR blockade causes profound changes in susceptibility of DA rats to the induction of EAE, as well as in the clinical course of disease (Immunol. Letters, 73: 221, 2000), we are interested in undertaking a study to define the cellular and molecular targets underlining CA role in pathogenesis of autoimmune diseases. III NPY and catecholamines in modulation of macrophage functions: ad 1. In a view of our data showing that CAs and NPY, a sympathetic co-transmitter, modulate several functions of macrophages (Regul. Pept. 2005;124:163-72), we would be interested in studying the molecular mechanisms underlining these effects along with potential interaction between ARs and Y receptor subtypes in sympathetic control of macrophage activities. ad 2. We have also shown Y receptor subtype specific NPY modulation of inflammation and macrophage functions, as well as ageassociated alterations in Y1 receptor signaling (Exp. Gerontol. 2006; in press). As atherosclerosis is widely prevalent in ageing population, and as monocyte-derived macrophages are involved in pathogenesis of this disease, we would like to carry on further studies on putative contribution of an altered NPY signaling to the atherogenesis by analysis the effects of NPY on the expression of various immunologically relevant genes (e.g. pro-inflammatory cytokines) by macrophages. Institution/University Name of Institution/University Faculty of Pharmacy Number of Employees 200 Number of Researchers 110 Country Serbia and Montenegro Postal Adress Vojvode Stepe 450 11152 Belgrade Immunology and Immunohaematology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD PhD Dusan Popadic Research Team Members Team Member 0 MD PhD Dusan Popadic Contact Person Name Dusan Popadic Email [email protected] Function Associate professor Phone +381 11 2657 258 Fax +381 11 2657 258 Website www.med.bg.ac.yu Research Team Objectives Main Fields Immunology and Immunohaematology Neurology Autoimmune/Inflammatory diseases; Multiple sclerosis; Experimental allergic encephalomyelitis; Psoriasis; Cell culture; Flow-cytometry; Gene expression; Real-Time RT PCR Partners/Interests researcher industrial partner Immunology and Immunohaematology Neurology My partner should have similar research or commercial interest and background in manufacturing of vitamin A and D and polyunsaturated fatty acids compounds or experiance in treatment of inflammatory diseases with the available medicaments formulated on the analogs of vitamin A and D or polyunsaturated fatty acids. To test synthethic analogs of vitamin A and D and polyunsaturated fatty acids on lymphocyte and keratinocyte biology in terms of potential ability of those substances to modulate natural course of diseases such are Multiple sclerosis and Psoriasis vulgaris. Institution/University Name of Institution/University Institute of Microbiology and Immunology Number of Employees 45 Number of Researchers 25 Country Serbia and Montenegro Postal Adress Dr Subotica 1 11000 Belgrade Immunology and Immunohaematology Research Team Research Team Name Biological effect of dental materials Individual Researcher No Research Team Leader Name Assistant professor Sonja Pezelj-Ribaric Research Team Members Team Member 0 assistant Domagoj Maričić [[email protected]] Team Member 1 assistant Vlatka Mikić [[email protected]] Team Member 2 assistant Davor Kuiš [[email protected]] Team Member 3 assistant Vladimir Ahel [[email protected]] Team Member 4 assistant Silvio Ferreri [[email protected]] Team Member 5 assistant Irena Glažar [[email protected]] Team Member 6 assistant Hrvoje Gazdik [[email protected]] Team Member 7 assistant Jelena Horvat [[email protected]] Team Member 8 asisstant professor Renata Gržić [[email protected]] Team Member 9 assistant professor Ivana Brekalo Pršo [[email protected]] Contact Person Name Assistant professor Sonja Pezelj-Ribaric Email [email protected] Function Head of department Phone ++38551633455 Fax ++38551345655 Website medri.hr Research Team Objectives Main Fields Immunology and Immunohaematology Clinical microbiology Dentristry Null-hypothesis is that there will be no difference between expected and obtained results during biocompatibility, immunohistochemical, allergological, microbiological and epidemiological analyses. The problem with composites, prosthodontic and restorative metals, drugs used in treatment of various pathological changes of oral mucosa, as well as usage of various preparations which can change their state of matter is that they can act as toxic or allergenic. Therefore the project wishes to answer: in what way does the tissue respond to new dental materials in in vitro and in vivo conditions. The assumption is that the raw materials used in production of different purpose dental materials have already been tested during production stage, and have been declared as biocompatible, but chemical properties of raw materials as well as newly-formed compounds can be altered. This way, and during tissue interactions, biocompatibility can be decreased. Therefore it is very important to run permanent tests on preparations regarding their degree of conversion and duration of contact with living tissue. The assumption is that results will facilitate choice of dental materials in clinical work. Lack of epidemiological data on condition of oral mucosa, especially in population of Rijeka and specifically older population (retired persons) is imposed as one of chief scientific and clinical problems. We can assume further that epidemiological analyses of oral health condition and all the changes on oral mucosa will contribute to prevention and more efficient planning of their clinical recovery. The occurrence of Candida species and subsequent pathological changes in relation to prosthodontic treatment (especially removable prostheses) and treatment procedures of oncologic patients are the focus of interest of many scientific investigations. Using microbiological tests, and by isolation and identification of Candida species in relation to applied materials and therapy, we can assume that better and faster cure will be enabled, thereby shortening the course of disease. Proving the adherence ability, macrophage phagocitosis and microbicidal activity in relation to the tested dental materials are of primary importance for tissue response. Determination of the levels of pro-inflammatory cytokines using immunological tests can affect the choice of therapeutic means. Partners/Interests researcher Microbiology Immunology and Immunohaematology Pathology Dentristry Specialist in clinical microbiology Specialistin oral pathology Biocompatibility tests using the analysis of tissue reaction after implantation of new materials for root canal obturation: epoxy-resins, polyketons, silicones, composite resins, calcium-hydroxide and materials for retrograde obturation: MTA, IRM, Super EBA applied into subcutaneous and bone tissue of experimental animals. For experimental animals, Wistar rats will be used, of 180 -230 g weight (5 rats) which will be held at the vivarium of Department of pharmacology, Medical Faculty, University of Rijeka. Rats will be kept in Plexiglas cages in groups of 6-8 on sawdust which is dusted and autoclaved, and is changed regularly. Temperature of the filtered air, which is under positive pressure, is 22 ± 2ºC, humidity 55- 60% and illumination of 300 Lux. Rats will be given water ad libitum and fed using standardized palettes specially designed for laboratory rats. Rats will be occasionally controlled for appearance of certain pathogens. Before initiation of the research, rats will be anesthetized using halothane. Anesthesia will be implemented according to the instructions of the existing immunology protocol (Care and Handling of Laboratory Animals). Afterwards we will implant the materials into the subcutaneous tissue and animals will be sacrificed using CO2 as regulated by the Law on Animal Well-being and international standards of the EU: EC Directive 86/609/EEC after 7 and 30 days, respectively. Histological evaluation will be performed by analyzing the number, type and location of inflammatory cells. Reaction of bone tissue will be evaluated using silicone tubes which will be implanted into the rats' tibiae. Rats will be sacrificed after 60 days after the abovementioned protocol, after which we will perform histological and histomorphometrical analyses. The expected duration of research is three years. b) Influence of the following materials to adherence ability, phagocitosis and microbicidal activity of macrophages will be determined: epoxy-resins, polyketons, silicones, composite resins, calcium-hydroxide, and materials for retrograde filling: MTA, IRM, and Super EBA. Influence of dental materials on macrophages will be tested in in vivo conditions. As a model, female mice will be used, aged 8-12 weeks. Laboratory mice will be put in central vivarium of Medical Faculty, University in Rijeka, after standards set by European Union. Institution/University Name of Institution/University Medical faculty Number of Employees 350 Number of Researchers 100 Country Croatia Postal Adress Brace Brancheta 20 51000 Rijeka Immunology and Immunohaematology Research Team Research Team Name Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia Individual Researcher No Research Team Leader Name Prof. Dr. Mirko Spiroski Research Team Members Team Member 0 MD Jordan Petrov [[email protected]] Team Member 1 Molecular biologist Olgica Sibinovska [[email protected]] Team Member 2 MD Eli Spiroska [[email protected]] Team Member 3 MD Slavica Hristomanova [[email protected]] Team Member 4 Biotech Olivija Efinska-Mladenovska [[email protected]] Team Member 5 MD Ana Strezova [[email protected]] Team Member 6 MD, MSc Aleksandar Petlichkovski [[email protected]] Team Member 7 MD, MSc Dejan Trajkov [[email protected]] Research Team Projects Project Name Ambiguities Resolution of HLA Genotypes in Macedonian Population Project Leader Prof. Dr. Mirko Spiroski [[email protected]] Project Funding Agency INTERNATIONAL CENTRE FOR GENETIC ENGINEERING Project Budget 36000 € Project Start Date 2004-01-01 Project End Date 2006-12-31 Project Partners Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Macedonian Donor Registry and Bone Marrow Transplantation Dimitar Efremov, M.D., Ph.D. Associate Professor of Medicine and Group Leader Clinic for Haematology, Faculty of Medicine, Vodnjanska 17, 1109 Skopje, Macedonia. present address: CNR Campus "Adriano Buzzati-Traverso" Via E. Ramarini 32 I-00016 Monterotondo Scalo (Rome), Italy tel: +39-3337199691 fax: +39-06-90091260 E-mail: [email protected] Project Summary A total of 580 persons from the Republic of Macedonia divided in the four groups will be DNA-HLA genotyped: 1. Donors (unrelated healthy persons) of the Macedonian Donor Registry (250); 2. Patients for bone marrow transplantation and related potential donors (brothers, sisters, and parents) (50); 3. Patients with rheumatoid arthritis, tuberculosis, cardiomyopaties and other diseases (150); and 4. Ambiguity resolution of the genotypes (130). Genomic DNA will be isolated from peripheral blood of individuals according to standard phenol/chlorophorm procedure. Class I HLA genes (A, B, and C)will be typed by Reverse Line Strip Typing (RLS); Class II HLA gene (DRB!) will be typed by Sequence Based Typing (SBT). Three different strategies will be used for ambiguities resolution: 1) Comparison of the genotype with the genotypes of the family members; 2) Use of group specific primers (GSAP); and 3) Use of sequence specific primers (SSP) for amplification of specific allels. Data of the DNA-HLA typing will be stored in Excel files specified by the 13th International Histocompatibility Working Group. Software for Population Genetic data Analysis (Arlequin, ver. 2000) will be used for statistical analysis of allels, haplotypes, Hardy-Weinberg equilibrium, Pairwise linkage disequilibrium by Slatkin, Ewens-Watterson tests of selective neutrality, Chakraborty's test of selective neutrality and other indices. Project objectives are: 1. Creation of Macedonian Donor Registry (MDR) and connection with the European and World Marrow Donor Registries. 2. HLA typing of unrelated healthy persons using methods already established in our laboratory: RLS for Class I HLA-A, -B, and -C typing, and SBT for Class II HLA-DRB1 typing. 3. HLA typing of patients for bone marrow transplantation and related potential donors (brothers, sisters, and parents). 4. HLA typing of samples from the patients with rheumatiod arthritis, tuberculosis, cardiomyopathies, and other diseases associated with HLA allels. 5. Evaluation of allele and genotype ambiguities for Class I and Class II typings and definition of strategy for their resolution. 6. Introduction and establishment of Immunology and Immunohaematology sequencing based methods for typing of Class I HLA -A, -B, and -C loci. 7. Introduction and establishment of method that uses sequence specific primers (SSP) for resolving the ambiguous results for Class II typing. Project Website www.immunology.edu.mk Project Name Molecular Analysis of Cytokine Gene Polymorphisms in Republic of Macedonia Project Leader Prof. Dr. Mirko Spiroski [[email protected]] Project Funding Agency Ministry of Education and Sciences, Macedonia Project Budget 15000 € Project Start Date 2006-07-01 Project End Date 2009-06-30 Project Partners Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Special Education and Rehabilitation, Faculty of Philosophy, University "Ss. Kiril and Metodij", Skopje, Republic of Macedonia; Dental Clinical Center, Department of Oral Pathology and Periodontology, Faculty of Stomatology, University "Ss. Kiril and Metodij", Skopje, Republic of Macedonia; Clinic for Pediatrics, Clinical Center, Faculty of Medicine, University "Ss. Kiril and Metodija, Skopje, Republic of Macedonia. Project Summary Cytokine gene polymorphism of gamma-interferon (IFNg); interleukin (IL) 1 alpha (IL-1a); IL-1 beta (IL-1b); IL-1 receptor (IL-1R); IL-1R antagonist (IL-1RA); IL-2; IL-4; IL-4 receptor alpha (IL-4Ra); IL-6; IL-10; IL-12B; TGF beta 1 (TGF-b1); and TNF alpha (TNF-a) will be determined in healthy population leaving in the Republic of Macedonia (Macedonians, Albanians, Roma); patients with pulmonary tuberculosis; patients with parodontopathia; patients with atopic dermatitis; patients with reumatoid arthritis; patients with bronchial asthma; patients with chronic obstructive bronchitis; and patients with dilated cardiomyopathy. Association of cytokine gene polymorphism with the above diseases will be analyzed. Project Website www.immunology.edu.mk Project Name Blood Homocysteine Level and Prevalence of C677T Mutation of Enzyme Methylentetrahydropholate Reductase (MTHFR) as a Risk Factors for Blood Vessel Diseases. Project Leader Prof. Dr. Slobodanka Dzhekova-Stojkova [[email protected]] Project Funding Agency Ministry of Education and Scineces, Macedonia Project Budget 10000 € Project Start Date 2003-07-01 Project End Date 2006-06-30 Project Partners Institute of Medical and Experimental Biochemistry, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Transfuziology, Skopje, Republic of Macedonia. Project Summary Homocysteine (Hcy) is natural amino acid that has attained greater importance in the clinical investigations. Epidemiological studies performed among general population have suggested association between the increased level of circulatory Hcy and premature coronary, cerebral and peripheral atherosclerosis and venous thromboembolism. The aim of this investigation is introduction and eventual modification of a method for Hcy determination as well as determination of the reference values for the population in R. Macedonia. The intention is to determine the concentration of Hcy in patients with coronary artery disease (CAD) and deep venous thrombosis (DVT); to examine the prevalence of C677T mutation of enzyme methylentetrahydropholate reductase (MTHFR) and to analyze the correlation of MTHFR C677T genotype with the Hcy values in serum of both healthy population and patients with the concerned diseases. By accomplishing the outlined aims of the investigation, for the first time in our country we expect to introduce a method for determination of Hcy concentration in serum. We expect to obtain significantly higher values for Hcy in the groups of Immunology and Immunohaematology patients with CAD and DVT in comparison with the healthy population. By examining the gene of the enzyme MTHFR, we assume to get information on the prevalence of its C677T mutation in healthy population and in the examined diseases. In addition to this, we anticipate to have insight in the correlation between the normal and mutated allele and Hcy level in the serum of both healthy subjects and examined patients. Using combined vitamin therapy (B6, B12 and folate) reduction of Hcy concentration could be provoked, thus its determination could be one component in preventing vascular diseases. Project Website www.immunology.edu.mk/ Project Name HLA-DNA Investigations in the Families with Autism in the Republic of Macedonia Project Leader Assist. Prof. Dragoslav Kopachev [[email protected]] Project Funding Agency Ministry of Education and Science, Macedonia Project Budget 10000 € Project Start Date 2001-07-01 Project End Date 2004-06-30 Project Partners Institute of Special Education and Rehabilitation, Faculty of Philosophy, University "Ss. Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia Project Summary The frequencies of HLA-DNA alleles will be analyzed at the children with autism, their parents, and their siblings in the Republic of Macedonia who are diagnosed with ICD-10 and DSM-IV criteria. The research includes 31 autistic persons and 31 health persons. Families who have autistic children will be registered in special forms and will be stored in data base. The frequencies of HLA-DNA A, B, C, and D alleles will be determine with high resolutive molecular biologic techniques such as SSOP (Sequence Specific Oligonucleotide Probes), RLS (Reverse Line Strip), and/or SBT (Sequencing-based Typing). For establishing the differences in frequencies of HLA-DNA alleles between the health and autistic children, also between parents and autistic children, and between these children and their siblings will be made a statistic analysis. The results will be presented and published. Project Website http://def.fzf.ukim.edu.mk/ Project Name Serum Immunoglobulins and Specific Food Allergens in the Persons with Autism in the Republic of Macedonia Project Leader Prof. Ljupcho Ajdinski [[email protected]] Project Funding Agency Ministry of Education and Science, Macedonia Project Budget 10000 € Project Start Date 2000-07-01 Project End Date 2003-06-30 Project Partners Institute of Special Education and Rehabilitation, Faculty of Philosophy, University "Ss. Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Immunobiology and Human Genetics, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia. Project Summary Autism is wide continuum of connected cognitive and neurobehavioral disorders, including three features: impairments in socialization, impairments in verbal and nonverbal communication, and restrictive and repetitive patterns of behavior. From 35 persons blood was taken, such as 22 their brothers/sisters, 27 mothers, and 23 fathers in the period between the July 2000 to the June 2003 year. Ten milliliters of venous blood was drawn from each donor by the standard venipuncture in vacutaners with EDTA (K3). At the time of blood drawing, none of autistic children were receiving any medication or antipsychotic drug. Plasma samples were separated by centrifugation and stored at – 200C till the determination. Serum immunoglobulin classes and subclasses are determined immunonephelometric by automated Dade-Behring Nephelometer Analyzer. Serum specific food allergens are determined by Pharmacia UniCAP 100 in vitro automated solid phase immunofluorescence. Plasma concentration of IgG4 subclass immunoglobulin is significantly higher in persons with autism (p < 0.02). Statistically significant higher plasma concentration of IgG antibodies against alfa-lactalbumin, beta-lactoglobulin and casein is found in autistic persons compared to their Immunology and Immunohaematology parents (p < 0.001). The concentration of IgG gliadin antibodies in autistic persons was found to be higher compared to their mothers and fathers which is statistically significant (p < 0.04). Plasma concentration of specific allergic IgA antibodies against beta-lactoglobulin in persons with autism is significantly higher compared to brothers and sisters (p < 0.05). The level of casein IgA antibodies in autistic group was significantly higher compared with those of their mothers and fathers (p < 0.01) and brothers/sisters (p < 0.05). The level of casein and beta-lactoglobulin specific allergic IgE antibodies in the serum of autistic patients was significantly higher compared with those of their brothers/sisters and their parents (p < 0.04). The level of total IgE antibodies was statistically significant higher in autistic persons compared to their mothers (p<0.04) and their brothers/sisters (p < 0.02). The established immunological and allergological disturbances give more opportunities for realization of immunodiagnostic, immunotherapy, and starting a diet without allergic products from the food in Republic of Macedonia. Index terms: autism, specific allergic antibodies, immunoglobullins, Republic of Macedonia. Project Website http://def.fzf.ukim.edu.mk/ Project Name Determination of Lp(a), HDL, and LDL subclasses in children population Project Leader Prof. Dr. Bojana Todorova [[email protected] ] Project Funding Agency Ministry of Education and Science, Macedonia Project Budget 10000 € Project Start Date 2000-07-01 Project End Date 2003-06-30 Project Partners Institute of Medical and Experimental Biochemistry, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Clinic for Childrens Disease, Clinical Center-Skopje, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia. Project Summary Lipoprotein (a) [Lp(a)] is a plasma particle, similar in size and composition to the LDL, composed of Apo(a) ¡Vprotein unique for Lp(a) and ApoB-100 linked with one or more disulfide bonds. High plasma Lp(a) concentrations as well as low molecular weight Apo(a) isoforms are thought to be an independent risk factor for atherosclerosis development. Low density lipoprotein (LDL) and high density lipoprotein (HDL) are heterogeneous classes composed of several subclasses which differ in density, size and composition, and this heterogeneity is thought to be genetically influenced. Small LDL particles are thought to be more atherogenic than larger LDL subclasses, and their frequency may depend on plasma lipid and apoprotein levels. The development of atherosclerosis is also afected by specific pattern of plasma HDL subclasses. The aim of this project was to determine Apo(a) isoforms and particle size distribution of LDL and HDL subclasses by gradient gel electrophoresis and immunoblotting technique in both healthy children and children with diabetes mellitus and renal diseases. In healthy children population in the Republic of Macedonia, the most frequently found were HMW isoforms (>S4, S4, S4S3,>S4S4) associated with low plasma Lp(a) concentrations. Molecular mass of the isoforms was in the range of 451-781kDa and the distribution of Lp(a) plasma concentration (mean „b SD: 11.95 „b 5.97 mg/dL) was shifted towards low concentration in most of the subjects (98%) having Lp(a) plasma concentration bellow the risk limit of 30 mg/dL. As expected, there was a statistically significant inverse correlation between Apo(a) isoform size and Lp(a) plasma level (r=-0.4257, p<0.001). Except statistically significant elevation in plasma Lp(a) concentration in children with renal diseases, we found no other differences in determined parameters in diabetic and children with renal diseases in comparison with healthy children. Analysis of LDL phenotype has shown that in a big percent of healthy children (89%) bigger LDL1 and LDL2 subclasses were dominant, that is, phenotype A, whereas 11% of the children belonging to phenotype B were characterized by the presence of small, atherogenic LDL3 and LDL4 subclasses. The distribution of HDL subclasses showed domination of bigger HDL2b and HDL2a subclasses in 94,5%, whereas only in 5,5% of the children small HDL3a and HDL3b subclasses were dominant. These results have revealed an antiatherogenic LDL and HDL subclass profile in healthy children in R. Macedonia. Although there were no differences in the plasma lipid profile in children with insulin dependent diabetes mellitus compared with healthy children, the frequency of phenotype B was increased (88,5%), and the mean LDL diameter was smaller (p<0,0001). These changes in LDL subclasses distribution were especially evident in children with renal diseases where even 95% belonged to atherogenic phenotype B. HDL subclasses distribution in both patient groups was also shifted towards smaller, atherogenic HDL subclasses. These findings confirm the fact that in children with diabetes mellitus and renal diseases Immunology and Immunohaematology the risk for atherosclerosis development is increased. Determination of LDL and HDL subclasses distribution and Apo(a) isoforms as well as plasma Lp(a) levels in healthy children population and in patients, may help in preventing and reduceing the risk for atherosclerosis development. Project Website Project Name Plasma LDL and HDL lipoproteins and their phenotypes Project Leader Assist. prof. Sonja Alabakovska [[email protected] ] Project Funding Agency Ministry for Education and Science, Macedonia Project Budget 15000 € Project Start Date 2006-07-01 Project End Date 2009-06-30 Project Partners Institute of Medical and Experimental Biochemistry, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Institute of Immunobiology and Human Genetics (IIBHG), Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia; Clinic for Childrens Disease, Clinical Center-Skopje, Faculty of Medicine, University "Ss Kiril and Metodij", Skopje, Republic of Macedonia. Project Summary Low density lipoprotein particles (LDL) and high density lipoprotein particles (HDL) are heterogeneous fractions composed of several subclasses different in density, size and chemical composition. The lipoprotein profile, characterized by the domination of LDL-1 and LDL-2 subclasses is called LDL phenotype A and the lipoprotein profile characterized by the domination of LDL-3 and LDL-4 subclasses is called phenotype B. Small LDL particles are thought to be more atherogenic than larger LDL subclasses and increase of the concentration of sLDL particles (phenotype B) is associated with a 3 times greater risk of heart attack. The development of atherosclerosiss is also afeceted by a specific pattern of plasma HDL particles subclasses. Small HDL3a, HDL3b and HDL3c subclasses which accept cholesterol from peripherial cells less efficient, increases the risk of development atherosclerosis. The data from several studies, as well as our own results proof the role of LDL and HDL subclasses in the development of atherosclerosis. For further investigartion of the role of LDL and HDl in the development of CAD we would like to anlyse the association between progression of the coronary artery lesion (rate of arterial stenosis) and the concnetration of small lipoprotein subclasses. Althdough it is considered that lipoprotein distribution is geneticaly determined, rescently, there are more evidence showing the importance of the non-genetic factors such as: high concentration of plasma triglycerides, low concnetration of HDL cholesterol, diet, age and the hormonal status of the females. It is well known fact that the risk for atherosclerosis development is higher in males than in females. Our results as well as literature data show that LDL lipoprotein profile type B is more frequently found in males than in females. But, rescent investigations sugesst that this picture is changing in the period of postmenopause in females when plasma concentration of triglyceride and LDL choletesterol are increased, HDL cholesterol is decresed and lipoprotein subclass distribution changes towards smaller atherogenic subclasses. Therefore, lately the attention of the investigators is focused on the effect of hormonal replacement therapy with estrogens in postmenopausal women on the lipid profile and especially on LDL and HDL subclass distribution. Therefore, second challenge in this project would be following the effect of the hormeone replacement therapy with estorgens which may present an excellent model for evaluation of the antiatherogenic influence of the estrogens on the lipid methabolism. The aim of this project is to determine particle size distribution of LDL and HDL subclasses phenotype by gradient gel electrophoresis in patients with coronary artery disease and to follow up the relationship between lipoprotein subclasses and the rate of coronary artery stenosis determined by selective coronarygraphy as well as the carotid artery intima-media thickness determined by carotid ultrasonography . Also, phenotypization of the LDL and HDL subclass profile will be determined in the postmenopausal women before and after the hormpne replacement therapy, folowing the effect of the therapy on the lipoprotein profile. In both groups of patients correlation will be performed between lipoprotein phenotype and other lipid and apoprotein parameters determined. We expect that the results from this study will point the necesserity of the LDL and HDL subclass distribution determination in each patient. It will help in the diagnose of the subjects with increased risk of appearance and progression of the atherosclerotic changes of the blood vesels as well as for determining the respective hipolipidemic therapy and hormone replacement therapy as an prevention. Project Website Immunology and Immunohaematology Contact Person Name Prof. Dr. Mirko Spiroski Email [email protected] Function Director, professor of immunology and human genetics Phone 389 2 3110556 Fax 389 2 3110558 Website immunology.edu.mk/ Research Team Objectives Main Fields Immunology and Immunohaematology Genetics Public health services - Immunodiagnostcs: Acute phase proteins, Ig classes, Ig subclasses, total and specific IgE (allergology), autoantibodies, cytokines, flow cytometry. - Immunogenetics: HLA-DNA genotyping (HLA-A, -B, -C, -DRB1, -DQ), cytokine gen polymorphisms, killer cell immunoglobulin-like receptors (KIRs) polymorphism. - Human Genetics: cardiovascular disease (CVD) mutations (FV G1691A (Leiden), FV H1299R (R2), Prothrombin G20210A, Factor XIII V34L, ¥â-Fibrinogen -455 G-A, PAI-1 4G/5G, GPIIIa L33P (HPA-1), MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q, Apo E2/E3/E4), ALAD, ©¬-Globin, Haemochromatosis, FMF, Gaucher Disease, Sugar Intolerance. Partners/Interests researcher Immunology and Immunohaematology Genetics Public health services Immunology, molecular biology, immunogenetics, human genetics Institution/University Name of Institution/University Institute of Immunobiology and Human Genetics (IIBHG) Number of Employees 10 Number of Researchers 7 Country Macedonia Postal Adress 50 Divizija No 6, PO Box 60 6 1109 Skopje Immunology and Immunohaematology Research Team Research Team Name Interferons Individual Researcher No Research Team Leader Name Mr., MD Ales Goropevšek Research Team Members Team Member 0 Mr. MD, PhD Ivan Krajnc [] Team Member 1 Mrs. PhD Avrelija Cencic [] Contact Person Name Mr., MD Ales Goropevšek Email [email protected] Function researcher Phone + 386 2 321 10 00 Fax +386 2 331 23 93 Website www.sb-mb.si Research Team Objectives Main Fields Immunology and Immunohaematology Interferons Partners/Interests researcher industrial partner Suitable Immunology and Immunohaematology 1. INTERFERONS AND CYTOKINES IN CHRONIC INFLAMMATORY DISEASES Almost all current therapeutic concepts in chronic inflammatory diseases are based on the systemic suppression of immune functions and are not curative. Identification of cytokines TNF and IFN-α as major factors in the pathogenesis of diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) represent a substantial improvement in understanding of autoimmune diseases. However, knowledge of the molecular mechanisms underlying and regulating the production of type I interferons is still lacking . Professional type I interferon-producing cells also known as plasmacytoid dendritic cell precursors (pDCs) represent unique subpopulation of dendritic cells. Together with other DCs they play a master role in the control of immunity and in host-pathogen interactions. The study of DCs and their subpopulations was limited by the absence of specific markers and their low frequency in human and mouse tissues and blood . Because pDCs undergo rapid spontaneous apoptosis in culture in vitro studies are also very limited. We succeeded in establishment of a first novel pDC cell line, which will give us oportunity to study pDCs in vitro. Phospho-proteomic immune analysis by flow cytometry will give us biochemical access to rare cell subsets such as those from clinically derived samples or populations that comprise too few in numbers for conventional biochemical analysis. Studies of multiple activated signaling pathways (in complex populations of cells) at the single-cell level will be done using various (TLR) agonists and kinase inhibitors. This will give us insight into mechanisms of cytokine (IFN-alpha) induction, action and its downstream mediators. Single-cell signal network analysis can also be used to stratify patients and may be useful for understanding mechanisms of disease progression, treatment resistance, and development of diagnostic indicators. Understanding (p)DC biology holds future promise for developing cures for autoimmune diseases, infectious diseases, and cancer. Since the mid-1990s, an immense number of kinase inhibitors has been characterised in vitro, and to date several compounds have been advanced into clinical trials. Small molecular, orally active anti-cytokine agents, which target specific pathways of proinflammatory cytokines, would offer an attractive alternative also to anti-cytokine biologicals. Institution/University Name of Institution/University General Hospital Maribor Number of Employees 2400 Number of Researchers 33 Country Slovenia Postal Adress Ljubljanska 5 2000 Maribor Immunology and Immunohaematology Research Team Research Team Name Laboratory for Imunnoneuroendocrine network research Medical faculty Belgrade & Medical faculty Foca University of East Sarajevo Individual Researcher No Research Team Leader Name M.D., Ph.D., physiologist Vojislav Pantic Research Team Members Team Member 0 assistant Dejan Bokonjic [] Team Member 1 assist professor Snezana Medenica [] Team Member 2 assist professor Milan Kulic [] Team Member 3 professor, hystolog Senka Pantic [] Team Member 4 professor, physiolog Vojislav Pantic [] Team Member 5 assistant Milica Kunarac [] Team Member 6 assistant Starovic Suncica [] Team Member 7 assist professor Sinisa Ristic [] Research Team Projects Project Name Immunotoxicology of tobacco smoking Project Leader assistant professor Sinisa Ristic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2007-01-01 Project End Date 2010-01-01 Project Partners Project Summary role of neuroendocrine system in immunotoxicology of tobacco smoking Project Website role of vegetative nervous system in immunoregulation Project Name full professor vojislav pantic [[email protected]] Project Leader Project Funding Agency € Project Budget 0001-01-01 Project Start Date 0001-01-01 Project End Date Project Partners Project Summary Project Website Contact Person Name M.D., Ph.D., physiologist, radiologist sinisa ristic Email [email protected] Function assistant profesor Phone 00 387 65 44 76 88 Fax 00 387 58 210 007 Website www.medfak.srbinje.net Research Team Objectives Main Fields Immunology and Immunohaematology Physiology Toxicology Immunology and Immunohaematology immunoneuroendocrine network research - role of vegetative nervous system and various hormones in regulation of immune response, immunotoxicology of tobacco smoking Partners/Interests researcher Toxicology Physiology Immunology and Immunohaematology basic researcher in biomedicina role of indirect mechanism (neuroendocrine system and their signal molecules) in immunotoxicology of tobacco smoking animal model, cell culture Institution/University Name of Institution/University Medical faculty Foca Number of Employees 150 Number of Researchers 20 Country Bosnia and Herzegovina Postal Adress Solunskih dobrovoljaca 1 73300 Foca Immunology and Immunohaematology Research Team Research Team Name Research group in Osteoimmunology/Hematology; Department of Physiology and Immunology/University of Zagreb School of Medicine/Zagreb/Croatia Individual Researcher Yes Research Team Leader Name MD, PhD Danka Grcevic Research Team Members Team Member 0 PhD student Vedran Velagic [[email protected]] Team Member 1 MD, PhD Zrinka Jajic [[email protected]] Team Member 2 PhD student Anita Lukic [[email protected]] Team Member 3 MD, PhD Danka Grcevic [[email protected]] Research Team Projects Project Name T- and B-lymphocytes in the regulation of bone metabolism Project Leader MD, PhD Danka Grcevic [[email protected]] Project Funding Agency Croatian Ministry of Science, Education Project Budget 50000 € Project Start Date 2002-07-01 Project End Date 2006-06-31 Project Partners Croatia/University of Zagreb School of Medicine/Department of Physiology and Immunology Project Summary In addition to their physical proximity, immune and bone systems are also functionally related. T- and B-lymphocytes produce cytokines and growth factors that may regulate bone cells and bone remodeling, directly or indirectly. Members of the tumor necrosis factor-related family of molecules are specifically important: receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL) and osteoprotegerin (OPG). Those molecules are essential regulators of the differentiation and function of both bone and immune cells. RANKL stimulates bone resorption after binding to activation receptor RANK, whereas OPG acts as decoy receptor, which blocks RANKL/RANK interaction. The aim of the proposed research is to investigate the role of T- and B-lymphocytes in bone metabolism. Since lymphocytes may secrete both osteoresorptive and osteoprotective cytokines, we hypothesized that changes in bone marrow lymphocyte populations would disturb the cytokine balance, and, therefore, affect the differentiation and function of bone cells. The investigation will be performed through several phases in vivo and in vitro, on the mouse model: 1. Bone cell differentiation will be followed after depletion of different lymphocyte populations with monoclonal antibodies, 2. Effect of activated lymphocytes will be studied in vivo on the inflammatory model (after administration of bacterial lipopolysaccharide) or after immunization with allogeneic cells, and in vitro after addition of activated lymphocytes in osteoblast or osteoclast bone marrow cell cultures, 3. Immunosuppressants cyclosporin A and glucocorticoids will be used in vivo and in vitro to investigate the effect of immunosuppression on the differentiation and function of bone cells. We expect that depletion, suppression or activation of lymphocyte populations will affect the bone remodeling, specifically through changes in RANKL/RANK/OPG system. Those effects will be assessed by the analysis of osteoclast and osteoblast differentiation, gene expression for regulatory molecules and phenotypic markers of bone marrow cells. The results of proposed investigation would add to the understanding of a number of pathological states that develop in bone microenvironment and affect bone metabolism, but not originated from bone cells. Some examples are posttransplantation osteoporosis, rheumatoid arthritis, osteomyelitis, periodontitis, certain immunodeficient disorders, chronic viral infections and hematopoietic malignancies. Project Website www.mzos.hr Project Name Molecular Interactions between Bone and Bone Marrow Project Leader MD, PhD Ana Marusic [[email protected]] Project Funding Agency Croatian Ministry of Science, Education Project Budget 75000 € Project Start Date 2002-07-01 Project End Date 2006-06-31 Immunology and Immunohaematology Project Partners Croatia/Zagreb University School of Medicine/Department of Anatomy Project Summary The project is dealing with the functional interactions between bone and bone marrow using different in vivo and in vitro models. Project Website www.mzos.hr Project Name Common progenitor of B-lymphocytes and osteoclasts Project Leader MD, PhD Vedran Katavic [[email protected]] Project Funding Agency Croatian Ministry of Science, Education Project Budget 30000 € Project Start Date 2002-07-01 Project End Date 2006-06-31 Project Partners Croatia/University of Zagreb School of Medicine/Department of Anatomy Project Summary The project is dealing with the common hematopoietic progenitor cells of B-lymphocytes and osteoclasts, particularly their characterization and regulatory mechanisms. Project Website www.mzos.hr Project Name Interactions Between Bone and the Immune System: A role for Fas-Mediated Apoptosis Project Leader MD, PhD Ana Marusic [[email protected]] Project Funding Agency The Wellcome Trust Collaborative Research Ini Project Budget 50000 € Project Start Date 2004-05-01 Project End Date 2006-04-30 Project Partners Ana Marusic/Croatia/University of Zagreb School of Medicine/Department of Anatomy; Collaboration with Prof. Peter Croucher, Sheffield University, UK Project Summary The project is dealing with the importance of the Fas ligand - Fas mediated apoptosis in the regulation of bone cell differentiation and survival. Project Website www.wellcome.ac.uk Contact Person Name MD, PhD Danka Grčević Email [email protected] Function Assistant Profesor Phone 385 1 4566 944 Fax 385 1 4590 222 Website mef.hr Research Team Objectives Main Fields Immunology and Immunohaematology Biology Osteoimunology, Bone biology, Immunohematology, Oncology Partners/Interests researcher Immunology and Immunohaematology Biology Research experience in the field of Osteoimmunology/Immunohematology/Oncology We propose a study within the novel field of osteoimmunology, with a specific interest in the functional interactions between immune and bone systems. The main hypothesis is that the disturbances, which mainly affect the immune system, cause the changes in the production of cytokines and growth factors by affected immune cells, with the consequence in the disturbed Immunology and Immunohaematology differentiation and functions of bone cells and bone metabolism. We expect that the disturbances originating mainly in lymphocytes will cause numerous changes in bone cell cultures in vitro an in the microenvironment of diseases in vivo. This hypothesis will be tested on several models – experimental mice that will enable us to use different in vivo models, cell lines that are suitable to study the contribution of certain cell populations and cytokines in carefully controlled and optimal in vitro conditions, and human samples to finally confirm the important role of the cytokine microenvironment in the pathogenesis of certain human diseases. Institution/University Name of Institution/University University of Zagreb School of Medicine Number of Employees 500 Number of Researchers 250 Country Croatia Postal Adress Šalata 3 10000 Zagreb Information Technology Research Team Research Team Name Image Processing Group Individual Researcher No Research Team Leader Name Prof. Dr. Sven Loncaric Contact Person Name Prof.dr. Sven Loncaric Email [email protected] Function Associate Professor of Electrical and Computer Engineering Phone +385-1-6129-891 Fax +385-1-6129-652 Website http://ipg.zesoi.fer.hr/loncaric Research Team Objectives Main Fields Information Technology, Statistics, Documentation Image Processing Group has expertise in developing methodology and computer programs for processing and quantitative analysis of two-dimensional and three-dimensional images and image sequences (video) obtained by various medical imaging techniques. Such methods can be applied to any medical image in order to enhance images for human viewing, or for analysis of anatomical or functional images. Applications are both in diagnostics and in interventions in medicine. Partners/Interests researcher industrial partner Information Technology, Statistics, Documentation We seek a medical partner who requires research and development of new methods for analysis of medical data, which can be in the form of signals, images, or videos. We seek medical partners requiring our expertise in development of computer-based medical image analysis methods. Institution/University Name of Institution/University University of Zagreb, Faculty of Electrical Engineering Number of Employees 250 Number of Researchers 200 Country Croatia Postal Adress Unska 3 10000 Zagreb Information Technology Research Team Research Team Name Informatics Individual Researcher No Research Team Leader Name Mr., PhD Dejan Dinevski Contact Person Name Mr., PhD Dejan Dinevski Email [email protected] Function Assistant Professor of Informatics Phone + 386 2 234 56 01 Fax + 386 2 234 56 00 Website http://www.mf.uni-mb.si/ang/main.htm Research Team Objectives Main Fields Information Technology, Statistics, Documentation Informatics Partners/Interests researcher industrial partner Suitable Information Technology, Statistics, Documentation 1. TECHNOLOGY ENHANCED LEARNING PROCESSES (E-LEARNING AND BEYOND) IN MEDICINE The quality of learning processes in medicine has an immense potential for improvement trough implementation of “information and communication technologies” (as one of the priorities of FP7) in learning and teaching. The learning processes to be considered in this scope are: learning, teaching, administration, collaboration, construction of knowledge and networking of education institutions in medicine. E-learning programme of the European commission has presented clear goals in the development of all the mentioned processes, but their implementation in medicine would require substantial research actions due to several specific features of the area. Three major research subjects in this scope would be: 1. Implementation of E-learning standards/recommendations in medicine 2. Quality of the e-learning resources in medicine 3. Effective implementation of Information and communication technologies (multimedia, interactivity etc.) into medicine education Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Information Technology Research Team Research Team Name Individual Researcher No Research Team Leader Name prof. dr. Uroš Stanič, univ.dipl.ing.el. Contact Person Name prof. dr. Uroš Stanič, univ.dipl.ing.el. Email [email protected] Function Phone +386 4 2569 162 / +386 40 207 103 Fax +386 4 25 69 117 Website http://www.klinika-golnik.si/ Research Team Objectives Main Fields Information Technology, Statistics, Documentation Cybernetics and systems Biomedical technology Telemedicine Partners/Interests Telemedicine Hospital Golnik has strong interest in cooperation in research, development and transfer of good practice in the field of Telemedicine. The application is needed for 24 hours continuous management of pulmonary and allergic patients population in Slovenia with possible exstension of network with neighbouring countries (Austria,Italy, Hungary, Croatia and Western Balkan") and any other interested EU member state and INCO countries." Institution/University Name of Institution/University University Clinic for Respiratory and Allergic Diseases Golnik Number of Employees Number of Researchers Country Slovenia Postal Adress Golnik 36 4204 Golnik Internal Medicine Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD, PhD Igor Aurer Research Team Projects Project Name Diagnostic and treatment of lymphoma Project Leader Prof. Igor Aurer [[email protected]] Project Funding Agency Croatian Ministry of Science Project Budget 75000 € Project Start Date 2002-09-01 Project End Date 2007-09-01 Project Partners Project Summary Lymphoid neoplasms are one of 10 most frequent human tumors and are the only ones of those whose incidence is growing all over the world. Despite treatment a significant number of patients die from their disease or its complications. Because of this are improvements in diagnostic and treatment of lymphoid neoplasms of major scientific and medical importance. The goal of this project is to improve our knowledge on the usefulness of certain diagnostic and therapeutic approaches as well as biologic characteristics of their disease in patients with lymphoid neoplasms. Using a comprehensive team approach we intend to find out: -the prognostic significance of histochemical determination of proliferative indices; -the usefulness of cytology for the diagnosis and classification of lymphoma in comparison with the present golden standard, histology; -the usefulness of US in determining the involvement of cervical and axillary lymph nodes in comparison with the present golden standard, palpation; -the usefulness of positron emission tomography in determining treatment outcome in comparison with the present golden standards, CT scanning and palpation; -the usefulness of monitoring of typical molecular changes in the diagnosis and follow-up of lymphoma; -the usefulness of monitoring of markers of coagulation and anticoagulation system activation for identification of patients with high risk of thrombosis and prevention possibilities. In collaboration with international cooperative groups, specially the EORTC Lymphoma Group, we plan to examine new chemo- and radiotherapeutic treatment approaches for lymphoid neoplasms. The results of this project can improve our understanding of the biology of these diseases, the rational use of diagnostic procedures and treatment outcome in patients with lymphoid neoplasms. Project Website Contact Person Name MD, PhD Igor Aurer Email [email protected] Function Associate Professor of Medicine, Consultatnt Hematologist Phone 385-1-2388-675 Fax 385-1-2421-892 Website mef.hr Research Team Objectives Main Fields Internal Medicine Clinical studies in lymphoma. Biology of lymphomas. Partners/Interests researcher Biology Pathology Internal Medicine Abilities to perform similar studies Clinical and basic studies in lymphoma Institution/University Name of Institution/University Medical School, University of Zagreb Number of Employees n.a. Internal Medicine Number of Researchers n.a. Country Croatia Postal Adress Salata 3 10000 Zagreb Internal Medicine Research Team Research Team Name Academy of Sciences and Arts of the Republic of Srpska/department of cardiovascular pathology Individual Researcher No Research Team Leader Name Associate Professor Dusko Vulic Research Team Members Team Member 0 Professor Nikola Kocev [[email protected]] Team Member 1 Professor Marija Burgic [[email protected]] Team Member 2 Professor Jelena Marinkovic [[email protected]] Team Member 3 Assist.Prof Sinisa Ristic [[email protected]] Team Member 4 Professor Aleksandar Lazarevic [[email protected]] Team Member 5 Ph.D. Dusko Vulic [[email protected]] Team Member 6 Academician Drenka Secerov [[email protected]] Team Member 7 Assis.Prof Snjezana Medenica [[email protected]] Research Team Projects Project Name Education of Medical Doctors and Population in Implementation of Measures for Cardiovascular Diseases Prevention in Republic of Srpska Project Leader Ph.D. Dusko Vulic [[email protected]] Project Funding Agency Health Care Found republic of Srpska Project Budget 25000 € Project Start Date 2001-10-20 Project End Date 2002-10-20 Project Partners Bosnia and Herzegovina/Foundation of health and heart Bosnia and Herzegovina/University of Banja Luka,School of Medicine Banja Luka Bosnia and Herzegovina/University of E.Sarajevo,School of Medicine Foca Project Summary Within the realization of the Program for Prevention of Cardiovascular Diseases in the Republika Srpska,Bosnia and Herzegovina the need for establishing a permanent education of medical doctors and population in implementation of measures for cardiovascular diseases prevention was emphasized in the Guidelines and Recommendations of the National Committee. Given the so-far experience in cooperation with the European Heart Network, European Heart House, World Heart Federation (WHF), RS Ministry of Health and Social Welfare, in organization of the program for education of doctors and population a project has been prepared with the aim of providing education to a group of doctors in primary health care who , as the trainers, perform education of the population on the local level. This form of education conducted in the local communities by means of public discussion on health, school classes dedicated to healthy way of life. Education programs for doctors organized through educational centers (Banja Luka, Prijedor, Doboj, Bijeljina, Srbinje, Trebinje) from where the activities of the trainers in the local communities coordinated. Project Website Project Name Republic of Srpska Coronary Prevention Study Project Leader Ph.D. Dusko Vulic [[email protected]] Project Funding Agency Foundation of health and heart Project Budget 10000 € Project Start Date 2003-06-20 Project End Date 2003-12-20 Project Partners Bosnia and Herzegovina/Foundation of health and heart Bosnia and Herzegovina/Health Care Centres Project Summary our study demonstrated high prevalence of modificable risk factors in coronary heart disease.After Internal Medicine implementation guidelines we changed therapeutic aproach for treatment patient with CHD.It good potential for secundary prevention our population in future.:In our study we analyse 125 patient at 2001/2002 , aged between 40 and 71, 20.8% women and 79.2% men. Foreteen percent of patients smoked cigaretes, 17.6% were overweight (BMI „d 30kg/m2), 63.2% had raised blood pressure (systolic BP„d 140 and/or diastolic BP „d 90mmHg), 52,8% had raised total plasma cholesterol(total cholesterol „d 5,5mmol/l) and 27.2% were diabetic.Reported medication at interview was:antiplatelets drugs 92%,beta-blockers 62,4%,ACE inhibitors 62,4%,lipid-lowering drugs 41,6%,calcium antagonist 16,8%,nitrates 59,4% and antidiabetcs 16,8% two years later after imlementation New Joint European Guidelines. We compared with healthy group and analised population atributive risk(PAR) and we got next results:smoking PAR 32,67%,OR 3,09 CI(1.825.24),psychosocial factor PAR 45.83%,OR 4.84,CI(2.77-8.46),hypertension PAR 10,67%,OR 1.43,CI(0.86-2.84),total cholestaerol PAR 8.19%,OR 1.37,CI(0.83-2,26),diabetes 5,2%,OR 1.57,CI(0.86-2.84) and physical activity 22,72%,OR 0.57,CI(0,29-1.11). Project Website Contact Person Name M.D., Ph.D. Dusko Vulic Email [email protected] Function assistant professor, Phone Fax Website Research Team Objectives Main Fields Internal Medicine Anatomy Public health services Cardiology,Anatomy,Physiology,Psychology,Statistics Partners/Interests researcher Internal Medicine Psychiatry Epidemiology making network between similar research group Project:Postraumatic predictors cardiovascular disease at the younge people Cardiovascular disease (CVD), especially coronary heart disease (CHD) and cerebrovascular disease is one of the most frequent causes of death in Danube Basin countries and in Russia, as it was published in the last statistic WHO year-book. After the decrease of CVD mortality rate in 1980-1990 on the territory of ex Yugoslavia, there was a new trend of increase in Bosnia and Herzegovina, Serbia and Montenegro and Macedonia. Information show that mortality rate in postwar period was 56% in Republic of SrpskaB&H, 57% in Serbia and Montenegro in relation to all other causes of death. The research on coronary heart disease risk factors shows high presence of modifiable risk factors (hypertension, diabetes, hyperlipidaemia and smoking). Taking war into consideration, as well as forced life conditions in Bosnia and Herzegovina in 1992-1996, young population was especially endangered. As this population was continuously exposed to stress, inadequate and irregular nutrition, it is normal to expect a new increase in CVD morbidity and mortality.The hypothesis saying that atherosclerosis starts in childhood is well known. That's why the Yugoslavian study of precursors of atherosclerosis in school children was started in 1997. The study involved 5429 children (2675 boys and 2754 girls), aged 10, in 12 towns in Serbia and 1 town in Republic of Srpska-B&H. The study followed: body weight, height, waist to hip ratio, skin crease on the arm and scapula, blood pressure, sedimentation rate, cholesterol, triglycerides, HDL, LDL, blood glucose, hemoglobin, fibrinogen, leucocytes. The groups are followed for 5 years, with treatment of discovered risk factors. First medical checkups showed significant presence of risk factors in children, as well as that female children have higher values of LDL, triglycerides, Apo-B than male children. Previous analyses of risk factors in coronary heart disease patients showed high incidence of modifiable risk factors, especially smoking, hypertension, diabetes and hyperlipidaemia (ROSCOPS I 2001). Considering forced life conditions, psychosocial factors and lifestyle were major factors for high incidence of these risk factors. Psyche burden induce events that manifest as changes in behavior and habits, and in that way they are in close relation to physical events. Psychosocial factors must be observed comprehensively, taking into consideration continuous stress, sudden stress, bad social situation and unemployment that lead to expressive anxiety, depression and fear. All cited states, which are present in families on this territory, contributed to bad habits like smoking, alcohol abuse, and unhealthy nutrition. All of these Internal Medicine created conditions for faster development of cardiovascular risk factors in young people. That situation caught many people unprepared to resist or to adjust to those tumultuous times. The study was done on the territory of Novi Sad – Serbia and it involved more that 1000 patients with myocardial infarction, 25-64 years old, and it showed that these patients were exposed to stress 4 times more than the control group. Indicators of trends and determinants of CVD development on the territory of Novi Sad show that there was a great increase of myocardial infarction, starting with 1991, which can be related to stress events that caught us. That's why it is necessary to make organized studies of young people with taking measures for prevention and acting on risk factors. By making a uniform system for surveillance of posttraumatic stress disorders and detection of risk factors it would be possible to act at the right time for prevention of consequences and development of CVD and other diseases. That is the only way that could stop the increase of morbidity and mortality of these diseases on the territory of Republic of Srpska. In order to start the system of continuous surveillance of the most endangered population it is necessary to make a network which would include health institutions, schools and faculties, which would organize screening of risk factors with organized work on measures for prevention in schools, faculties and through media. The research would include a sample of 5000 young people in the age of 15-50 that were exposed to forced life conditions during war and in postwar period on the territory of Republic of Srpska. This sample would be followed in 12 centers in Republic of Srpska. The research would be conducted during medical checkups of high school children and students in the time of admission to the first year of study, and the following parameters would be checked: body weight, height, body mass index, waist to hip ratio, blood pressure, EKG, cholesterol, triglycerides, HDL, LDL, blood glucose and PTSP parameters. Values of selected predictors of atherosclerosis would be measured in risk groups. After measurement, data would be recorded to the Project website, and processed afterwards. After the research was conducted and risk groups were defined, preventive measures would be taken through seminars, tribunes and working with risk groups. Selected parameters would be followed in risk groups. For realization of all cited activities it is necessary to develop a network of surveillance centers, to educate personnel, to get all necessary equipment and disposable supplies for surveillance of defined parameters and processing of data by uniform methodology Institution/University Name of Institution/University Banjaluka, university Number of Employees n.a. Number of Researchers n.a. Country Bosnia and Herzegovina Postal Adress 11 71000 B Luka Internal Medicine Research Team Research Team Name Department of Cardiology, Internal Medicine, University Hospital Dubrava Individual Researcher No Research Team Leader Name Professor Mijo Bergovec Research Team Members Team Member 0 MD, MSc Jozica Sikic Vagic [[email protected]] Team Member 1 MD, MSc Boris Starcevic [[email protected]] Team Member 2 MD Hrvoje Vrazic [[email protected]] Team Member 3 MD, MSc Miroslav Raguz [[email protected]] Research Team Projects Project Name Inflammatory markers in acute coronary sydrome Project Leader professor Mijo Bergovec [[email protected]] Project Funding Agency Ministry of Science, Education and Sports Project Budget 20000 € Project Start Date 2004-02-19 Project End Date 2004-11-03 Project Partners Croatia / School of public health "Andrija Stampar" Project Summary During the last decade, more attention is put towards inflammatory factors as on of the components of the patogenesis of acute coronary syndrome. Some studies have shown that the serum levels of some inflammatory markers could be a predictive factor for clinical onset of acute coronary syndrome, and also for the clinical outcome of ACS. Serum levels were measured for the following inflammatory markers: interleukin-6 (IL-6), serum amyloid-A (SA-A), high-sensitivity fraction of Creactive protein (hs-CRP), neopterin and fibrinogen - all of which are highly sensitive proteins of acute inflammatory response, and their serum levels could be potential predictors of extent and outcome of acute coronary syndrome. the study was designed as a prospective study that will include 300 patients with acute coronary syndrome throughout 2 years since the day of admission to the Coronary care unit - which will be the day of patient's enrolment into the study. First patients was enroled on February 19th 2004, and last on November 3rd 2004. Criteria for inclusion were: clear clinical presentation that undisputably shows acute coronary event, characteristic ECG changes, and significant rise in cardioselective enzymes (CK-MB and Troponin I). The data analysis is still in progress and relevant results will be published at and appropriate time. Project Website Contact Person Name Professor Mijo Bergovec Email [email protected] Function Head of Cardiology Department, University Hospital Dubrava Phone +38598228688 Fax +3852902700 Website www.kbd.hr Research Team Objectives Main Fields Internal Medicine Cardiology (invasive-interventional and non-invasive), Internal medicine Partners/Interests researcher Internal Medicine Academic partners willing to collaborate in a regional or subregional international research project in the field of carrdiovascular medicine. Currently we applied for grants for 2 projects to the Croatian ministry of Science, Education and Sports, and are waiting for results of the call for proposals. Also, we applied for SSA under EU FP6 for one project, and are also waiting for result. Internal Medicine Institution/University Name of Institution/University Medical School and Dental School, University of Zagreb Number of Employees 200 Number of Researchers 100 Country Croatia Postal Adress Av. G. Suska 6 10000 Zagreb Internal Medicine Research Team Research Team Name Diabetes and Metabolism Researsch Team, Center for Metabolic Disordes in Diabetes, Institute for Endocrinology, School of Medicine, University of Belgrade Individual Researcher No Research Team Leader Name Professor Nebojsa Lalic Research Team Members Team Member 0 MD Jelena Seferovic [[email protected]] Team Member 1 MD Marija Macesic [[email protected]] Team Member 2 MD, MSc Natasa Rajkovic [[email protected]] Team Member 3 MD, MSc Tanja Milicic [[email protected]] Team Member 4 MD, MSc Ljiljana Lukic [[email protected]] Team Member 5 Assistant Aleksandra Jotic [[email protected]] Team Member 6 Assistant Katarina Lalic [[email protected]] Team Member 7 Professor Miroslava Zamaklar [[email protected]] Research Team Projects Project Name Insulin resistance: the role in the pathogenesis of the onset and progression of neurodegenerative disorders and atherosclerotic vascular disease Project Leader Professor Nebojsa Lalic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Serbia / Institute for Neurology, School of Medicine, University of Belgrade Serbia / Institute for Cardiovascular Diseases, School of Medicine, University of Belgrade Project Summary It has been previously suggested that insulin resistance (IR) exerts an important role in the pathogenesis of both neurodegenerative disorders (NDD) (Alzheimer, Parkinson and Huntington diseases) and atherosclerotic vascular disease (AVD) (ischemic brain, ischemic heart and peripheral vascular diseases). However, both differences and similarities have been reported in the pathogenetic role of IR. In AVD IR induces vascular atherogenesis, while in NDD it potentially exhibits a dual effect: an inhibition of insulin-mediated intracellular metabolism in the brain and an induction of vascular atherogenesis. Those IR-mediated effects might be determined by adipocytokine levels. In this project, the primary objective is a comparative analysis of the relationship between IR and the onset and progression of both NDD and AVD. The secondary objectives include the evaluation of relationship between IR and (1) vascular atherogenic risk factors (endothelial dysfunction, glucose intolerance, dyslipidemias, hypofibrinolysis, inflammatory mediators, total and abdominal obesity and arterial pressure) in AVD; (2) inhibition of insulin action in the brain in NDD; (3) vascular atherogenic risk factors in NDD; (4) insulin and adipocytokine (adiponectin, resistin and leptin) levels in NDD; (5) insulin and adipocytokine levels in AVD. Thus, this research project will provide the design to clarify the pathogenetic relevance of different mechanisms involving IR detectable in NDD and AVD. Project Website www.mntr.sr.gov.yu Contact Person Name Professor Nebojsa Lalic Email [email protected] Function Head of the Center for Metabolic Disorders in Diabetes Phone +381113616317 Fax +381112685393 Website http://www.med.bg.ac.yu/ Internal Medicine Research Team Objectives Main Fields Internal Medicine Immunology and Immunohaematology Therapeutics Insulin resistance, insulin secretion impairements, type 2 diabetes, obesity, prevention of type 2 diabetes, chronic vascular complications of diabetes, type 1 diabetes, prediction and prevention of type 1 diabetes, new oral agents and insulin formulations in diabetes treatment, insulin pumps, islet and pancreas transplantation. Partners/Interests researcher industrial partner Internal Medicine Immunology and Immunohaematology Therapeutics Experience in the field of diabetes and metabolism research and compatibility of interest. Institution/University Name of Institution/University School of Medicine, University of Belgrade Number of Employees 1000 Number of Researchers 850 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Internal Medicine Research Team Research Team Name Endocrine Obesity Individual Researcher No Research Team Leader Name Professor Dragan Micic Research Team Members Team Member 0 MD Danica Stamenkovic-Pejkovic [[email protected]] Team Member 1 Ass. Professor Mirjana Sumarac-Dumanovic [[email protected]] Team Member 2 MD Goran Cvijovic [[email protected]] Team Member 3 Associate Professor Aleksandra Kendereski [[email protected]] Team Member 4 Professor Dragan Micic [[email protected]] Research Team Projects Project Name Endocrine regulatory mechanisms in metabolic disorders Project Leader Professor Dragan Micic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2010-12-31 Project Partners Project Summary The aim of the project is to evaluate model secretion of ghrelin, insulin resistance, adiponectin and CRP in metabolic disorders such as: obesity, metabolic syndrome X and PCOS. These investigations will be performed in basal conditions as well after the performance of adequate therapeutic interventions. These procedures would be performed in regular time intervals: 0.3 and 6 months. Project Website www.mntr.sr.gov.yu Research Team Projects Project Name The role of new secretagogues in control of growth hormone secretion in endocrine disorders Project Leader Professor Dragan Micic [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-01-01 Project End Date 2005-12-31 Project Partners Project Summary During investigation perid we tested the role of new growth hormone secretagogues in different endocrine disorders and results were published in international journals 1: Popovic V, Pekic S, Micic D, Damjanovic S, Marikovic J, Simic M, Dieguez C, Casanueva FF. Evaluation of the reproducibility of the GHRH plus GHRP-6 test of growth hormone reserve in adults. Clin Endocrinol (Oxf). 2004 Feb;60(2):185-91. 2: Micic D, Kendereski A, Sumarac-Dumanovic M, Cvijovic G, Popovic V, Dieguez C, Casanueva F. Growth hormone response to GHRH + GHRP-6 in type 2 diabetes during euglycemic and hyperglycemic clamp. Diabetes Res Clin Pract. 2004 Jan;63(1):37-45. 3: Camina JP, Carreira MC, Micic D, Pombo M, Kelestimur F, Dieguez C, Casanueva FF. Regulation of ghrelin secretion and action. Endocrine. 2003 Oct;22(1):5-12. Review. 4: Popovic V, Pekic S, Doknic M, Micic D, Damjanovic S, Zarkovic M, Aimaretti G, Corneli G, Ghigo E, Deiguez C, Casanueva FF. The effectiveness of arginine + GHRH test compared with GHRH + GHRP-6 test in diagnosing growth hormone deficiency in adults. Clin Endocrinol (Oxf). 2003 Aug;59(2):251-7. 5: Popovic V, Miljic D, Micic D, Damjanovic S, Arvat E, Ghigo E, Dieguez C, Casanueva FF. Ghrelin main action on the regulation of growth hormone release is exerted at hypothalamic level. J Clin Endocrinol Metab. 2003 Jul;88(7):3450-3. 6: Micic D, Sumarac-Dumanovic M, Macut Dj, Kendereski A, Zoric S, Popovic V, Cvijovic G, Dieguez C, Casanueva FF. Growth-hormone response to combined stimulation with GHRH plus GH-releasing peptide-6 in obese patients with polycystic ovary syndrome before and after short-term fasting. J Endocrinol Invest. 2003 Apr;26(4):333-40. Internal Medicine Project Website www.mntr.sr.gov.yu Contact Person Name Professor Dragan Micic Email [email protected] Function Head of the Center for the Metabolic Disorders in Endocrinology Phone 381 11 2 656 527 Fax 381 2 685 357 Website med.bg.ac.yu Research Team Objectives Main Fields Internal Medicine Obesity, PCOS, Metabolic Syndrome, Insulin Resistance, Type 2 Diabetes Mellitus Partners/Interests researcher Endocrinologist, immunologist Internal Medicine We are interested in investigation about possible interplay between ghrelin/leptin/adiponectn/visfatin and Il-cytokine axis. in various autoimune/inflammatory conditions and low grade inflammatory conditions. Institution/University Name of Institution/University School of Medicine, University of Belgrade Number of Employees 800 Number of Researchers 500 Country Serbia and Montenegro Postal Adress Dr Subotica 8 11000 Belgrade Internal Medicine Research Team Research Team Name Infectious agents involved in vessel aging Individual Researcher No Research Team Leader Name Prof. MD Carmen Ardeleanu Contact Person Name Prof. MD Carmen Ardeleanu Email [email protected] Function Head of the Pathology Department Phone +40 21 3192734 Fax +40 21 3192734 Website Research Team Objectives Main Fields Internal Medicine Translating research for human health virus, bacteria, vessels, atheroma, sclerosis, aging Partners/Interests researcher Internal Medicine Objectives: To identify the potential relationship between infectious (viral and bacterial) agents and structural changes in normal or pathological vessel aging. Expected results: Quantification of infectious vascular loading related to structural changes of various cellular types of the microenvironment. Impact: Affordable prevention and treatment of vascular degenerative diseases based on antibiotics or immunotherapy. Contribution to the EU or regional policy: The project´s results will contribute to obtain new knowledges in elucidating the pathogenesis of degenerative changes of vessels in aging and in preventing vascular pathologic aging by means of antiinfectious therapy. European research potential: The actual project may constitute a solid base for improvements of clinical outcomes, with an establishment of standards for normal and pathological structural modifications of vessels in normal and pathological aging. The results may be converted into social and economic benefits of prevention and advanced age disease as vascular cerebral or cardiac diseases. European added value: By creating a multidisciplinary research on vascular aging the project may become a base of an European centre of excellence through collaborative research. Institution/University Name of Institution/University "Victor Babes" National Institute of Pathology Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Spl. Independentei 99-101 50096 Bucharest Internal Medicine Research Team Research Team Name Internal Medicine Individual Researcher No Research Team Leader Name Prof. MD, PhD Breda Pecovnik Balon Research Team Members Team Member 0 mag. Maksimiljan Gorenjak [] Team Member 1 mag. Robert Ekart [] Team Member 2 Prof Radovan Hojs [[email protected]] Contact Person Name Prof. Breda Pecovnik Balon Email [email protected] Function Head Dpt Phone +38623212484 Fax +38623312393 Website uni.mb Research Team Objectives Main Fields Internal Medicine Atherosclerosis, Hemodialysis patients, renal osteodistrophy Partners/Interests researcher hemodialysis patients with vascular calcifications Internal Medicine Radiology CARDIOVASCULAR CALCIFICATIONS IN PATIENTS ON HEMODIALYSIS Calcification is a widespread pathologic process in patients with end-stage renal disease. The most frequent and also clinically most significant are vascular and valvular calcifications. The risk factors are: hypertension, diabetes, hyperlipidemia, smoking, patient age, duration of hemodialysis treatment, hypercalcemia and hyperphosphatemia, receiving of Ca-containing P binders, hyperhomocysteinemia and increased serum fibrinogen, CRP or low albumin levels. Various noninvasive methods have been used to assess and quantify vascular and valvular calcification. Two methods are used most frequently: electron beam computed tomography (EBCT) and multisplice spiral CT. Vascular calcification is also associated with poor outcome in patients with ESRD. It is known that previous myocardial infarction, stenocardia or known coronary disease is associated with increased vascular calcification. It was found a strong association between the presence and extent of vascular calcifications and all-cause and cardiovascular mortality in ESRD patients. However, the fact that inflammation is a protagonist of vascular calcification has been well proved. The impact of inflammation on osteoporosis and vascular calcification can explain the correlation between increased vascular calcification and decreased bone density in dialysis patients. There is also the influence of inhibitors of calcification. One of them is fetuin-A or alfa2-Heremans-Schmid glycoprotein (AHSG). In patients on dialysis treatment the concentration of fetuin-A is lower than in individuals of corresponding sex and age without renal disease. In our research program we will examine hemodialysis patients. We want to demonstrate the influence of risk factors on vascular calcifications (measured by spiral CT) and bone density (measured by DEXA and CT). We will also measured biomarkers of vascular calcifications, including fetuin - A and biochemical markers of inflamation (CRP). We are also interested in prevention of vascular calcification with calcimimetics, sevelamer or analogues of vitamin D. Biphosphonates may also affect the development of calcifications by way of decreasing Ca and P concentrations. Statins can also have a beneficial effect on calcification by decreasing lipid levels. Institution/University Name of Institution/University University Maribor Number of Employees 400 Number of Researchers 20 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Internal Medicine Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Prof Neđad Mulabegović MD PhD Contact Person Name Neđad Mulabegović MD, PhD Email [email protected] Function Head of the Institute of Pharmacology, Clinical Pharmacology and Toxicology Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Internal Medicine Partners/Interests THE IMPACT OF ACE INHIBITORS USE ON MARKERS OF INFLAMMATION AND OXIDATIVE STRESS IN THE METABOLIC SYNDROME BACKGROUND: Individuals with 3 or more of the following clinical features: abdominal obesity, abnormal glucose, low HDL, hypertriglyceridemia and hypertension, have metabolic syndrome. Findings of recent studies have suggested that proinflammatory and prooxidative processes have a significant role in the development and progression of cardiovascular diseases. The renin-angiotensin system (RAS) has a significant role in the pathogenesis of atherosclerosis-related diseases. Angiotensin II is a central molecule in the RAS, and it has numerous effects on uptake, synthesis and oxidation of lipids, inflammation, atherosclerotic plaque formation and progression. OBJECTIVE: To determine whether use of angiotensin-converting enzyme (ACE) inhibitor have impact on markers of inflammation and oxidative stress in subjects with the metabolic syndrome. RESEARCH DESIGN AND METHODS: subjects with at least three out of five diagnostic criteria for metabolic syndrome will be enrolled in the study. Subjects will be randomized in a double-blinded fashion to either enalapril 5 mg/day or matching placebo for 12 weeks. Before and after 12 weeks of enalapril treatment, blood pressure, abdominal girth, serum CRP and 8-isoprostane, fasting HDL cholesterol, triglycerides and glucose will be measured in all subjects. High-sensitivity CRP will be measured with the use of Dade Behring CardioPhase hs CRP reagent by laser nephelometry. Serum 8-isoprostane will be measured by IBL enzyme immunoassay kit for the quantitative determination of STAT – 8 –Isoprostane. EXPECTED RESULTS: Our results could give contribution to the better understanding of actions and effects of ACE inhibitors in the metabolic syndrome. Key words: ACE inhibitors, metabolic syndrome, inflammation, oxidative stress Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Internal Medicine Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Prof.dr Emina NAKAŠ-IĆINDIĆ, MD, PhD Contact Person Name Prof Emina Nakas-Icindic, MD PhD Email [email protected] Function Head of the Department of Human Physiology Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Internal Medicine Partners/Interests Activation of Innate and Adaptive Immune Response by Myocardial Ischemia-Reperfusion Injury in Animal Model Background: Reperfusion injury, which enhances the ischemic injury, is common for revascularization process of myocardial tissue not only in myocardial infarction but also as iatrogenic in open-heart surgery and balloon dilatation (1). This injury to the heart triggers an intense infiltration of white blood cells and release of their enzymes and oxidative radicals that injure healthy heart cells that surround the area of injury. (2) The pathophysiology of ischemia-reperfusion injury and the possible role of innate and acquired immune system have so far not been well characterized. During ischemia the heart may produce endogenous ligands, which activate the immune system or may serve as protective inhibiting leucocytes aggregation. In the heart, there is evidence that toll-like receptors (3) as well as Nuclear Factor kappa-B (4) are activated in chronic heart failure secondary to myocardial ischemia. Furthermore, both factors are involved in the development of arteriosclerosis, where a role immune system is apparent (5). Aim: The aim of this study is to estimate time and place of activation and the role of some particular components of innate and adaptive immune system in myocardial ischemia-reperfusion injury and to identify possible endogenous ligands through studies of cardiomyocytes in culture and co cultures of cardiomyocytes and peripheral blood mononuclear cells (or others, depending on findings above). Methods and techniques: The experiments will be conducted in vivo (mice), isolated heart and in tissue cultures. Immunohistochemistry of myocardial tissue will be used to evaluate cell infiltration in scar tissue and cellular localization, analysis of activation of circulating white blood cell populations with flow cytometry. Immunoblotting of myocardial protein extracts to evaluate activation of toll-like and NOD receptors, and mitogen activated protein kinases, as well as studies of gene expression in extracts of hearts and circulating cells of RNA corresponding to the proteins found. Studies of cardiomyocytes in culture and co cultures of cardiomyocytes and peripheral blood mononuclear cells (or others, depending on findings above) are needed to identify some possible endogenous ligands. After getting good quantity and quality of isolated mouse cardiomyocytes, signal transduction pathways after different stimuli such as anoxia, cytokine stimulation, and heat shock proteins will be tested. Expected results The research on innate and adaptive immune system activation in response to myocardial ischemia-reperfusion injury in animal model could help to elicit the role of innate and adaptive immunity in humans in order to maximize tissue recovery and to reduce collateral damage. References: 1. “A review of leukofiltration in cardiac surgery: the time course of reperfusion injury may facilitate study design of anti-inflammatory effects”, Hodder Arnold Journals, Perfusion, Volume 17, Supplement 1, 1 May 2002, pp 53-62. 2. Lindsey M. Et Al. “Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia-reperfusion. “, Circulation 103:2181-2187, 2001. 3.Toll-like receptor 4 mediates ischemia/reperfusion injury of the heart Chong et al. J Thorac Cardiovasc Surg.2004; 128: 170-179 4.Valen G, Yan Z-Q, Hansson GK. Nuclear Factor kappa-B and the heart. Journal of American College of Cardiology 2001;38;307-314. 5. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352:1685 Internal Medicine Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Internal Medicine Research Team Research Team Name Individual Researcher No Research Team Leader Name Dr sci. Elma KUČUKALIĆ-SELIMOVIĆ Research Team Members Team Member 0 Beslic S. Team Member 1 Basic H. Team Member 2 Beslic N. Team Member 3 Bilalovic N. Team Member 4 Secic S. Team Member 5 Beslija S. Team Member 6 Milardovic R. Team Member 7 Kapetanovic E. Team Member 8 Tatarevic A. Team Member 9 Hadzimuratovic S. Team Member 10 Balta E. Team Member 11 Mahic N. Team Member 12 Begic A. Team Member 13 Muftic K. Contact Person Name Dr sci. Elma KUČUKALIĆ-SELIMOVIĆ Email [email protected] Function docent, Department of Internal Medicine and Clinics of Propaedeutics Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Internal Medicine Partners/Interests Evaluation of the SLN Biopsy Impact on Incidence and Localisation of the Recurant Desease in Patients with Breast Cancer The current standard approach to determine the spread of breast cancer is an ALD (axillary lymph node dissection), the surgical procedure that carries with it risk of postoperative morbidity. SLN (sentinel lymph node) biopsy is reliable method in detecting the spread of breast cancer which can enable ALD to be avoided and that is why this method is considered as important in the management of breast cancer patients. Crucial parameter concerning the accuracy of SLN biopsy in breast cancer surgery is the impact of this procedure on the long term clinical outcome of patients. AIM: To evaluate correlation of both tumour size and tumour type in regard to negative SLN on the development of the recurrent disease and to define the impact of this procedure on the long-term clinical outcome of the patients. PATIENTS AND METHODS: • The study would be multidisciplinary, prospective randomised trial including patients with operable breast carcinoma and clinically negative axillary lymph nodes (T 1-2 N0 M0). • Patients should be referred for lymph node scintigraphy prior to surgery. • On the surgery, on base of the SLN intraoperative frozen section hystopatological result, operation will be adequately completed. • Only SLN negative patients should be included in the trial. • Oncologycal treatment will follow the recommended protocol for curtain cases. Internal Medicine • The data should be analysed after 2 and 4 years long follow up. EXPECTED RESULTS: It is very likely that T1 breast cancer with a negative SLN will not develop tumour recurrence in proposed follow up period. But, influence of negative SLN on disease free period is not completely clear and we would like to contribute clarification of this issue which is very important in sense of predictability of disease outcome. In this regard performance of SLN biopsy without subsequent axillary clearance requires adequate follow up. LITERATURE: 1. Mariani G, et al. Radioguided Sentinel Lymph Node Biopsy in Brest Cancer Surgery. Eur J Nucl Med. 2001; 42; 1198-1213. 2. Veronesi U,Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet 1997; 349: 1864-1867. 3. Veronesi U, Luini A, Galimberti V, Marchini S, Sacchini V, Rilke F. Extent of metastatic axillary involvment in 1446 cases of breast cancer. Eur J Surg Oncol. 1990;16:127-133. 4. Djulbegovic B., D.M.Sullivan Decision Making in Oncology Evidence Based Management. Churchill Livingstone, 1997; 253 –275. Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Internal Medicine Research Team Research Team Name Individual Researcher No Research Team Leader Name Prof, MD PhD Bakir Mehić Contact Person Name Prof, MD PhD Bakir Mehić Email [email protected] Function Vice Dean Phone +38733444343 Fax +38733272691 Website mf.unsa.ba Research Team Objectives Main Fields Internal Medicine Partners/Interests THE PRECANCEROUSES OF BRONCHIAL MUCOSA IN SMOKERS AND COPD PATIENTS IN SOUTHEAST EUROPEAN COUNTRIES Background: The identification of abnormal or suspicious areas in tracheobronchial tree by autofluorescence bronchoscopy (AFB) is possible, even the white light bronchoscopy (WLB) examination stay as a normal. Bronchial lesions in smokers and patients with different stages of COPD depend from duration and quantity of the exposition to the risk factors. Main goals: To determine the frequency of metaplasia, dysplasia and carcinoma in particular stages of COPD in Southeast European countries. To compare the duration of exposure to risk factors with histological picture of metaplasia, dysplasia and carcinoma in Southeast European countries. To compare the COPD stages with the frequency of histological picture of metaplasia, dysplasia and carcinoma. Methods: Both, WLB and AFB will be performing with the aim of detection of precancerous and cancerous bronchial lesions in patients with different stages of COPD (by GOLD). The biopsy specimens will be taken in areas of tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. Histological data will be comparing with the stage of COPD as well as with duration and quantity of exposure to risk factors (smoking, professional pollution etc). Anticipated results: There is very similar prevalence of smoking in Southeast countries. The question is: are there significant differences between the consequences of smoking in separate country centers? Institution/University Name of Institution/University Medical Faculty University of Sarajevo Number of Employees 382 Number of Researchers 104 Country Bosnia-Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Internal Medicine Research Team Research Team Name Individual Researcher No Research Team Leader Name Prof. Dr. Hellmut Samonigg Contact Person Name Prof. Dr. Hellmut Samonigg Email [email protected] Function vice dean for strategy and innovation, head of the department of oncology Phone +43 316 385 3115 Fax +43 316 385 4167 Website http://www.onkologie-graz.at/ Research Team Objectives Main Fields Internal Medicine Oncology Cancer Partners/Interests Oncology Cancer Institution/University Name of Institution/University Clinical Department of Oncology, Internal Medicine, Medical University of Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 15 8036 Graz Microbiology Research Team Research Team Name Department of Microbiology Individual Researcher No Research Team Leader Name MD, PhD Maja Abram Research Team Members Team Member 0 MD, PhD Darinka Vuckovic [[email protected]] Team Member 1 MD, PhD Tomislav Rukavina [[email protected]] Team Member 2 MD, PhD Brigita Ticac [[email protected]] Team Member 3 MD, MSc Marina Bubonja [[email protected]] Team Member 4 MD, PhD Miljenko Doric [[email protected]] Team Member 5 Sanit.Eng., PhD Marina Santic [[email protected]] Team Member 6 MD Roberta Rubesa-Mihaljevic [[email protected]] Team Member 7 MD Ivana Skrobonja [[email protected]] Team Member 8 Sanit. Eng. Vanja Marchesi [[email protected]] Team Member 9 Sanit.Eng, MSc Ivana Gobin [[email protected]] Team Member 10 MD Mirela Markanovic [ [email protected] ] Research Team Projects Project Name Experimental Listeria monocytogenes infection during pregnancy Project Leader prof., MD, PhD Maja Abram [[email protected]] Project Funding Agency Croatian Ministry of Science Project Budget 10.000 € Project Start Date 2002-07-01 Project End Date 2006-12-31 Project Partners Germany, University of Cologne, Dpt. Neuropathology Slovenia, University of Ljubljana, Institute of Microbiology and Immunology Project Summary Investigation of cellular and molecular mechanisms which are of importance for the pathogenesis of congenital listeriosis; determination of specific modulation in the cytokine/chemokine production at the systemic and local level; using animal model, recovery from listeriosis, resistance mechanisms, the fetal and maternal contribution to the cytokine/chemokine milieu are followed. Project Website Project Name Resistance and virulence of Campylobacter Project Leader prof. MD, PhD Maja Abram [[email protected]] Project Funding Agency Croatian and Slovenian Ministry of Science Project Budget 2.000 € Project Start Date 2004-01-01 Project End Date 2005-12-31 Project Partners Slovenia, University of Ljubljana, Biotechnical Faculty, Dpt.of Microbiology Project Summary In vitro evaluation of viability and virulence of experimentally stressed Campylobacter jejuni; ability of Campylobacter jejuni to invade and survive in mammalian cells in vitro; Host resistance to primary and secondary Campylobacter jejuni infections in C57Bl/6 mice. Project Website Project Name Pathogenesis of experimental legionellosis Project Leader prof, MD, PhD Miljenko Doric [[email protected]] Project Funding Agency Croatian Ministry of Science Microbiology Project Budget 15.000 € Project Start Date 2002-07-01 Project End Date 2006-12-31 Project Partners Austria, University of Graz, Institute for Hygiene USA, University of Louisville, Dpt. Microbiology Project Summary Using an experimental model on A/J mice histopathology of Legionnaires' disease and the role of different T cell subsets were analyzed; the differences in the cytopathogenic capacity of different Legionella species are investigated. Project Website Project Name Antilipopolisacharide immunity during Klebsiella infection Project Leader prof, MD, PhD Tomislav Rukavina [[email protected]] Project Funding Agency Croatian Ministry of Science Project Budget 18.000 € Project Start Date 2002-07-01 Project End Date 2006-12-31 Project Partners Project Summary Determination of cell surface receptor signals involved in anti-LPS mediated protection in an animal model of systemic Klebsiella infection; cytokine pattern associated with the survival of animals protected with anti-LPS antibodies. Project Website Contact Person Name MD, PhD Maja Abram Email [email protected] Function Associate professor Phone +385 51 651 172 Fax +385 51 651 177 Website medr.hr Research Team Objectives Main Fields Microbiology Immunology and Immunohaematology Clinical microbiology Investigation on the pathogenesis of infectious diseases focusing on particular infectious agents: L. pneumophila, L. monocytogenes, C. jejuni, K. pneumoniae, F. tularensis; host response to bacterial pathogens; cellular and molecular mechanisms in host-bacteria relationship; a variety of experimental approaches from animal model, cell cultures to isolated cells are used. Partners/Interests researcher Microbiology Immunology and Immunohaematology Clinical microbiology - cellular microbiology-a molecular understanding of cellular processes that allow microbes to compete and survive in their host - genotyping of clinical, enivronmental and food isolates Continuation in studying the properties of the pathogens associated with infectious diseases which have a significant impact on public health: legionelloses, listeriosis, tularemia, campylobacteriosis and gram-negative sepsis; Established experimental models (in vivo mouse infection; cell-cultures) will serve as the basis for our future studies on the properties of pathogens, as well as, investigation of the host's susceptibility to infection and the ability of the immune system to control or eliminate the microorganisms. Institution/University Name of Institution/University Dpt. Microbiology, Medical Faculty, University of Rijeka Number of Employees 20 Microbiology Number of Researchers 11 Country Croatia Postal Adress Brace Branchetta 20 51000 Rijeka Microbiology Research Team Research Team Name Individual Researcher No Research Team Leader Name prof. dr. Stanislav Šuškovič, dr.med., spec Contact Person Name prof. dr. Stanislav Šuškovič, dr.med., spec Email [email protected] Function Phone +386 4 25 69 383 Fax +386 4 25 69 117 Website http://www.klinika-golnik.si/ Research Team Objectives Main Fields Microbiology Immunology Partners/Interests Microbiology Immunology Epidemiologic data of COPD or asthma are badly needed in Slovenia. We intend to perform relevant epidemiological studies in cooperation with the experts from the Institute of Public Health of the Republic of Slovenia. Institution/University Name of Institution/University University Clinic for Respiratory and Allergic Diseases Golnik Number of Employees Number of Researchers Country Slovenia Postal Adress Golnik 36 4204 Golnik Microbiology Research Team Research Team Name Individual Researcher No Research Team Leader Name dr. Peter Korosec Contact Person Name dr. Peter Korosec Email [email protected] Function Phone +386 4 25 69 100 Fax +386 4 25 69 117 Website http://www.klinika-golnik.si/ Research Team Objectives Main Fields Microbiology Immunology Partners/Interests Microbiology Immunology We would be pleased to collaborate with those who might be interested in this topic. Expression of COX-1 and -2 in monocytes of aspirin-int olerant(AI) patients The aim of our study is to find out whether it would be possible to identify aspirin-intolerant patients by measuring the expression of COX 1 and/or 2 in peripheral-blood monocytes, therefore without clinical provocation. We incubate samples of AI patients (and controls) venous blood with either 1.nothing added, 2. LPS added (activation), 3. LPS + aspirin added and 4. only aspirin added. We then lyse erythrocytes and stain COX-1 and 2 by intracellular staining with marked monoclonal antibodies. Monocytes are also marked with anti-CD 14 antibodies. Levels of expression are measured by flow cytometry. Our hypothesis is that COX-1 expression remains invariated in all cases, and that COX-2 expression in LPS-stimulated (but not unstimulated) monocytes exposed to aspirin in AI patients is significantly higher than the level of COX-2 expression in healthy controls. Institution/University Name of Institution/University University Clinic for Respiratory and Allergic Diseases Golnik Number of Employees Number of Researchers Country Slovenia Postal Adress Golnik 36 4204 Golnik Microbiology Research Team Research Team Name Individual Researcher No Research Team Leader Name dr. Marc Malovrh Mateja Research Team Members Team Member 0 Sabina Skrgat [[email protected]] Contact Person Name dr. Marc Malovrh Mateja Email [email protected] Function Phone +386 4 25 69 100 Fax +386 4 25 69 117 Website http://www.klinika-golnik.si/ Research Team Objectives Main Fields Microbiology Immunology Partners/Interests Microbiology Immunology The in vivo and in vitro results propose the involvement of anaphylatoxins and angiogenetic factors in the pathogenesis of COPD. Our aim is to determine the levels of anaphylatoxins (C5a, C4a, and C3a) and angiogenetic factors (VEGF, angiogenin, bFGF, IL8, TNF) at the site of inflammation in stable COPD (concentrating on the correlation of C5a or angiogenetic factors concentrations with the extensity of emphysema), in exacerbation of a disease and in healthy smokers. We measure the concentrations of anaphylatoxins and angiogenetic factors in the induced sputum by cytometric bead array method (CBA). Institution/University Name of Institution/University University Clinic for Respiratory and Allergic Diseases Golnik Number of Employees Number of Researchers Country Slovenia Postal Adress Golnik 36 4204 Golnik Neurology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Professor, MD, PhD Marin Stancic Contact Person Name Professor, MD, PhD Marin Stancic Email [email protected] Function Dept. Chief, Universiyt Hospital of Traumatology Zagreb Phone +385 1 46 97 139 Fax +385 1 46 10 365 Website www.trauma.hr Research Team Objectives Main Fields Neurology Surgery Anatomy 1. anatomy and regeneration of peripheral nerves 2. biomechanics of the spine Partners/Interests researcher Anatomy Surgery Psychiatry interested in collaboration in the projects in the indicated scientific fields anatomy and regeneration of peripheral nerves biomechanics of the spine Institution/University Name of Institution/University University Hospital of Traumatology Zagreb Number of Employees 452 Number of Researchers 18 Country Croatia Postal Adress Draskoviceva 19 10000 Zagreb Neurology Research Team Research Team Name Group for Neurodegenerative Disorders (Institute of Neurology CCS, Medical School Belgrade) Individual Researcher No Research Team Leader Name Prof Kostić Vladimir Research Team Members Team Member 0 Assoc Prof Svetel Marina [[email protected]] Team Member 1 Assoc Prof Stefanova Elka [[email protected]] Team Member 2 Assist Prof Dragašević Nataša [[email protected]] Team Member 3 dr med Petrović Igor [[email protected]] Team Member 4 Assoc Prof Marković Ivanka [[email protected]] Team Member 5 Associ Prof Novaković Ivana [[email protected]] Team Member 6 Researcher Radovanović Saša [[email protected]] Team Member 7 Junior Researcher Marić Jelena [[email protected]] Team Member 8 Prof Pekmezović Tanja [[email protected]] Team Member 9 Prof Kostić Vladimir [[email protected]] Contact Person Name Prof Kostić Vladimir Email [email protected] Function Head, Institute of Neurology CCS Phone 381-11-2685596 Fax 381-11-2684577 Website www.med.fak.bg.ac.yu Research Team Objectives Main Fields Neurology Genetics Epidemiology 1. Genetics of movement disorders (Parkinson'disease, dystonia, Wilson's disease, spinocerebellar ataxia) and genotype/phenotype correlations 2. Non-motor problems in Parkinson's disease and atypical parkinsonism (MSA, PSP, vascular parkinsonism), particularly depression and dementia 3. Epidemiology of dystonia, parkinsonism, spinocerebellar ataxia and other neurodegenerative disorders Partners/Interests researcher Genetics Physiology Neurology 1. possibilities for mor advanced genetical investigation and expertise in degenerative disorders 1. Investigation of the possible genetic and biochemical, as well as clinical correlates of non-motor symptoms in Parkinson's disease and parkinsonism 2. Genotype/phenotype correlation in neurodegenerative disorders Institution/University Name of Institution/University Medical School University of Belgrade Number of Employees 900 Number of Researchers 450 Country Serbia and Montenegro Postal Adress ul. dr Subotića 8 11000 Belgrade Obstetrics and Gynaecology Research Team Research Team Name Reproductive Medicine and Gynecologic Endocrinology Individual Researcher No Research Team Leader Name Mr. MD, PhD Veljko Vlaisavljevic Research Team Members Team Member 0 Mr. MD, PhD Veljko Vlaisavljevic [[email protected]] Team Member 1 Mr., MD, PhD Borut Kovacic [[email protected]] Contact Person Name Mr. MD, PhD Veljko Vlaisavljeviæ Email [email protected] Function Head of Department of Reproductive Medicine and Gynecologic Endoc Phone +386 2 321 24 89 Fax +386 2 331 23 93 Website http://www.ivf-mb.net Research Team Objectives Main Fields Obstetrics and Gynaecology Reproductive Medicine and Gynecologic Endocrinology Partners/Interests researcher Suitable Obstetrics and Gynaecology Chromosomal abnormalities in embryos from natural and IVM cycles and identification of specific proteins characteristic for human blastomere and stem cells diferentiation. The cells of early preimplantation embryos are totipotent (autonomous capability to develop to the embryo). The loss of some cells from the early embryo does not threats its vitality. This embryo ability is exploited in many assisted reproductive techniques. In preimplantation genetic diagnosis (PGD) one or two cells are taken from 8 cell embryo for genetic analysis. In embryo freezing also happens frequently that some blastomeres do not survive the procedure.. New discoveries on mouse embryos prove, that only the cells from 2 – 4 cell embryos are totipotent. Later stages have the blastomeres still predetermined for the diferentiation into extra-embryonic and embryonic cell lines. This was confirmed by the presence of Oct-4 in the cells, protein which is known only for pluripotent embryonic cell line.. The embryos obtained by the procedure of in vitro maturation (IVM) of oocytes, have more nuclear abnormalities and also more frequently arrest in the development than the embryos from classic in vitro fertilization (IVF) procedure . The frequency of such abnormalities in embryos from natural IVF cycle is not known. From this reason it prevails the opinion, that before the embryotransfer these embryos should be screened for aneuploidies by PGD. The knowledge about the stage in which the blastomeres are still totipotent, should enable, that PGD will be performed before the cell diferentiation. In such a manner we could be sure that the embryo will not be additionally affected by the biopsy of blastomeres. Anticipated results : Aim of the study is to ascertain the details about the frequeny of chromosomal abnormalities in embryos coming from natural and IVM cycles and ascertain the beginning of human blastomere differentiation The confirmation of OCT-4 protein also in the human 8-cell embryos would mean, that the blastomeres of 8-cell embryo are still differentiated. This information could cause the redefinition of the safety of some assisted reproductive technologies, which exploite individual cells for the diagnosis. Some cells from clinically not utilized human embryos from an IVF/ICSI programe, which arrest in various stages (2, 4, 8, >8 cell stage), will be analyzed for the expression of genes, responsible for the differentiation or for pluripotency. The stage in which the human embryo starts to differentiate will be determined. These informations are important for reproductive medicine, because the embryo stage in which the biopsy of blastomeres is still acceptable, must be exactly known. The results will be helpfull for the estimation of the potential of embryonic cells for the derivation of embryonic stem cells. Institution/University Name of Institution/University Maribor Teaching Hospital Number of Employees 2400 Number of Researchers 33 Obstetrics and Gynaecology Country Slovenia Postal Adress Ljubljanska 5 2000 Maribor Other Allied Sciences Research Team Research Team Name Institute of Forensic Medicine and Criminology, Medical School University of Zagreb, Croatia Individual Researcher No Research Team Leader Name Professor, MD, PhD Davor Strinovic Research Team Members Team Member 0 MD, PhD, Assist.Prof Milovan Kubat [[email protected]] Team Member 1 PhD, Assoc. Prof. Mario Slaus [[email protected]] Team Member 2 MD, PhD, Senior Ass. Vedrana Petrovecki [[email protected]] Team Member 3 MD, MSc, Junior Ass. Davor Mayer [[email protected]] Contact Person Name Professor, MD, PhD Davor Strinovic Email [email protected] Function Professor of Forensic Medicine Phone +385 1 4566 827 Fax +385 1 4590 221 Website www.mef.hr Research Team Objectives Main Fields Other allied sciences Work in the field of Forensic Medicine. Identification process of recovered human remains. Establishing anthropometric (age, gender, height) and medicolegal (injuries, cause of death) characteristics of exhumated individuals. Identification of the deceased using "classical" methods in forensic medicine as well as forensic genotyping (DNA anaysis). Dealing with victims of mass disasters in civil circumstances (e.g. traffic accidents). Partners/Interests researcher Other allied sciences Partners of the corresponding profiles. Projects focused on identification of victims in mass disasters. Institution/University Name of Institution/University Dept of Forensic Medicine, Medical School University of Zagreb Number of Employees 25 Number of Researchers 6 Country Croatia Postal Adress Salata 11 10000 Zagreb Pathology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD PhD Marin Nola Research Team Members Team Member 0 MD Alinda Varnai [] Team Member 1 Prof, MD, PhD, Ivan Damjanov [] Team Member 2 Mr sci Tomièic Ivana [] Team Member 3 MD, Mr sci Blažanovic Anto [] Team Member 4 Mr sci Koraljka Gjadrov [] Team Member 5 Mr sci Mirela Mirt [] Team Member 6 MD, PhD Tvrtko Hudolin [] Team Member 7 Prof, MD, PhD Igor Aurer [] Team Member 8 MD László Pajor [] Team Member 9 MD, PhD Nurija Bilalovic [] Research Team Projects Project Name CD 43 - prognostic marker for the outcome of lymphoma patients Project Leader MD, PhD Marin Nola [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-00-00 Project End Date 2011-00-00 Project Partners Project Summary CD43 is expressed on the surface of all white blood cells, except on the surface of non-activated mature B-cells. Simultaneous expression of CD43 and CD20 on B-lymphocytes is considered to be extremely useful in distinguishing B-cell non-Hodgkin lymphomas from non-neoplastic lymphoid proliferations. Positive expression of this marker is found in 75-85% of lymphoblastic lymphomas/leukemias, and some nonlymphoblastic T-cell non-Hodgkin lymphoma such as mycosis fungoides, non-epidermotropic T-cell lymphoma of the skin, peripheral T-cell lymphoma, and anaplastic large cell lymphoma. Positive expression of CD43 is also found in 30% of nonlymphoblastic B-cell, non-Hodgkin lymphomas. That group includes patients with small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma and diffuse large B-cell lymphoma. CD43 is positive in 50% of plasmacytomas and multiple myelomas. It is well known that lymphomas, depending of the mutations, express or lose certain markers on the cell surfaces. Therefore, expression of CD43 in some types of lymphomas could predict better or poorer outcome of patients. Second part of the study would investigate connection of certain infections with development of lymphomas, reaction of patients to therapy an connection of these lymphomas with CD43. Since a certain number of MALT lymphomas are resistant to therapy and have a tendency of transformation to diffuse large B-cell lymphoma, it is necessary to recognize that group of patients. We assume that transformation occurs because of genetic characteristics of certain bacteria, as well as genetic characteristics of the infected host. Resistance of H. pylori to macrolide antibiotics is very significant clinically, but there is no research that deals with connection of resistance to macrolides to MALT lymphomas and DLBCL. Our goal is to establish the occurence of mutations in 23S rRNA region of H. pylori genome that is responsible for the resistance to macrolides, and possibly use those mutations as a bacterial marker/marker of MALT lymphomas that undergo transformation to DLBCL. We would also investigate possible connection between bacterial mutations and Bcl10, MALT1 and CARMA1 genes of the host. Third part of the study would include flow cytometric and PCR analysis of DNA, as well as the most common translocations in lymphoid neoplasms, as well as their connection with CD43 positive as opposed to CD43 negative lymphoid neoplasms. Project Website Pathology Contact Person Name MD PhD Marin Nola Email [email protected] Function Associate Professor Phone 385-1-2388-089 Fax 385-1-4921-151 Website none Research Team Objectives Main Fields Pathology Internal Medicine hematopathology, hematology, surgical pathology, cytopathology, molecular biology, urology, Partners/Interests researcher industrial partner Pathology Internal Medicine researcher - lymphoma cases stored as paraffin blocks industrial partner - some new antigens for probe on lymphoma cases CD43 is expressed on the surface of all white blood cells, except on the surface of non-activated mature B-cells. Simultaneous expression of CD43 and CD20 on B-lymphocytes is considered to be extremely useful in distinguishing B-cell non-Hodgkin lymphomas from non-neoplastic lymphoid proliferations. Positive expression of this marker is found in 75-85% of lymphoblastic lymphomas/leukemias, and some nonlymphoblastic T-cell non-Hodgkin lymphoma such as mycosis fungoides, non-epidermotropic T-cell lymphoma of the skin, peripheral T-cell lymphoma, and anaplastic large cell lymphoma. Positive expression of CD43 is also found in 30% of nonlymphoblastic B-cell, non-Hodgkin lymphomas. That group includes patients with small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma and diffuse large B-cell lymphoma. CD43 is positive in 50% of plasmacytomas and multiple myelomas. It is well known that lymphomas, depending of the mutations, express or lose certain markers on the cell surfaces. Therefore, expression of CD43 in some types of lymphomas could predict better or poorer outcome of patients. Second part of the study would investigate connection of certain infections with development of lymphomas, reaction of patients to therapy an connection of these lymphomas with CD43. Since a certain number of MALT lymphomas are resistant to therapy and have a tendency of transformation to diffuse large B-cell lymphoma, it is necessary to recognize that group of patients. We assume that transformation occurs because of genetic characteristics of certain bacteria, as well as genetic characteristics of the infected host. Resistance of H. pylori to macrolide antibiotics is very significant clinically, but there is no research that deals with connection of resistance to macrolides to MALT lymphomas and DLBCL. Our goal is to establish the occurence of mutations in 23S rRNA region of H. pylori genome that is responsible for the resistance to macrolides, and possibly use those mutations as a bacterial marker/marker of MALT lymphomas that undergo transformation to DLBCL. We would also investigate possible connection between bacterial mutations and Bcl10, MALT1 and CARMA1 genes of the host. Third part of the study would include flow cytometric and PCR analysis of DNA, as well as the most common translocations in lymphoid neoplasms, as well as their connection with CD43 positive as opposed to CD43 negative lymphoid neoplasms. Institution/University Name of Institution/University Medical University of Zagreb Number of Employees n.a. Number of Researchers n.a. Country Croatia Postal Adress Salata 10 10000 Zagreb Pathology Research Team Research Team Name Improvement of therapeutical approach by molecular assessment of malignant soft tissue tumors Individual Researcher No Research Team Leader Name Dr. Cristina Iosif Contact Person Name Dr. Cristina Iosif Email [email protected] Function Project Director Phone +40 21 3192734 Fax +40 21 3192734 Website Research Team Objectives Main Fields Pathology soft tissue tumors therapy Partners/Interests researcher Pathology Malignant soft tissue tumors are rare but usually aggressive and resistant to the classical antitumoral drugs. The project aims to identify new tumoral or stromal markers as molecular targets for novel specific therapies. This approach increases the translational character of the basic research. Objectives: To develop new therapeutic strategies in malignant soft tissue tumors by molecular characterization of stromal cells and vessels in correlation with activators expression. Expected results: Improvement of specific antitumor therapy using a new molecular approach. Contribution to the EU or regional policy: The project will generate new points of view and new approaching policies about applying novel therapeutic strategies in the management of populational health. The project may be included in European objective of dynamic and competitive knowledge-based economy. European research potential: The project realization is ensured by its competitive potential in a challenging field of molecular based therapies, making possible an excellent translational research with real economic benefit. European added value: As an optimal research base with multidisciplinary framework, this project is open to collaborative research with European centers of excellence. Institution/University Name of Institution/University "Victor Babes" National Institute of Pathology Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Spl. Independentei 99-101 50096 Bucharest Pathology Research Team Research Team Name Quantitative analysis and image transmission divission, Institute of Pathology Medical Faculty University of Zagreb Individual Researcher No Research Team Leader Name MD, PhD Sven Seiwerth Research Team Members Team Member 0 MD Sanja Radeljak [[email protected]] Team Member 1 MD Vlasta Loncaric [] Team Member 2 MD Natasa Crne [] Team Member 3 MD Luka Brcic [[email protected]] Team Member 4 MD Lovorka Batelja Vuletic [[email protected]] Team Member 5 MD, PhD Sven Seiwerth [[email protected]] Research Team Projects Project Name Quantitative analysis and image transmission in pathology Project Leader MD, PhD Sven Seiwerth [[email protected]] Project Funding Agency Ministry of science, education and sport Project Budget 25000 € Project Start Date 2002-10-22 Project End Date 2006-10-22 Project Partners Project Summary Pathology is one of the most important diagnostic disciplines giving expertise in everyday routine as well as in experimental work. Based on pathological diagnosis often additonal chemo or radiation therapy is planed. Recently, great efforts are made to add more objective elements into the histopathological diagnosis. This is mostly done by measurements or quantitation (e.g. counting of positive lymph nods, largest tumor diameter etc.) A further step is made by quantification of microscopical parameters (nuclear measuremnts, density of nuclei , DNA content etc.). Quantification on histological slides is stil not widely used and only few parameters are routinely quantitated on this level. GOAL of this study is to show, on different models, the possibility and usefullness of morphometrical analysis of histological preparations and to introduce some of them into routine work. MODELS to be used in this work are: estimation of prognostic walues of immunoreactivity for cathepsin D, cyclin D1, nm23 in laryngeal cancer tissue, especially with respect to intratumoral heterogeneity. Flow citometric analysis of the same tissue and LOH analysis will also be performed. Secondly, morphometric analysis of pigmented skin lesions concerning nuclear parameters and distribution will be performed using artificial inteligence and machine learning procedures. The studies are planed as multicentric and international including Zagreb, Slavonski Brod, Amsterdam, Nejmegen, and Budapest). Thes second part of the project concerns experimental work on animal models of disease in the study of new peptides and new surgical procedures. This part is closely associated with other projects of MZT and departements of our University. The third part includes the continuation of the project on telepathology by establishing a pilot study on telediagnosis on intraoperative frozen sections. This pilot includes also a quality and feasibility study. The telpathoogy link is proposed between a county hospital (Ogulin) and the University departement. POTENTIAL BENEFITS: of these studies is a more precise diagnosis or prognosis of malignant tumors enabling a more individualised therapeutic approach. The experimental part is supposed to yield some new therapeutic drugs and intraoperative telediagnosis will certanly increase the quality of treatment in the respective hospital. In this sence the educational potential of tlepathology shuld not be neglected. Project Website www.mzos.hr Contact Person Name MD, PhD Sven Seiwerth Email [email protected] Function Professor Phone +38514566977 Fax +38514921151 Pathology Website www.mef.hr Research Team Objectives Main Fields Pathology Pharmacology Quantitative analysis in tumor and experimental pathology. Prognostic factors in tumor pathology. Angiogenesis. Wound healing. Telepathology. Partners/Interests researcher industrial partner Pathology Pharmacology Information Technology, Statistics, Documentation Should have knowledge in molecular biology and its methods, applicable in molecular pathology. New technology in microscopy for testing. Continuing research in the field of tumors, (especially prognostic factors and tumor heterogeneity) wound healing and angiogenesis. Institution/University Name of Institution/University University of Zagreb Medical School , Department of Pathology Number of Employees 45 Number of Researchers 13 Country Croatia Postal Adress Salata 10 10000 Zagreb Pathology Research Team Research Team Name Translating histogenetic and molecular variability of CD117 in human tumors to the innovative targeted therapies Individual Researcher No Research Team Leader Name Prof. MD Carmen Ardeleanu Contact Person Name Prof. MD Carmen Ardeleanu Email [email protected] Function Head of the Pathology Department Phone +40 21 3192734 Fax +40 21 3192734 Website Research Team Objectives Main Fields Pathology Translating research for human health CD117, genomics, human tumors, targeted therapy Partners/Interests researcher Pathology Objectives: To improve a targeted antitumor therapy by identifying histogenetic and molecular variability of CD117 in human tumors. The expected results: A better characterization of human tumors with alterations in CD117, by means of molecular analysis aiming optimal targeted therapy. The impact of the project: Optimal and efficient treatment of CD117 defective tumors based on molecular selection. Contribution to the EU or regional policy: Updating knowledges about the signal transduction pathways in human tumors and upgrading a molecular diagnosis and targeted therapy, with impact on public health. European research potential: The project offers an opportunity for cancer oriented translational research in a developing field of targeted therapy with real social and economic benefits. The research base offered by the project would furnish successful performances in translating results in practical medicine. European added value: The project contributes for enhancing visibility of European research excellence and translating research results for human health. Institution/University Name of Institution/University "Victor Babes" National Institute of Pathology Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Spl. Independentei 99-101 50096 Bucharest Pathology Research Team Research Team Name University Department of Pathology "Ljudevit Jurak" Individual Researcher No Research Team Leader Name MD Alma Dubravic Research Team Members Team Member 0 MD Ante Reljic [[email protected]] Team Member 1 B.Sc. Zlatko Papes [[email protected]] Team Member 2 MD Ivana Nola [[email protected]] Team Member 3 MD Zvonko Kejla [[email protected]] Team Member 4 B.Sc. Zdenka Silek-Saran [[email protected]] Team Member 5 MD Jaksa Filipovic-Cugura [[email protected]] Team Member 6 MD Tomislav Plasaj [[email protected]] Team Member 7 MD Josip Fajdic [[email protected]] Team Member 8 MD Jasna Talan-Hranilovic [[email protected]] Team Member 8 MD Ana Krvavica [[email protected]] Team Member 10 MD Monika Ulamec [[email protected]] Team Member 11 MD Marina Kos [[email protected]] Team Member 12 MD Drinko Balicevic [[email protected]] Team Member 13 MD Majda Vucic [[email protected]] Team Member 14 MD Davor Tomas [[email protected]] Team Member 15 MD Hrvoje Cupic [[email protected]] Team Member 16 MD Dora Brezovecki-Bidin [[email protected]] Team Member 17 MD Alma Dubravic [[email protected]] Team Member 18 MD Bozo Kruslin [[email protected]] Team Member 19 MD Mladen Belicza [[email protected]] Team Member 20 MD Marija Strnad [[email protected]] Research Team Projects Project Name Organization and evaluation of pathoanatomical tumour registry and tumour bank Project Leader MD Mladen Belicza [[email protected]] Project Funding Agency Ministry of Science, Education and Sports Project Budget 4055 € Project Start Date 0000-00-00 Project End Date 0000-00-00 Project Partners Project Summary Registries of different diseases, including tumors, play an impontant role in the epidemiology, followup of patients and evaluation of therapy, and represent a basis for scientific research. Evaluation of such registries showed many failures like inappropriate coding of diagnosis and tumor side and type leading to misinterpretation of data on the incidence, histologic type and behaviour of tumors. Technological advances enable investigation of the genome offering new perspectives for diagnosis and treatment. Such investigationes largely depend on adequacy of the material stored in tumor tissue banks. Pathologists with their expertise and responsibility for histopathologic diagnosis play a central role in collection of human tissues, in accordance with medical, legal and ethical standards, not only for diagnostic purposes, but also for research. The aim of this project is development and evaluation of the computer tumor registry of biopsy and autopsy data at the Deprtment of Pathology. Registry will contain crucial clinical and laboratory findings representing the source of data that could be used by National Registry of Cancer. We will analyse the incidence of tumors. The nomenclature, classification and coding of diagnoses will be performed according to the International Classification of the Diseases (MKB 10). In routine work we will use standard histologic, histochemical and Pathology immunohistochermical methods, and in situ hybridisation. Tissue samples embedded in paraffin will be stored during at least 10 years period representing the basis of tumor tissue bank. Certain tumors will be stored during longer period in deep freezer in liquid nitrogen. Computer-based data coded according to the MKB 10 will enable us to follow cancer patients and exchange data with other republic centres and other countries. Tissue tumor bank will provide a permanent source of samples for additional biomedical resarch. Project Website Contact Person Name MD Alma Dubravic Email [email protected] Function Research Assistant Phone +385 1 37 87 465 Fax +385 1 37 87 244 Website www.kbsm.hr/Jurak/ Research Team Objectives Main Fields Pathology Epidemiology Information Technology, Statistics, Documentation Development and evaluation of the computer tumor registry and autopsy data. Analysis of the incidence of some tumors, particulary of the breast, genitourinary, gastrointestinal, and central nervous system, thyroid gland, melanomas, and incidental tumors discovered at autopsy.Creating of tumor tissue bank. Partners/Interests researcher industrial partner Pathology Genetics Surgery Interests in improving computer-based data project, ideas on use of tumor tissue bank. Interest in scientific researching of tumor blood vessels, and similar topics conected to tumors behaviour. Research of changes in blood vessels that supply tumors, and their impact on tumor behaviour Institution/University Name of Institution/University University Department of Pathology "Ljudevit Jurak" Number of Employees 36 Number of Researchers 15 Country Croatia Postal Adress Vinogradska cesta 29 10000 Zagreb Pediatrics Research Team Research Team Name Department of Paediatrics Individual Researcher No Research Team Leader Name Mr. MD, PhD Alojz Gregoric Contact Person Name Mr. MD, PhD Alojz Gregoric Email [email protected] Function Professor of Paediatrics Phone +386 2 321 2416 Fax +686 2 331 2393 Website www.sb-mb.si Research Team Objectives Main Fields Pediatrics Partners/Interests researcher Suitable Paediatrics ANALYSIS OF CANDIDATE GENES FOR VESICO - URETERIC REFLUX Introduction. Primary vesicoureteric reflux (VUR) is a common urological anomaly in children with an approximate incidence of 1% in newborns. It is a disease of genetic origin and it shows a strong familial association. The VUR appears to be inherited in an autosomal dominant mode with reduced penetrance but candidate genes have not been described yet. Data from a genome wide linkage study and from studies on knock-out mice with VUR phenotype suggest that several other genes if mutated might cause the development of VUR independently. Such candidate genes causing VUR in mice are genes of angiotensin II receptor type 2 (AGTR2) and uroplakin 3 (UPK3). In addition, variable clinical presentations of the disease in affected families suggest that other genes might affect the penetrace of VUR. Single nucleotide polymorphisms such as C825T in the gene for G protein ©¬3 subunit (GNB3), L10P in the gene for transforming growt factor ©¬1 (TGFB1) and C2046T in the gene for the ¥á1 chain of collagen type 1 (COL1A1) have biological consequences and they could influence the development of VUR. Methods. DNA was extracted from venous blood from 85 patients diagnosed with VUR. Coding exons of genes AGTR2, UPK3 and UPK1B were screened using heteroduplex analysis and detected nucleotide variations were confirmed with sequencing. Polymorphisms C825T, L10P and C2046T were detected with the PCR-RFLP method. Results. A sequence variation changing asparagin to aspartic acid at the codon 137 (N137D) in exon 5 of the UPK1B gene was detected in 4.7% of patients with VUR and in 0.83% of controls (OR = 5.87, 95%Cl 1.54-22.33, p = 0. 017). Also an overrepresantation of 825T allele in the GNB3 gene was observed in patients when compared to the control group of healthy individuals (¥ö©÷ = 7.38, p = 0.025, df = 2). Conclusions. Our results implicated UPK1B gene in the development of VUR and the detected aminoacid substitution N137D might be a direct cause for the disease. Also the C825T polymorphism from the GNB3 gene might be involved in the development of the VUR, possibly as a genetic modifier. Genes AGTR2 and UPK3 as well as polymorphisms L10P from gene TGFB1 and C2046T from gene COL1A1 were not associated with the development of VUR in our sample of patients. At the moment we are collaborating in this research project with Medical Faculty Rijeka and Split, but we are interested to spread our research to other Medical Faculties of Medical Research Initiative South Eastern Europe. The aim of the study is to analise 300 - 500 children for candidate genes for VUR. Institution/University Name of Institution/University General Hospital Maribor Number of Employees 2400 Number of Researchers 33 Country Slovenia Postal Adress Ljubljanska 5 2000 Maribor Pediatrics Research Team Research Team Name Kalmanti Maria Stiakaki Eftichia Martimianaki Georgia Choumerianou Despina Individual Researcher No Research Team Leader Name Dr Helen Dimitriou Research Team Projects Project Name Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side. Project Leader Prof Christian Jorgensen [[email protected]] Project Funding Agency European Union Project Budget 4500000 € Project Start Date 2003-01-01 Project End Date 2007-12-31 Project Partners Project Website www. genostem.org Contact Person Name Dr Helen Dimitriou Email [email protected] Function Assistant Professor Phone +32810 394674 or +32810 394664 Fax +32810 394673 Website http// med uoc.gr Research Team Objectives Main Fields Paediatrics Biology Genetics Hemopoiesis in childhood malignancies · Tissue Culture and Stem cell assays · Bone Marrow Purging by PDT (Photodynamic treatment) · Evaluation of cord blood as a source of hematopoietic progenitors for transplantation, · Late effects of chemotherapy · Phase II/III clinical studies in pediatric malignancies · Stem cells from different sources (BM, PB, CB). Isolation, characterization and ex vivo expansion · Isolation, characterization, ex vivo expansion and in vitro differentiation of bone marrow mesenchymal stem cells · Oncogene expression and transformation potential of stem cells · Cell cycle study and immunophenotype of stem cells. · Study of apoptosis of stem cells. Partners/Interests researcher industrial partner Paediatrics Genetics Biology Experience in cell biology, molecular techniques, tissue culture techniques, animal model facilities Ex vivo expansionmolecular characterization differentiation, transformation potential of stem cells Hemopoiesis in childhood hematological disorders Effect of external stimuli on the apoptotic features of cells derived from bone marrow of children Late effects of chemotherapy on children treated for malignancies Photodynamic treatment for bone marrow purging Institution/University Name of Institution/University University of Crete , Medical School Number of Employees 800 Number of Researchers 600 Country Greece Postal Adress PO Box 2208 0 GR 71 Heraklion, Crete Pediatrics Research Team Research Team Name South-East Balkan Endemic Nephropathy Group (SEBENG) Individual Researcher No Research Team Leader Name Professor of pediatrics Amira Peco-Antic Research Team Members Team Member 0 MD, PhD Danica Bukvic [[email protected] ] Team Member 1 Marina Subasic [] Team Member 2 Assistent Danka Pokrajac-Milincic [] Team Member 3 Associated professor Velibor Tasic [] Team Member 4 Professor Marusia Lilova [] Team Member 5 Professor Jasmina Markovic-Lipkovski [] Team Member 6 MD Jelena Maletkovic [[email protected]] Team Member 7 PhD Ana Gligic [[email protected]] Team Member 8 MD Dusan Paripovic [[email protected]] Team Member 9 Professor Amira Peco-Antic [[email protected]] Contact Person Name Professor of pediatrics Amira Peco-Antic Email [email protected] Function Head of Nephrology department, University children Phone 381 11 2772 591 Fax 381 11 3612858 Website www.udk.bg.ac.yu/klinika/ Research Team Objectives Main Fields Paediatrics Public health services Genetics Progression and prevention of chronic kidney disease in children, hemmorhagic fever with renal involvment and Balkan endemic nephropathy. Partners/Interests researcher Genetics Clinical microbiology Paediatrics Pediatric and adult nephrologist who is involved in the medical care of patients suffering from Balkan endemic nephropathy and/or hemmorhagic fever with renal involvment and their pediatric relatives. Many chronic kidney diseases (CKD) which may lead to terminal renal failure in adults have beginning in childhood. Predictors of these diseases are only partially known and traditional risk factors such as hypertension, proteinuria and decreased glomerular filtration rate are in fact, the indicators of established renal damage. Therefore, the search for more sensitive risk markers continues. The present study is a prospective cohort study that will employ an extensive array of risk factors (epidemiological/environmental, genetic and clinical) that can explain genesis of Balkan endemic nephropathy (BEN). Epidemiological and environmental investigations will include isolation and characterisation of hantaviruses from the positive animals in endemic regions of BEN (rodent’s lung, antipodes and other wild and domestic animals) as well as in material (urine, blood) from the BEN patients and from the patients with hemorrhagic fever with renal involvement. Immune status on hantaviruses will be investigated in the BEN patients and in their healthy pediatric relatives. Genetic analysis will be focused on genes RET, GDNF and GFRA-1 which have the critical role in renal development as demonstrated in knockout mouse models and on the polymorphisms of the reninangiotensin system genes and polymorphisms of the most important detoxicating enzymes genes that may have a role in BEN development. Clinical part of this study will be concentrated on assessment of sensitive markers of CKD in the pediatric relatives of BEN patients. Therefore we will examine glomerular hyperfiltration that is a crucial event for progression of CKD. It will be estimated from the following: a renal functional reserve (RFR) that will be detected by measurement of the change in creatinine clearance following a meat-free protein meal in children pre-treated with cimetidin, Pediatrics quantitative and qualitative analyses of proteinuria (global, albumin, immunoglobulin G and SDS/PAGE) pre and after the test of physical exercise, and the maximal bipolar renal measurement done by real-time ultrasound scanning. To evaluate which antedates, loss of RFR and renal dysfunction or nondipper type of circadian rhythm of blood pressure (BP) the following examinations will be done: nocturnal and diurnal BP , nocturnal and diurnal natriuresis and proteinuria and the relationship of GFR and RFR with night/day rations of BP, urinary sodium and protein excretions. We hope that our investigation will show that genetic and epidemiological/environmental factors (viruses) have a role in development of BEN. If we prove that early signs of disease may be found in children and adolescents from endemic regions it will be very important for early start of renal protection. Institution/University Name of Institution/University University children's Hospital Number of Employees 150 Number of Researchers 10 Country Serbia and Montenegro Postal Adress Tirsova 10 11000 Belgrade Pediatrics Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Prof Senka Mesihović-Dinarević MD FESC Contact Person Name Prof Senka Mesihović-Dinarević MD FESC Email [email protected] Function Head of the Department of Paediatrics Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Paediatrics Partners/Interests RISK FACTORS FOR THE DEVELOPMENT OF ARTERIOSCLEROSIS IN PAEDIATRIC POPULATION Lipids are recognized as a significant risk factor in the development of atherosclerotic processes as well as hypertension. The appearance of clinical manifestations of atherosclerosis comes in unpredictable periods of life. The investigations which show the initial phase are mostly limited by the small number of nosological groups in different populations, so we aim to start the investigations on this topic in the South-East region of Europe. In childhood it is possible to study the pathological precursors of cardiovascular disease and risk factors which accelerate the development of the atherosclerotic process. The basic research of lipoproteins, apolipoprotein metabolisms, the biology of developing atheroma processes in the cell and the role of genetics in creating coronary artery disease are necessary in the field of preventive cardiology. The aim of this project would be to investigate the levels of serum lipoproteins and blood pressure in the paediatric population age 0 do 18 years with suspicion of cardiovascular disease, to evaluate the correlation between cardiovascular disease other than atherosclerosis and the appearance of dyslipoproteinaemia in this population. Patients and methods: the investigations should be carried out at University clinical Centre Sarajevo, Paediatric clinic, paediatric cardiology department and out patient’s clinic, during the period from 3 years as well as in the other European Paediatric clinic in the region mentioned above. It would include approximately 300 patients, age 0-18 years with control group. The criteria of the European Community would be used during random choice of patients and the conditions for including or excluding patients. Age groups should be formed as: I (0.30 days), II (1-12 months), III (1-4 years), IV (4-7 years), V ( 7-11 years), VI (11-14 years) and VII (14-18 years). The control group would be formed from healthy children in relation to age forming 4 subgroups: I (4-7 years), II (7-11 years), III (11-14 years) and IV (14-18 years). The patients who would be included should satisfy the following conditions: undisturbed carbohydrates metabolism, orderly functions of thyroid, kidneys and liver with suspicion of cardiovascular disease. The excluding criteria would be: presence of diabetes mellitus, hypothyroids, acute disease and reconvaleascency. The parameters in the investigations are planned to be objective: age, sex, height, weight, blood pressures measurements (including 24 -72 hrs monitoring), pulse, saturation of oxygen, ESR, FBC, urine, glucose level in blood, urine and creatinin levels, liver enzymes, alkali and acid phosphates, status of lipoproteins (total cholesterol, triglycerides, LDL cholesterol, LDH cholesterol, apoplipoproteins, ECG; EFCG, echocardiography; and subjective: history (personal and family), smoking, alcohol in the family, sport activities, practical works and length time spending in school, type of nutritional habits and calories of intake meals. Since nutritional intake could affect the status of lipoproteins in serum (during pregnancy, brest feeding input) so nutritional status of each patients should be noted. The expectations of this project are: to discover the pathological precursors of cardiovascular disease and risk factors which could influence the development of the atherosclerotic process in childhood which represents a wide spectrum of medical investigation, with the aim of delaying the development of atherosclerotic vascular lesions in the adult population. Pediatrics Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Pharmacology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD, PhD, MA Slobodan Jankovic Research Team Projects Project Name Pharmacological analysis of effects of biologically active substances on smooth muscles from gastrointestinal and urogenital tract. Project Leader Professor Slobodan Jankovic [[email protected]] Project Funding Agency Ministry of Science of Republic of Serbia Project Budget 50.000 € Project Start Date 2006-01-01 Project End Date 2011-12-31 Project Partners Project Summary Investigation of effects and mechanism of action of glutamate on isolated human ureter and rat colon. The effect is being tried on both spontaneous and electric field-stimulated contractions. Also, effects of antiepileptics on isolated Fallopian tubes are investigated. Project Website Contact Person Name MD, PhD, MA Slobodan Jankovic Email [email protected] Function Professor of pharmacology Phone +381641168103 Fax +38134370073 Website medf.kg.ac.yu Research Team Objectives Main Fields Pharmacology Therapeutics Effects of biologically active substances on tone and spontaneous contractions of isolated smooth muscle preparations, of both human and animal origine. Special interest in smooth muscles from human ureters, Fallopian tubes and gastrointestinal tract. Among the substancies studied are glutamate, antiepileptics, derivatives of cisplatin. The other fields of research are pharmacoepidemiology, pharmacovigilance and pharmacoeconomy. Partners/Interests researcher Pharmacology Pharmacologist or physiologist To investigate effects of antituberculotics on isolated human ureter and Fallopian tubes. Institution/University Name of Institution/University Medical Faculty, University of Kragujevac Number of Employees 210 Number of Researchers 50 Country Serbia and Montenegro Postal Adress Svetozara Markovica 69 34000 Kragujevac Pharmacology Research Team Research Team Name Department of Pharmacology / Medical Faculty of the University of Split / Croatia Individual Researcher No Research Team Leader Name Professor Mladen Boban Research Team Members Team Member 0 Professor Mladen Boban [[email protected]] Team Member 1 M.D. Jonatan Vukovic [[email protected]] Team Member 2 M.D. Ivana Mudnic (Music) [[email protected]] Team Member 3 M.S., M.D. Darko Modun [[email protected]] Team Member 4 M.D. Ivica Brizic [[email protected] ] Research Team Projects Project Name Extracorporeal heart preservation Project Leader Professor Mladen Boban [[email protected]] Project Funding Agency Ministry of Science, Republic of Croatia Project Budget 33000 € Project Start Date 2002-09-01 Project End Date 2006-06-01 Project Partners Slovenia / University of Ljubljana Faculty of Medicine / Institute of Pharmacology and Experimental Toxicology / Laboratory of Cardiovascular Research / Gorazd Drevensek (head) Project Summary The development of methods for prolonged preservation of donor hearts is one of the most important problems of cardiac transplantation. Cardioplegic arrest and hypothermic storage, the most common method of donor heart preservation during transport, does not provide adequate cardiac protection longer than few hours. If hearts could be preserved for at least 20 hours the pool of donor hearts would be increased, as would electivity of the operation, potential for tissue typing, and anonymity of donors. Numerous pharmacological interventions on improving extracorporeal heart preservation are directed toward: reduction of heart metabolic needs during isolation, cellular swelling, application of precursors for energy - rich intermediates, free radical scavengers, and coronary flow protectors. On the other side, it has been shown that moderate wine consumption, particularly red wine, provides beneficial effects on cardiovascular system and human health. It seems that antioxidants from the polyphenolic wine fraction play crucial role in that process. Some compounds from that group (catechin, quercetin, resveratrol) have been effective in protecting hearts after ischemia and hypoxia, inhibiting platelets aggregation, enhancing nitric oxide production, preventing low density lipoproteins oxidation… Hence, we will investigate protective effects of the standardized wine extract applied in vitro and as a pre-treatment in vivo, on heart and coronaries subjected to short and long - term hypothermic isolation. In order to achieve synergistic protective effects, the wine extract will be also combined with butanedione monoxime, a negative inotropic agent, which significant protective effects we have proved in these models. Protective effects on the isolated heart will be manifested as a better improvement of the contractility, coronary flow, oxygen consumption usefulness, electrophysiological stability, decreased biochemical markers of oxidative stress (lipid peroxides) and tissue injury (creatine kinase, lactate dehydrogenase and troponin), histological preservation and enhanced nitric oxide production. Wine extracts protective effects on the isolated coronary rings will be presented as stronger vasodilatation responses to endothelium dependent (acetilcholine) and independent (nitroprusside, pinacidil) vasodilators. This research is of relevance for many other conditions and procedures in cardiology and cardiosurgery, and is also stimulative for healthier feeding habits. Project Website Contact Person Name Professor Mladen Boban Email [email protected] Function Head of Department Phone +38521557904 Pharmacology Fax +38521465073 Website www.mefst.hr Research Team Objectives Main Fields Pharmacology Clinical chemistry Physiology Red wine, cardiovascular system, oxidative stress, polyphenolics, uric acid. Partners/Interests researcher industrial partner Pharmacology Clinical chemistry Physiology We are interested in research partners who are familiar with analytical methods for human biological samples, like LC MS analysis of plasma. Also we are looking forward to adopt new methods for evaluation of vascular parameters in humans, especially focusing on estimation of endothelial function. We are interested in industrial partners who will find their interest in this detailed study on mechanisms of bilogocal effects of wine and wine-derivate products. There is a great potential for production of new, improved, and biologically more potent wine products. Numerous studies have shown that moderate consumption of wine, especially red wine, has beneficial effects on cardiovascular system. These effects are mainly attributed to wine polyphenolics. Polyphenolic wine extracts and some polyphenolic compounds (resveratrol, catechin e.g.) are among others, associated with reduced susceptibility of LDL to oxidation, reduced platelets aggregation, increased production of nitric oxide (NO) and increase of human plasma antioxidant capacity. Recent studies have shown that polyphenolics are poorly absorbed and that their plasma concentrations are too low to explain some biological effects of wine. For instance, an elevation of plasma antioxidant capacity after red wine intake is significantly related to the acute elevation of plasma urates. Phenomenon of that urate elevation is polyphenolics-independent and its biological relevance is unknown. With this study, we want to separate the effects of wine polyphenolics from the effects of other wine constituents. Our aim is to determine in what extent the effects observed in in vitro biochemical measurements and isolated organ studies can be linked with the effects in humans after intake of tested wines and beverages based on that wines. Institution/University Name of Institution/University Medical Faculty of the University of Split Number of Employees 125 Number of Researchers 80 Country Croatia Postal Adress Soltanska 2 21000 Split Pharmacology Research Team Research Team Name Drug delivery group (formulation and delivery of conventional drug molecules and products of biotechnology) Individual Researcher No Research Team Leader Name professor Katerina Goracinova Research Team Members Team Member 0 professor katerina goracinova [[email protected]] Team Member 1 assistant professor renata raicki [[email protected]] Team Member 2 assistant to prof marija glavas [[email protected]] Team Member 3 PhD student maja simonoska [[email protected]] Team Member 4 PhD student nikola geskovski [[email protected]] Research Team Projects Project Name INFLUENCE OF BIOPOLYMER INTERACTIONS ON THE DRUG DELIVERY FROM CHITOSAN-ALGINATE COLLOIDAL CARRIER SYSTEMS Project Leader professor Katerina Goracinova (pharmacy group) [[email protected]] Project Funding Agency NATO Science for peace program Project Budget 150000 € Project Start Date 0000-00-00 Project End Date 0000-00-00 Project Partners Brian Amsden, Queen's University, Kingston, ON, Canada - NATO Country Project Director Macedonia Aleksandar Andonovski, Institute of Physics, Faculty of Natural Sciences and Mathematics, SS. Cyril and Methodious University, Skopje, Republic of Macedonia - Partner Country Project Director Physics group) Katerina Goracinova, Faculty of Pharmacy, SS. Cyril and Methodious University, Skopje, Republic of Macedonia - Partner Country Project Co-Director / Pharmacy group Project Summary Implementation of the knowledge in the development of the drug targeted biopolymer microparticulate carrier system was done, by which the improvement of the delivery and efficacy of incorporated drug and decreasing of adverse effects and toxicity was achieved. The technological process on small laboratory and larger-scale production of the well-defined biopolymer microparticles will be also established. The product designed is the mucoadhesive microparticulate polysaccharide drug carrier and polysaccharide based microspheres coated with enterosoluble material Project Website http://www.cs.org.mk/web/index.htm Project Name PREPARATION AND EVALUATION OF MICROPARTICLES FOR ORAL CONTROLLED DRUG DELIVERY Project Leader professor katerina goracinova [[email protected]] Project Funding Agency TUBITAK and Macedonian Ministry of science Project Budget 15000 € Project Start Date 2005-03-02 Project End Date 2008-03-02 Project Partners Professor Atila Hinchal, University of Haccettepe, Ankara, Turkey Professor Sema Calis/ University of Hacceteppe, Ankara, Turkey (co-director from Turkish side) Project Summary Intravenous administration of most drugs for colon cancer therapy produces severe systemic side effects due to their cytotoxic effect on normal cells. Development of site specific oral formulations for controlled colon-specific delivery would be a novel approach for increasing the drug efficacy and Pharmacology lowering the drug side effects. Also lectin mediated micro and nano particulate specific delivery can combine two functions in anticancer drug delivery systems, being targets to cancer cells and inducing anticancer effect because in tumor pathology aberrant glycosilation is a common attribute of neoplastic growth and lectins which selectively and reversibly bind to carbohydrate structures have demonstrated the ability to induce or control a number of metabolic and proliferative processes. Preparation, characterization of bioefficient highly specific controlled release DDS for delivery of different anticancer model substances to the colon will lead to efficient targeted anticancer therapy with lowering of toxic and side effects of the anticancer drugs. Project Website Project Name IMMOBILIZATION OF BIOACTIVE SUBSTANCES IN BIODEGRADABLE HYDROGELS OR FUNCTIONALIZED MICELLS; POSSIBLE APPLICATION AS BIOCATALYSTS OR DRUG RELEASE SYSTEMS Project Leader professor maja cvetkovska [[email protected]] Project Funding Agency Mac ministry of Science and BAN Project Budget 15000 € Project Start Date 0000-00-00 Project End Date 0000-00-00 Project Partners professor Hristo Cvetanov, Bulgarian Academy of Science professor Katerina Goracinova, Faculty of Pharmacy Project Summary incorporation of drug molecules in polymeric microparticulate systems for improving delivery and efficacy Project Website Contact Person Name professor Katerina Goracinova Email [email protected] Function head of the institute of pharm techn and biopharmacy Phone +38923126024 Fax +38923123054 Website www.cs.org.mk/web/index.htm ; www.ukim.edu.mk Research Team Objectives Main Fields Pharmacy Therapeutics Other allied sciences Research team main fields are within the scope of formulation science, dosage form design and evaluation, targeted delivery, mucoadhesive drug delivery, absorption enhancement. The main areas of drug delivery problem solving are: 1. Formulation ofn Controlled and Targeted drug delivery systems 2. Application of New Biomaterials as colloidal drug carriers- microspheres, nanospheres, liposomes 3. Alternative routes of application of peptides and proteins and their optimal stability and activity 4. Evaluation of Drug/polymer, protein/polymer interactions The group mission is scientific research in drug delivery with emphasis on efficaceous treatment (targeted and controlled delivery)/ and or prevention of diseases Partners/Interests researcher industrial partner research partner Pharmacy drug delivery of conventional drug molecules and products of biotechnology Institution/University Name of Institution/University Faculty of Pharmacy; Univ Sts Cyril and Methody Number of Employees 40 Number of Researchers 20 Country Macedonia Pharmacology Postal Adress Vodnjanska 17 1000 Skopje Pharmacology Research Team Research Team Name Pharmacology Individual Researcher No Research Team Leader Name Mrs., PhD Irena Mlinarić-Rašćan Contact Person Name Mrs., PhD Irena Mlinariè-Rašèan Email [email protected] Function Asist. Professor of Pharmacology Phone + 386 1 47 69 645 Fax +386 (0)1 425 80 31 Website http://www.ffa.uni-lj.si/index.php/eng/content/view/full/43 Research Team Objectives Main Fields Pharmacology Partners/Interests researcher industrial partner Suitable Pharmacology 1. INNOVATIVE DRUGS –TARGETING MOLECULAR BASIS OF CELL DEATH.APOPTOSIS Serine proteases have been shown to actively participate in the process of apoptosis in mammalian cells. The oustanding example is Bortezomib (Velcade®), a reversible inhibitor of the chymotrypsin-like activity of the proteasome that has been recently approved for treatment of multiple myeloma. Our previous studies revealed two distinct roles for serine proteases in apoptotic process. Firstly, we have shown that inhibition of anti-apoptotic serine proteases governs the onset of the caspase-dependant apoptotic cascade. Secondly, we have also demonstrated the involvement of a serine protease in the terminal stage of apoptosis by showing that chymotrypsin–like protease activity is required for internucleosomal DNA fragmentation in apoptotic cells. The overall goal of the proposed study is to further elucidate the role of serine proteases in molecular mechanisms underlying apoptotic cell demise, particularly in oligonucleosomal DNA cleavage. We aimed to address these issues by two parallel strategies. Firstly, we intend to use a direct pharmacogenomic approach to screen newly synthesized serine protease inhibitors for the potency to induce apoptosis in the absence of internucleosomal DNA laddering. We are further to use newly-identified inhibitor as a bait to isolate the interacting molecule, which followed by N-terminal sequencing and cloning of responsible gene shall lead to the identification of a key molecule. Simultaneously, a reverse pharmacogenomic approach shall be applied in which selected recombinant serine proteases will be tested for inhibition with selected inhibitors. Both approaches shall converge at the stage of identification of a serine protease whose inhibition leads to the desired phenotype, namely to induce caspase dependent apoptosis and/or interfere with DNA oligonucleosomal laddering. Further functional studies shall include over-expression and down-regulation of the newly identified gene, in order to prove the hypothesis. 2. PHARMACOGENTICS: TIOPURINE PHARMACOGENETICS from bench to bedside Thiopurine pharmacogenomics is the study of how an individual’s genetic inheritance affects the body’s responses to drugs. The application of pharmacogenomics in the individualized drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide costeffective pharmaceutical care. Objective of proposed project encompasses from bench to bedside concept, emphasizing the need of basic research application in the current clinical practice. The project will be conducted by interdisciplinary team including a pediatric oncologist, molecular geneticists and a clinical biochemist and will provide novel concepts for application in the clinic as well as the importance of linking the first-hand clinical experiences to problem-solving oriented research. We aim to obtain three levels of knowledge and implement them in daily clinical practice: (1) Genetic characterization of the patient’s drug profile. Application of the diagnostics based TPMT polymorphisms and HPLC enzyme activity analysis, developed in our laboratory. (2) Establishment of novel diagnostic tests by the identification and characterization of other candidate genes, or by using a genome scale non-candidate approach. (3) Understanding of the molecular mode of action of thiopurines and the metabolism of key enzymes. Proposed study will contribute to the further development of pharmacogenomics, a field of study that combines the knowledge emerging from the Human genome project with classical pharmaceutical disciplines. By implementing the proposed project we also contribute to common European research area and mobility of researchers. Pharmacology Institution/University Name of Institution/University Faculty of pharmacy Number of Employees 113 Number of Researchers 60 Country Slovenia Postal Adress Askerceva 7 1000 Ljubljana Pharmacology Research Team Research Team Name Pharmacology Individual Researcher No Research Team Leader Name Professor Milica Prostran Research Team Members Team Member 0 Professor Marina Stojanov [[email protected]] Team Member 1 Associate Professor Branislava Miljkovic [[email protected]] Team Member 2 Research Associate Zorica Nesic [[email protected]] Team Member 3 Research Associate Nevena Divac [[email protected]] Team Member 4 Research Associate Radan Stojanovic [[email protected]] Team Member 5 Associate Professor Sonja Vuckovic [[email protected]] Team Member 6 Associate Professor Zoran Todorovic [[email protected]] Team Member 7 Professor Milena Pokrajac [[email protected]] Team Member 8 Professor Ranka Samardzic [[email protected]] Team Member 9 Professor Milica Prostran [[email protected]] Team Member 10 Research Assistant Katarina Vucicevic [[email protected]] Team Member 11 Senior Res. Fellow Eleonora Dzoljic [[email protected]] Team Member 12 Research Assistant Marija Petronijevic [[email protected]] Contact Person Name Professor Milica Prostran Email [email protected] Function Chair of Postgraduate Study in Pharmacology Phone +381-11-2684363 Fax +381-11-2686025 Website med.bg.ac.yu Research Team Objectives Main Fields Pharmacology Internal Medicine Neurology Our investigation deals with the modulation of action of inflammatory mediators (e.g. NO, ROS etc.) in experimental models (e.g. ischemia-reperfusion injury, pain or muscle contractility), as well as in clinical settings (e.g. ARF or ACS), including the pharmacokinetics of drugs with antiinflammatory actions. Partners/Interests researcher Pharmacology Internal Medicine Neurology - Basic Medicine reseachers (pathology and biochemistry of inflammation) - Clinicians (neurology, cardiology, nephrology) Our project will deal with the modulation of action of inflammatory mediators (e.g. NO, ROS etc.) in three different experimental models: a) ischemia-reperfusion injury; b) pain; and c) muscle contractility a) Renal ischemia and reperfusion (I/R) may cause both apoptotic and necrotic renal cell death leading to acute renal failure (ARF). Pharmacological interventions against ARF, successful in animal models, have proven to be largely negative in clinical conditions and did not decrease a high mortality in such patients. Novel therapeutic approach to ARF should involve modulation of proinflammatory network of events that lead to apoptosis and/or necrosis of kidney cells via activation of NFkappaB. Acute pretreatment with statins (e.g. simvastatin, pravastatin, atorvastatin etc.) have protected myocardium and/or kidney in certain models of I/R injury, the mechanism(s) of such action remaining to be established. Rat I/R injury in vivo model would be used for the Pharmacology investigation of the acute protective effects of statins, and the following parameters would be analyzed: MAP, HR, histopathological score including immunohistochemistry, and selected biochemical parameters (serum and urine electrolytes, transaminases, and creatinine clearance, i.e. parameters of glomerular and tubular function). The model used was established in collaboration with the WHRI, London, UK (e.g. Chatterjee et al. 2004; 2005). b) Evaluation of the antinociceptive and antiinfammatory effects, as well as effects on the body temperature and other behavioural effects (i.e. catalepsy, righting reflex, ataxy, etc.) of opioid analgesics (fentanyl and its novel analogues synthesised on the Faculty of Chemistry, Belgrade), antiepileptics (carbamazepine, oxcarbazepine and its active metabolite, monohydroxy derivative-MHD and gabapentin), nonsteroidal anti-inflammatory drugs used in human and veterinary medicine (flunixin meglumine, indomethacin), antidepressants (amitriptyline, etc), as well as psychodelic agents (e.g. phencyclidine) in experimental animals (adult rats, neonatal rats and adult mice) is planned. We are planning to evaluate the sites (central and/or peripheral) and mechanisms of drugs action (the involvement of adrenergic, adenosine, opioidergic, gabaergic receptors, the inhibition of the enzymes cyclooxigenase, and a role of L-arginine-NO system), as well as drug-drug interactions - antagonism and synergism (both pharmacodynamic and pharmacokinetic). Several animal models of acute and chronic pain (inflammatory, postoperative, visceral and neuropathic pain) will be used, and mechanical, thermal and chemical pain stimuli will be applied. c) Reactive oxygen and nitrogen species (ROS and RNS, respectively) are known to modulate contractility of both skeletal and cardiac muscle. ROS and RNS are generated under various pathological and physiological conditions (e.g. shock, respiratory failure, fatigue etc.). Different modulators of NO system (NOS inhibitors, L-arginine, BH4), as well as other drugs influencing inflammatory network (e.g. statins, antiepileptics etc.), will be tested in well established experimental models regarding skeletal and/or heart muscle contractility. d) Also, a separate series of investigations will be dedicated to pharmacoepidemiology/pharmacovigilance of antiinflammatory drugs in clinical and outpatient settings (e.g. statins, NSAIL etc.). Finally, a separate series of investigations will include pharmacokinetics of centrally acting drugs which may modulate inflammatory status (e.g. carbamazepine and certain antidepressants). Research goal Taking into account the presented subject, description and importance of the research (experimental models a-c, as well as pharmacoepidemiological and pharmacokinetic analysis), the possible research goals will be the following: a) improvement of glomerular and tubular function in rats subjected to I/R injury after acute pretreatment with the statins, as well as the development of the appropriate subacute model of such injury for further investigation; b)evaluation of sites (central and/or peripheral) and mechanisms of drug action, as well as drug-drug interactions-antagonism and synergism (both pharmacodynamic and pharmacokinetic) in order to improve pharmacotherapy of pain, especially neuropathic pain; c) evaluation of possible improvement of respiratory and cardiac muscle failure. In addition, pharmacoepidemiological as well as pharmacokinetic studies would help to re-establish principles of rational pharmacotherapy of certain painful-inflammatory conditions. Institution/University Name of Institution/University School of Medicine, University of Belgrade Number of Employees 7481 Number of Researchers 7481 Country Serbia and Montenegro Postal Adress Dr Subotica-starijeg 1 11129 Belgrade Physiology Research Team Research Team Name Department of Neuroscience, Split, Croatia Individual Researcher No Research Team Leader Name MD, PhD; Prof. Zoran Dogas Research Team Members Team Member 0 MD Zeljka Roje [[email protected]] Team Member 1 MD Zavisa Colovic [] Team Member 2 MD, MSc Mladen Carev [[email protected]] Team Member 3 MD, PhD; Prof. Goran Racic [[email protected]] Team Member 4 MD, MSc Nenad Karanovic [[email protected]] Team Member 5 MD Suzana Mladinov [[email protected]] Team Member 6 BSc, Psychology; MSc Goran Kardum [[email protected]] Team Member 7 MD Renata Pecotic [[email protected]] Team Member 8 MD, PhD Maja Valic [[email protected]] Team Member 9 MD Nikola Poljak [] Research Team Projects Project Name Neurotransmitters in the control of breathing Project Leader Prof. Zoran Dogas [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-01-01 Project End Date 2006-12-01 Project Partners Project Summary Breathing is a complex behavior which requires the coordinated activity of several muscle groups and which must be precisely regulated by the brain via respiratory neurons to control arterial blood gases and acid-base status within the narrow limits compatible with life. The main objective of the study is to demonstrate the importance of roles of GABAergic, glutamatergic and serotoninergic receptors in the process of neurotransmission-regulated action of premotor respiratory neurons, as well as possible effects of the drugs acting at those receptors on sleep breathing disorders. We expect that microinjection of GABAA antagonist bicuculline in the vicinity of the respiratory neuron will modulate its discharge rate pattern as it was described in dogs, and has not been proven in rats (TonkovicCapin, 2001) and also that microinjection of GABAA channel blocker picrotoxin results in qualitatively different effects (blocking of inhibition during inactive phase of neuronal activity vs. gain modulation, Ðogaš et al., 1998). All of this would imply the complicated pharmacological regulation of GABA neurotransmission and complex role of that neurotransmission in the modulation and control of motor behavior during breathing. We do not expect that the gain modulation is modulated via the benzodiazepine site which would suggest that the effects of activation of benzodiazepine site, as a part of GABA receptor complex, are separated from the effects of GABA receptors in the control of respiratory neurons. Thus, one can expect that benzodiazepine drugs do not effect the sleep disordered breathing, and research on glutamate and serotonin drugs will demonstrate their roles. Studying the control of breathing requires an intact brainstem and spinal cord circuitry together with afferent input from the lungs. There is insufficient information about the central neural circuitry underlying the reflex control of breathing to generate mathematical or computer models as substitutes for animal experiments. Tissue culture experiments can not replicate the neural connections required for the production of breathing. The only way to conduct investigation about complicated function such as breathing is to use a whole animal model. This research may provide information that will be helpful in understanding the neuronal control of breathing and pharmacological treatment of patients with sleep disordered breathing such as opstructive sleep apnea or prevention of sudden infant death syndrom. Project Website http://zprojekti.mzos.hr/zprojektiold/result Physiology Contact Person Name MD, PhD; Prof. Zoran Dogas Email [email protected] Function Vice Dean; Dept. of Neuroscience, Chair Phone +385 21 557 905 Fax +385 21 557 955 Website http://www2.mefst.hr/default.asp?ID=38 Research Team Objectives Main Fields Physiology Anaesthesiology Otorhinolaryngology Research team is involved in studies on respiratory control during wakefulness, anesthesia and sleep. Basic research performed on rats includes electrophysiology, microejection techniques, neuropharmacology, and neuronal recordings from the respiratory related brain stem neurons. Human studies are mainly done on breathing disorders during sleep (e.g., sleep apnea), as well as on cognition and sleep. Partners/Interests researcher industrial partner Neurology Psychiatry Public health services sleep diagnostics and therapy Sleep disorders Institution/University Name of Institution/University University of Split School of Medicine Number of Employees 1500 Number of Researchers 1000 Country Croatia Postal Adress Soltanska 2 21000 Split Physiology Research Team Research Team Name Laboratory for the physiology of circulation Individual Researcher No Research Team Leader Name MD, PhD Ines Drenjancevic-Peric Research Team Members Team Member 0 MD, PhD Ines Drenjancevic-Peric [[email protected]] Team Member 1 MD Mario Gros [[email protected]] Contact Person Name MD, PhD Ines Drenjancevic-Peric Email [email protected] Function Vice Dean for Science School of Medicine University of Osijek Phone +385 31 512 882 Fax +385 31 512 833 Website www.mefos.hr Research Team Objectives Main Fields Physiology Immunology and Immunohaematology Control mechanisms of the blood flow through the tissue, functional and structural adaptation of microcirculation (resistant arteries and arterioles), genetic factors in the development of hypertension, interaction of various signalling systems in the cell and their common denominator which regulates cell function (endothelial and vascular smooth muscle cell) and function of blood vessels in response to different stimuli; the effect of physiological regulators of vascular function (vasodilators and vasoconstrictors, oxygen and mediators of arachidonic acid), role of the reninangiotensin system in the control of vascular reactivity, dysfunction of the blood vessels in diabetes mellitus and other microangiopathy, inflammation, aterosclerosis and sepsis, physiological mechanisms of hyperbaric oxygen treatment Partners/Interests researcher industrial partner Physiology laboratory of physiology, experience in vascular physiology, functional and genetic analysis, mollecular biology techniques role of oxygen in vascular control in health and disease Institution/University Name of Institution/University School of Medicine University J. J. Strossmayer Osijek Number of Employees 300 Number of Researchers 120 Country Croatia Postal Adress J. Huttlera 4 31000 Osijek Physiology Research Team Research Team Name Neurophysiology Unit Individual Researcher No Research Team Leader Name Dr Andrea Cavaggioni Research Team Members Team Member 0 Dr Carla Mucignat [[email protected]] Team Member 1 Dr Michela Bondi [michela.bondi@unipd.] Team Member 2 Dr Alessandro Rubini [[email protected]] Contact Person Name Dr Andrea Cavaggioni Email [email protected] Function Full professor Phone 0039 049 827 5314 Fax 0039 049 827 5301 Website unipd.it Research Team Objectives Main Fields Physiology Neurophysiology of olfaction Glioblastoma experimental model Partners/Interests researcher Physiology Endothelium physiology and pathology Effect of cytokines in endothelium conditioning Institution/University Name of Institution/University University of Padova Number of Employees 6000 Number of Researchers 4000 Country Italy Postal Adress Via 8 Febbraio 6 35130 Padova Physiology Research Team Research Team Name Physical Medicine and Rehabilitation Individual Researcher No Research Team Leader Name Mr. MD, PhD, Zmago Turk Contact Person Name Mr. MD, PhD, Zmago Turk Email [email protected] Function Asist. Prof. of Physical Medicine and Rehabilitation Phone + 386 2 234 56 01 Fax + 386 2 23 45 600 Website www.mf.uni-mb.si Research Team Objectives Main Fields Physiology Physiology Partners/Interests researcher industrial partner Suitable Physiology POSSIBILITIES FOR COLLABORATIVE RESEARCH IN THE FIELD OF PHYSICAL THERAPY IN COOPERATION WITH ASSOCIATED UNIVERSITIES COORDINATED BY MEDICAL UNIVERSITY OF GRAZ Taking into consideration the rapid aging of Europe's population (24%) as well as in Republic of Slovenia (20%) and other former Yugoslav republics (18 to 20%) it seems necessary to concentrate our research efforts on medical fields of geriatrics and gerontology. Therefore we propose the following projects/studies in the field of geriatrics: • Founding of centers for gerontology as a project for complete nursing of the elderly, from domestic to institutional health care service. • Particularities of hospitalization of the elderly. Analysis of specialities of hospitalization of elderly patients, means of rehabilitation after injuries as a complete medical treatment. • Comparative analysis of life of the elderly in nursing homes and founding of day health care services. Concerning the field of gerontology we are currently researching nutrition and recreation habits of the elderly as well as ergonomic obstacles. Other projects that can be carried out in the field of Physical and Rehabilitation Medicine: a) Influence of low-frequency magnetic fields on human health (4 research projects already completed) b) Influence of therapeutic electromagnetic fields on diseases of human locomotor system and their treatment c) Thermal imaging of the human locomotor system – assessment of inflammations, temperature variations and consequent diagnosis of diseases d) Treatment and prolonged rehabilitation of patients with severe head traumas and diseases. CONCLUSION We see the possibilities for our research in the fields of gerontology and geriatrics, integral treatment and rehabilitation of human locomotor system, environmental influences on human health (especially from an ergonomics point of view), physical therapy. Our research team consists of: prof. of Physical Medicine and Rehabilitation, 3 teaching assistants, 4 doctoral candidates and a research assistant (in the field of computer science). We offer the aforementioned research projects on behalf of Faculty of Medicine, University of Maribor. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Physiology Research Team Research Team Name Physiology Individual Researcher No Research Team Leader Name Mr. PhD Marjan Rupnik Contact Person Name Mr. PhD Marjan Rupnik Email [email protected] Function Professor of Physiology Phone +386 2 330 5854 Fax +386 2 330 5853 Website http://www.mf.uni-mb.si/fizio/rupnik.html Research Team Objectives Main Fields Physiology Partners/Interests researcher industrial partner Suitable Physiology 1. FUNCTION OF ENDOCRINE CELLS IN DISEASE AND COMPENSATORY PROCESSES Our main expertises are electrophysiology (patch-clamp) and optophysiology (wide-field, confocal and twophoton microscopy) on living endocrine tissue slices. The endocrine tissue slice preparation was due to its complexity rarely used tool to study endocrine function. We have recently established a novel preparation to study the endocrine function in pancreas, its endocrine part being vital for the control of the blood glucose and its dysfunction being critical in severe diseases, like diabetes mellitus. Our preparation is the first, where the hormone (e.g. insulin) release and electrical activity can be checked in the intact tissue environment with a single cell resolution and where important cellular characteristics, like ion channels and metabolic activity can be assessed together with the secretory competence. We expect that the use of genetically modified animals and animals which develop sickness due to planned inbreeding will give us key information of the defects causing an endocrine disease and help us develop new methods of treatment and diagnostics. We propose a research project to define the molecular basis of type-2 diabetes mellitus or similar endocrine disorders. By applying measurements of secretory competence, electrical activity and metabolism in endocrine cells in tissue slices by a combination of electro- and optophysiology in whole pancreas slices we are willing to cooperate in characterization of putative secretory machinery dysfunction and compensatory processes in endocrine tissues due to specific genetic manipulations. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Physiology Research Team Research Team Name Prevention of obesity and cardiovascular risk factors in children Individual Researcher Yes Research Team Leader Name Prof. dr. Mirjana Pavlović Research Team Projects Project Name Capacity Development in Nutrition in Central and Eastern Europe Project Leader Mirjana Pavlovic, MD, PhD, RPHNutr. Contact Person Name Mirjana Pavlovic, MD, PhD, RPHNutr. Email [email protected] Function Associate Research Professor, CEE Network Coordinator Phone +381 24 548398 / +381 11 303 1997 Fax +381 24 548398 / +381 11 303 1997 Website www.imi.bg.ac.org Research Team Objectives Main Fields Physiology Cardiovascular risk factors Obesity Nutrition Atherosclerosis Primary prevention Many reports review the evidence that the precursors of atherosclerosis begin in childhood. The majority of risk factors are connected with eating habits and life style patterns already adopted in childhood and youth. Overweight in childhood has been associated with increased risks of hypertension, adverse lipid profiles, type II diabetes, and early atherosclerosis lesions, as well as increased risks of adult obesity and obesity related morbidities and mortality in adulthood. The correlation between risk factors level found in early youth and their later values is the most important fact for primary prevention CVD in childhood. The project includes primary prevention program of CVD risk factors integrated in paediatric care of children. It implies both high risk and population based approaches. At the population level recommendations will be linked with advice to implementing the Step 1 Diet low in saturated fat and cholesterol for all children over 2 years of age, with promotion of healthy nutrition and lifestyle and physical activity programs in preschool childcare centres and schools. Participation of the whole society is important. Individual level involves assessment and early identification of the children with obesity, hypertension, sedentary lifestyle and family history for selective screening of lipid parameters in the course of routine health care. It would be important also to identify positive aspects to be used in intervention. According to observed risk factors on individual level the recommendations are based on promotion of physical activity and nutritionally adequate diets with balanced intake of calories, vitamins and minerals, this as a Step 2 Diet with further reduction in cholesterol and saturated fat with nutrition professional consultation. Primary prevention in childhood can be more efficient and cost effective in preventing CVD than in adulthood. The project includes continuous longitudinal growth status monitoring by anthropometry, of child obesity through various ages at individual level. It will also imply identifying hypertension, registering type of lifestyle (including physical activity, and smoking of parents etc.), family history of health and disease, selective screening of biochemical parameters (lipids mainly) in the course of routine health care. Individuals will also get professional advice on how to change lifestyle based on recommendations on physical activity and nutritionally adequate diets with balanced intake of calories, vitamins and minerals, including reduction in intake of saturated fat. At the population level recommendations will be linked with advice impacting on lifestyle, also including physical activity promotion programs in preschool childcare centres and schools. Participation of the whole society is important. Here the aim is to change nutrition and lifestyle in whole populations over 2 year, including dietary quality of families, by for example providing examples of nutritionally adequate diets. It may also entail assessing nutritional quality of menus, Physiology education in healthy nutrition of children, parents, cooks, teachers and other actors in the society. This can be done by using mass-media, engage in celebrations of the World Food Day which takes place every October, and take the opportunity of other ongoing programmes such as National Month of Healthy Nutrition for preschool and schoolchildren. The plan will include assessing the quality of diet; this will be compared to the nutritional needs of individuals, diet consulting counselling (including individualised menus) and counselling on healthy lifestyle. Adequate software will be developed in addition to already available softwares. For using the data from monitoring and evaluation appropriate software applications for data analysis at the individual and population level is needed. Adequate software will be developed in addition to already available sofwares. Towards the end of the project a number of tools for local and national use will be developed. That may include: • • • Integrate primary prevention program of CVD risk factors into pediatric care of children, implying two complementary approaches, "individual-high risk strategy" and a "population based - health promotion strategy". Establish a model for primary prevention program of cardiovascular diseases in a regional/national strategy for primary prevention of the risk factors causing chronic noncommunicable diseases, primarily cardiovascular, complying with the WHO “Global Strategy on Diet, Physical Activity and Health“. The project will focus on implementation of a prevention programme, and emphasise dissemination results in the selected communities, but also share information with other countries in a establishe Network for Capacity Development in Nutrition in CEE. • • Framework for nutrition education program in curricula ("Health promoting schools"). Broad plans/frameworks for action and suggestions for optimal meals for children in kindergartens and schools, in cooperation with the food producers (for example: a milk based product for each child and fruit and vegetable as snacks in every school). • Improving the quality and the choice of the meals in school canteens "Healthy school canteens". • Raise the issue of responsible marketing of foods, snacks and soft drinks for children. • During the implementation of this project are planning cooperation with relevant State ministries (health, education and sport, agriculture, science and environment), food industrySMEs, municipalities, media, consumer associations, NGO-s, and the private sectors, with the aim of initiating a process towards a ’’National Nutrition Action Plan’’ according to the principles developed by the WHO Regional Office for Europe. Throughout the project community participation will be actively promoted. That implies engaging the whole community in promoting healthy lifestyles and adequate nutrition (such as in campaigns, festivals, workshops, seminars, lectures and public education through the media, press conferences, Internet communication, video films and brochures). Partners/Interests researcher Cardiovascular risk factors Obesity Nutrition Atherosclerosis Primary prevention Objectives: 1. Integrate primary prevention program of CVD risk factors into paediatric care of children, implying two complementary approaches, "individual-high risk strategy" and a "population based - health promotion strategy". 2. Establish a model/framework for primary prevention program of cardiovascular diseases in a regional/national strategy for primary prevention of the risk factors causing chronic noncommunicable diseases, primarily cardiovascular, complying with the WHO “Global Strategy on Diet, Physical Activity and Health“. 3. Monitoring of the nutritional status in children for early detection of the risk factors for cardiovascular diseases (obesity, hypertension, hyperlipidemia, positive family history and inadequate dietary intake and physical activity). 4. Establish a national database on cardiovascular risk factors, dietary patterns and quality, nutritional status (measured by anthropometry) and level of physical activity in children. 5. Create a process for developing regional/national and local strategies and food and nutrition policies, complying with the “Nutrition Action Plan” for Europe by WHO. Expected results The project will focus on implementation of a prevention programme, emphasising dissemination of Physiology results from assessments to the communities involved. However, sharing information with other countries in a established Network for Capacity Development in Nutrition in CEE would be important. In shorter term the project will monitor nutritional status of children in order discover early overweight and obesity, and the nutritional risk factors on individual and/or at population level for preventing obesity and cardiovascular risk factors, and for health promotion activities. In the long term the expected result is to reduce overweight, obesity and cardiovascular risk factors, and an improved nutritionally quality of diets, and increased physical activity in children assessed against the criteria of the WHO Global Strategy on Diet, Physical Activity and Health. Institution/University Name of Institution/University Department of Nutrition and Metabolism, Institute for Medical Research, University of Belgrade Number of Employees Number of Researchers Country Serbia Postal Adress Tadeusa Koscuskog 1, PO Box 102 11000 Belgrade Physiology Research Team Research Team Name Individual Researcher No Research Team Leader Name Prof. Dr. Barbara Obermayer-Pietsch Contact Person Name Prof. Dr. Barbara Obermayer-Pietsch Email [email protected] Function ass. Prof. Phone +43 316 385 2934 Fax +43 316 385 3428 Website http://www.meduni-graz.at/endo-nuklearmedizin Research Team Objectives Main Fields Physiology gender-based medicine Partners/Interests gender-based medicine Institution/University Name of Institution/University Clinical Department for Endocrinology and Nuclear Medicine, Medical University of Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 15 8036 Graz Psychiatry Research Team Research Team Name Molecular and biochemical markers of psychiatryc disorders Individual Researcher No Research Team Leader Name MD PhD Dalibor Karlovic Research Team Members Team Member 0 MD Marko Martinac [[email protected]] Research Team Projects Project Name Analize of serum lipids in psychiatryc disorders Project Leader MD PhD Dalibor Karloviæ [[email protected]] Project Funding Agency Project Budget € Project Start Date 2001-11-11 Project End Date 2006-03-11 Project Partners Project Summary Project Website Contact Person Name MD PhD Dalibor Karloviæ Email [email protected] Function Psychiatryst, reearcher Phone +38513787345 Fax +38513787345 Website [email protected] Research Team Objectives Main Fields Psychiatry Pharmacology Clinical chemistry Main interest in psychopharmacology, clinical laboratory data in psychiatry (especialy lipids metabolism, endocrinology and molecular diagnostics) Partners/Interests researcher Psychiatry Polimorphisms of variety genes in schizophrenia, bipolar disorder and depression Institution/University Name of Institution/University University Hospital "Sestre milosrdnice", Dept. of Psychiatry Number of Employees 10 Number of Researchers 5 Country Croatia Postal Adress Vinogradska cesta 29 10000 Zagreb Psychiatry Research Team Research Team Name TELEMEDICINE & TELEPSYCHIATRY AMDA INTERNATIONALAMDA RS BA Individual Researcher No Research Team Leader Name Prof dr sc med Milan Stojakovic Research Team Members Team Member 0 Dr sc Zoran Mavija [[email protected]] Team Member 1 Mr sc Ozren Kordic [[email protected]] Team Member 2 Prof Dr sc med Zdravko Maric [[email protected]] Contact Person Name Prof dr sc med Milan Stojakovic Email [email protected] Function president Phone ++387 51 302 864 Fax ++387 51 302 864 Website home.blic.net/misos Research Team Objectives Main Fields Psychiatry Internal Medicine Information Technology, Statistics, Documentation RESEARCH ACTIVITIES:TELEMEDICINE.. E-health,mental health, telepsychiatry,e/mail psychoconsalting,forensic psychiatry Partners/Interests researcher industrial partner Information Technology, Statistics, Documentation Psychiatry Public health services DESCRIPTION OF REQUESTED PARTNER PROFILE: EXPECT interest for implementation of TELEMEDICINE.. & interest for implementation of telepsychiatry services in Bosnia. TELEMEDICINE & telepsychiatry Institution/University Name of Institution/University AMDA international /BA Number of Employees 5 Number of Researchers 3 Country Bosnia and Herzegovina Postal Adress K PETRA PRVOG 115 115 78000 home.blic.net/misos Public Health Services Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD Aleksandar Dzakula Contact Person Name MD Aleksandar Dzakula Email [email protected] Function Research Fellow Phone +385 91 582 88 92 Fax +385 1 4590 275 Website www.snz.hr Research Team Objectives Main Fields Public health services Social medicine Epidemiology Organization of helath care services; health care policy; health care management Partners/Interests researcher Public health services Social medicine Epidemiology Able to analyze health care sector and willing to manage internationla projects Rationalizing the hospital sector - policy driven research Institution/University Name of Institution/University University of Zagreb - Andrija Stampar School of Public Health Number of Employees 70 Number of Researchers 50 Country Croatia Postal Adress Rockefellerova 4 10000 Zagreb Public Health Services Research Team Research Team Name Individual Researcher Yes Research Team Leader Name senior analyst Marilena Ianculescu Research Team Projects Project Name Informational Centre of Dermathology Project Leader senior analyst Marilena Ianculescu [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-15 Project End Date 2008-12-15 Project Partners "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania Project Summary The web-based system will become an efficient tool for promoting good health and a healthy lifestyle, it will facilitate the co-operation between doctor and patient. Expected results: • a web-based modern system for informing citizens in the dermatovenereology domain having as central point a relational databases system; • an efficient and multifunctional tool for dissemination of the the dermatovenereology domain; • increasing the accessibility degree of the quality information regarding health and prophylaxis; • libraries with primary medical information and medical publications; • monitoring, educational and evaluation applications. Project Website www.cid.ro Project Name A Complex Integrated System for Health Education and Disease Prevention Project Leader Prof. dr. eng. mat. Adriana Alexandru [[email protected]] Project Funding Agency Project Budget € Project Start Date 2005-10-03 Project End Date 2005-09-30 Project Partners "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania Valahia University, Targoviste, Romania S.C. Software ITC S.A. Net Clip S.R.L. Project Summary The proposed project, due to its tackled approach, finds a place among the thematic fields S/T of CEEX 2005, aiming to improve the capacity of preventing diseases, to facilitate an early diagnosis and to realize health information space for knowledge discovery. Maintaining a state of good health for the population, adopting a healthier lifestyle, with special implications on long term in social and economic plan, can be made with the help of a sanitary culture, and information technologies are an extraordinary means to promote education in the public health domain. Making a complex integrated system like this one is a shared responsibility that implies cooperation and creating partnership among decision-makers in the health domain, health professionals and computer specialists. The proposed system will contain information organized in an relational database system about immunization, screening, prophylaxis strategies and methods, risk factors, occupational health, environmental factors, institutions in the public health field, educational models for different kinds of communities, a library with medical information and publications, and applications made to facilitate the dissemination of the analysis from the territory and the collaboration among the institutions having a role to play in the public health system (experience exchange, training, partnership proposals, promoting national and international programmes in the public health domain). Project Website www.edusan.ro Contact Person Name Marilena Ianculescu Email [email protected] Function senior analyst Public Health Services Phone +40-744 777967 Fax +40-21-224 11 21 Website www.ici.ro Research Team Objectives Main Fields Public health services Information Technology, Statistics, Documentation Advanced information technologies for the information society - networks and data base systems in public health domain Integrated solutions for public services for Health care e-Business Partners/Interests industrial partner Public health services Information Technology, Statistics, Documentation public health services IT Public health education using IT. Institution/University Name of Institution/University National Research Institute for R&D in Informatics Number of Employees 215 Number of Researchers 124 Country Romania Postal Adress Bd. Maresal Averescu 8-10 01145 Bucharest Public Health Services Research Team Research Team Name Individual Researcher Yes Research Team Leader Name PhD Ljiljana Tasic Research Team Projects Project Name Healt promotion and dessisses prevention of women health Project Leader professor Ljiljana Tasic [[email protected]] Project Funding Agency Pfizer, farmalogist, Shering Project Budget 14.000 € Project Start Date 2006-04-01 Project End Date 2007-03-31 Project Partners Faculty of Pharmacy, department of social pharmacy and Public Pharmacy Institution of Belgrade Project Summary healt promotion in three women population group (young, meadle and old); educate health providers (pharmacist and doctors) for the skills of health promotion and health life stiles changes; prevent sexual, cardiovasular, depression and osteoporosis in population of women in Belgrade -urban and rural area; create web and net platform and partnership with patients, public, media, and health professionals Project Website ww.zdravljezena.org Contact Person Name PhD Ljiljana Tasic Email [email protected] Function profesor Phone +381113970379 Fax +381113974349 Website www.pharmacy.bg.ac.yu Research Team Objectives Main Fields Public health services Information Technology, Statistics, Documentation Pharmacy qualty of health care; pharmaceutical care; pharmacoepidemiology and pharmacoeconomy; drug policy; e-health; e-pharmacy Partners/Interests researcher Information Technology, Statistics, Documentation Pharmacy Public health services experience in public health and drug policy, drug database and e-health improvement of health and drug public information sources Institution/University Name of Institution/University University of Belgrade,Facultz of Pharmacy Number of Employees 151 Number of Researchers 266 Country Serbia and Montenegro Postal Adress V.Stepe 450 11221 Belgrade Public Health Services Research Team Research Team Name Electronic patient records throughout Europe Individual Researcher No Research Team Leader Name Diana Szedlacsek Contact Person Name Diana Szedlacsek Email [email protected] Phone +40 21 22 835 Fax +40 21 22 835 Research Team Objectives Main Fields Public health services Information Technology, Statistics, Documentation electronic health recordings training of medical doctors European patient care Partners/Interests researcher Public health services Information Technology, Statistics, Documentation The purpose of the project aims at: Educating the medical staff in the new member and associate candidate countries, with the trends for electronic patient records already emerging in some of the EU states. Performing the first steps towards the analysis of the state-of-the-art in this extreme fragmented domain and towards the unification of electronic registration systems already existing throughout Europe – at least at a first administrative step. The expected results are: 1. Increased willingness of the medical staff to cooperate not only throughout regional areas, but throughout the whole European domain. 2. Increased ease to consult patients throughout Europe. 3. Increased efficiency of the administrative (financial, IST, recording) aspects of the medical care. Impact: Throughout Europe, the problem of electronic patient records is analyzed and steps are performed slowly enough. Therefore, unification of the efforts in this respect is sought to have a tremendous impact upon the unified European medical care system. The interests and points of views of the medical doctors are still restrained to personal and national level. Through the unification of the recording systems, a wider view is sought for the medical doctors. Contribution to the EU or regional policy: The proposed project aims at meeting social needs and catalyze the delivery of European/Regional policy objective(s), by generalizing the electronic recording of patients, by easing the patient care throughout Europe and by training the medical doctors in using such generalized systems for patient care. European research potential: Due to numerous attempts to introduce and generalize an electronic patient recording system, it is to be inferred that the unification of research efforts throughout Europe – and especially in the new member and in the associate candidate countries -, is going to mobilize a strong potential for disseminating and converting the results into social and economical benefits. Since only partial recording systems exist and since they are not by all means interusable throughout Europe, it is also clear that the proposed project aims at building on past and current investments and successes – at least at national level – successes which should be materialized into a European widespread such system. European added value: Since such generalized patient recording systems are sought to be used throughout Europe, it is also obvious that the project considers additional public funding to be justified by the externalities and wider benefits from the research and by the need to attract increased public and private investments. Also, the need for cooperation between medical, IST, accounting, administrative staff involved in medical care ensures multidisciplinarity and critical mass of scale and scope. The projects, as it was presented above aims to overcome fragmentation and unnecessary duplication, lack of connections and of interoperability; to complement other intergovernmental, national and private actions; to address European level problems. Institution/University Name of Institution/University SME Bio-Consult service s.r.l. Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Sos. Stefan cel Mare 14 20141 Bucharest Public Health Services Research Team Research Team Name Traditional medical prevention and care throughout Europe Individual Researcher No Research Team Leader Name Diana Szedlacsek Contact Person Name Diana Szedlacsek Email [email protected] Function Phone +40 21 22 835 Fax +40 21 22 835 Website Research Team Objectives Main Fields Public health services Social medicine Partners/Interests researcher Public health services Social medicine The objectives of the present proposal are: To build on existing European empirical, traditional medical practices, in order to obtain an efficient system for preventing and combating different types of diseases (including major ones). To ease the dissemination of healthcare empirical (national or regional) knowledge systems in order to increase public awareness regarding the necessity to get more involved into personal and societal medical care. To increase the opportunities for rediscovering traditional, European values in the medical field. To widen the research connected to such traditional experience in the medical practices, in order to enlarge both medical and public experience in preventing and combating diseases, as well as to gain new, richer insights into the health sciences. Expected results: Increased public awareness regarding the necessity for self-care Eased European and national budgets from unnecessary medical costs, where traditional remedies might do Widened views in the health sciences research and medical practice fields Widened consciousness of public and medical staff regarding a common European tradition in the medical practice Increased research into European traditional practices in the health sciences Translation of national and regional topics in the field of healthcare Impact: At European level: increased efficiency of both traditional and classical systems for medical care, improved public and medical consciousness related to traditional valuable practices, widened experience in health research topics (through widened views), improved European specific conscious about own values. At regional levels: same as above, plus increased satisfaction towards promotion of regional values in health care and sciences. At national level: same as above, plus widened insight into the European practices, applicable at national levels. At personal level: increased conscience of the European citizenship and of a wider European practice in self-care, increased self-esteem as European citizen and improved health status through use of specific, European (therefore, better physiologically adapted) care systems. Contribution to the EU or regional policy: The EU policy aims at a dynamic and competitive knowledge-based economy, which is to be reached through the present project – in the health care sector, through obtaining new remedies and practices destined to improved health, through lowering the burden of classical healthcare by using traditional, non-conventional, cheap and at-hand practices, products and self-care systems. This view is currently gaining more and more importance throughout the world and the US and Asian countries have already made serious progresses in this direction. Due to the above, the aim of sustainable economic growth is also to be reached through the application of the results of the project. Since the European/regional policies aim at generating both a European high-quality, specific value intended to the global exchanges, the present project fits to such objective. Also, the increased awareness about the traditional practices in healthcare aims at boosting the European research into new, valuable directions, already undertaken, for example, by Asian countries in their own directions. European research potential: As concerns the views from the research community and industry, mention should be made from the fact that the international market is increasingly invaded by North-American products and Asian traditional remedies and practices, which already form nowadays a coherent system, even if they are (slightly) divided into more main directions. Therefore, European specific remedies not only might improve the health status of Europeans (through the use of specific remedies, adapted to physiologically specific needs), but will boost the research and industry into this emerging domain of the global market. Past investments are already successful in this field, at Public Health Services regional levels and this experience should be shared among European countries in view of its generalization. Research in this direction is only emerging in Europe, and serious efforts should be made in order to encompass the advance of other countries and regions, though success in the field can already be witnessed in Europe. Yet, a stronger impulse must be conveyed to the area, in order to increase the potential for excellent research and technological development and for disseminating and converting the results into social and economic benefits. European added value: Current public support for tradition in general and for traditional remedies and practices in particular, is continuously increasing, and a best approach would be to meet the increasing needs of the public for knowledge in this field, by offering sound, correct research-supported data at all necessary levels. It is obvious that both public and private investments are duly justified in a field where European research and market are slightly backwards – as compared with other regions and states. Also, such an approach will offer the opportunity for European centers of excellence through collaborative research, needed for the high-throughput requested by the field. Such a research domain will require the necessary multidisciplinarity and critical mass, due to the fact that, at present, such remedies and practices are widely known at national or regional level at most, not at the European level. The involvement of European research in the above-mentioned direction will enhance visibility of European research excellence, taking into account the current international trends and efforts. Institution/University Name of Institution/University SME Bio-Consult service s.r.l. Number of Employees n.a. Number of Researchers n.a. Country Romania Postal Adress Sos. Stefan cel Mare 14 20141 Bucharest Radiology Research Team Research Team Name Magnetic Resonance Research Department Individual Researcher No Research Team Leader Name MD Nicolae Bolog Research Team Members Team Member 0 MD Nicolae Bolog [[email protected]] Team Member 1 MD Irinel Oancea [[email protected]] Team Member 2 MD Angelica Mangrau [[email protected]] Team Member 3 Physicist Claudiu Ungureanu [[email protected]] Contact Person Name MD Nicolae Bolog Email [email protected] Function Head of Radiology and Magnetic Resonance Department Phone +40 21 5992300 / 304 Fax +40 21 5992308 / 304 Website www.ehmri.ro Research Team Objectives Main Fields Radiology Information Technology, Statistics, Documentation Clinical Research in Magnetic Resonance Imaging focused on abdominal and musculoskeletal imaging, and soft-tissue tumors Partners/Interests researcher Radiology Information Technology, Statistics, Documentation special interest in development of new MR technology such as MR elastography and in development of new contrast agents for MR imaging. Clinical Research in Magnetic Resonance Imaging focused on abdominal and musculoskeletal imaging and soft-tissue tumors Institution/University Name of Institution/University Emergency Hospital Bucharest Number of Employees 2707 Number of Researchers 87 Country Romania Postal Adress Calea Floreasca 8 01446 Bucharest Radiology Research Team Research Team Name Individual Researcher No Research Team Leader Name Prof.dr Lidija LINCEDER Research Team Members Team Member 0 Dr sci. Nermina OBRALIĆ Team Member 1 Dr sci. Šerif BEŠLIĆ Team Member 2 Mr .sci. dr Nermina KANTARDŽIĆ Team Member 3 Dr. sci. Hiba BAŠIĆ Team Member 4 Mr. sci. dr Amela MORNJAKOVIĆ Team Member 5 Dr Sabina PREVLJAK Team Member 6 Vegar S. Team Member 7 Dr Sabina PREVLJAK Team Member 8 Dr. sci. Semir BEŠLIJA Team Member 9 Sefic I. Team Member 10 Mirela Kalamujic Contact Person Name Prof.dr Lidija LINCEDER Email [email protected] Function Head of the Institute of Radiology and Onkology Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Radiology MRI super paramagnetic iron oxide lymphangiography oncology Partners/Interests Evaluation of MRI lymphangiography in diagnostic of oncology patients (Super paramagnetic Iron Oxide enhanced MRI lymphangiography) Background: Status of regional lymph nodes has important significance for therapy and prognosis of newly diagnosed cancers. The presence of nodal metastases determinates therapeutic options and it is crucial to have this information to make decision about therapy. Further more nodal metastases indicates worse prognosis, and thus is important in follow up of oncology patients. Current imaging modalities rely mostly on size and morphologies of the lymph nodes. Metastases can be present in non enlarged nodes, and not all enlarged nodes are malignant. Super paramagnetic Iron Oxide enhanced MRI can overcome some of limitations in the existing imaging modalities and provide much needed staging information before the therapy and in the follow up of the cancer patients Aim: To evaluate characterization of lymph nodes in native MRI lymphangiography versus super paramagnetic iron oxide enhanced MRI lymphangiography in diagnostic of the oncology patients. Materials: The patients with histology of malignant tumors will undertake MRI imaging before and 24 hours after receiving optimal dose of super paramagnetic iron oxide. Vital signs, serum and urine levels and eventual adverse events will be monitored. Qualitative nodal architecture, size and signal intensity changes will be assessed in T1-, T2-, and T2* weighted images in native and enchanted MRI. The MR imaging super paramagnetic iron oxide appears to be effective for characterization of lymph nodes in patient with various primary tumors and it will be very important to check significance and sensibility of this new imaging method. Radiology Institution/University Name of Institution/University Medical Faculty of Sarajevo, University of Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Radiology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Dr. Manuela Aschauer Contact Person Name Dr. Manuela Aschauer Email [email protected] Function Phone +43 316 385 3850 Fax Website http://www.meduni-graz.at/radiologie/ Research Team Objectives Main Fields Radiology Partners/Interests Analysis of MR study data and/or joint studies in the field of MRA Institution/University Name of Institution/University Department of Radiology, Medical University of Graz Number of Employees Number of Researchers Country Austria Postal Adress 8063 Graz, Auenbruggerplatz 9 8036 Graz, Tel. Radiology Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Univ.-Prof. Dr.med.univ. Franz Ebner Contact Person Name Prof. Franz Ebner Email [email protected] Function Phone +43 316 385 3271 Fax Website http://www.meduni-graz.at/radiologie/ Research Team Objectives Main Fields Radiology Partners/Interests High-Field MR – experimental or preclinical work with volunteers Institution/University Name of Institution/University Department of Radiology, Medical University of Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 9 8036 Graz Social Medicine Research Team Research Team Name Individual Researcher Yes Research Team Leader Name MD, MSc, PhD, specialist of pediatrics Aida Mujkic Contact Person Name MD, MSc, PhD, specialist of pediatrics Aida Mujkic Email [email protected] Function Assistant professor Phone +38514554959 Fax +38514566777 Website www.snz.hr Research Team Objectives Main Fields Social medicine Paediatrics Public health services The field of social pediatrics which means all the influences on child's health (public health aspect of family planning, child growth and development, nutrition,social relations towards children, special interest for child injury prevention) Partners/Interests researcher industrial partner Paediatrics Social medicine Public health services The researcher: experience in the scientific research and analysing data The industrial partner: motivation to invent new or change curent products to fulfill safety requirements The public health project for parents of preschool chidren with the aim to educate them about injury prevention and safety promotion. Institution/University Name of Institution/University Zagreb University-School of medicine-A. Stampar SPH Number of Employees 100 Number of Researchers 40 Country Croatia Postal Adress Rockefellerova 4 10000 Zagreb Surgery Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Professor, MD, PhD Gojko Buljat Contact Person Name Professor, MD, PhD Gojko Buljat Email [email protected] Function Head, University Hospital of Traumatology Zagreb Phone +385 1 46 10 363 Fax +385 1 46 10 365 Website www.trauma.hr Research Team Objectives Main Fields Surgery Anatomy Neurology spinal injuries and diseases spinal surgery Partners/Interests researcher industrial partner Surgery Radiology Therapeutics experince with algorithms and national registers adequate computer programs/databases spinal injuries and diseases - diagnostic and treatment algorithms Institution/University Name of Institution/University University Hospital of Traumatology Zagreb Number of Employees 452 Number of Researchers 18 Country Croatia Postal Adress Draskoviceva 19 10000 Zagreb Surgery Research Team Research Team Name Individual Researcher No Research Team Leader Name Dozent Darko Anticevic Research Team Members Team Member 0 MD PhD Tomislav Djapic [[email protected]] Team Member 1 MD Marko Bergovec [[email protected]] Team Member 2 MD Bostjan Baebler [] Team Member 3 MD PhD Professor Ingeborg Barisic [[email protected]] Team Member 4 PhD biol. Professor Biserka Nagy [[email protected]] Team Member 5 PhD biol. Inga Marijanovic [[email protected]] Team Member 6 MDPhD Professor Slobodan Vukicevic [[email protected]] Team Member 7 PhD Lovorka Grgurevic [[email protected]] Contact Person Name Dozent Darko Anticevic Email [email protected] Function pedaitric ortohopedic surgeon, staff member Phone 481-9911 Fax 2303-119 Website www.mef.hr Research Team Objectives Main Fields Surgery Genetics Paediatrics Paediatric orthopaedic rare bone and joint diseases; Osteogenesis imperfecta; Skeletal Dysplasias; Bone regeneration Partners/Interests researcher Genetics Paediatrics Surgery with research and clinical experience with osteogenesis imperfecta Expression of gene for typ I collagen in patients with osteogenesis imperfecta Genomic and proteomic analysis of biomarkers in biological fluids of rare bone diseases Institution/University Name of Institution/University Dept Ortho Surg (Ped Ortho Unit), School of Medicine, ZagUniv Number of Employees 700 Number of Researchers 380 Country Croatia Postal Adress Salata 3 10000 Zagreb Surgery Research Team Research Team Name Department of Abdominal Surgery I Lymphatic Mapping and Sentinel Node Biopsy in Digestive System Neoplasms Individual Researcher No Research Team Leader Name Doc. dr. sc. Matija Horzic Research Team Members Team Member 0 Mr. sc. Mario Kopljar [[email protected]] Team Member 1 Doc. dr. sc. Leonardo Patrlj [] Team Member 2 Mr. sc. Kristijan Cupurdija [] Team Member 3 Dr Djana Vanjak-Bielen [] Team Member 4 Dr. Domagoj Vergles [] Team Member 5 Dr. Zeljko Lackovic [] Contact Person Name Mr. sc. Mario Kopljar Email [email protected] Function Surgery Phone +385 91 582 7446 Fax +385 1 290 3624 Website www.kbd.hr Research Team Objectives Main Fields Surgery Anatomy Genetics Malignant diseases of the digestive system represent important medical, social and especially public health issue in Croatia and in almost all countries of the Western civilization. Their most important feature is high mortality and morbidity of certain types of cancer, which is determined mostly by the quick dissemination of the primary tumor. Malignant tumors of the digestive system are among the most common malignant diseases in general, and the incidence of certain digestive tract cancers is increasing. Broadening of the general knowledge about the growth and dissemination of malignant tumors of the digestive system represents the basis for their successful surgical treatment. Since surgery is successful only in the early stages of cancer development, and mortality and morbidity caused by these tumors and their treatment represent significant medical and social problem, the research of growth and dissemination of the cancers of the digestive tract are today of great significance. This planned research therefore aims to broadening the knowledge of routes of spreading of the digestive tract tumors by intraoperative detection of tumor-infiltrated lymph nodes in order to enable the removal of potential lymphatic dissemination and therefore increase the radicality of surgical treatment. Curative treatment of solid malignancies is possible only by surgical resection of the primary tumor and the removal of all potential routes of lymphatic spread. The most common site of metastases from the tumors of the digestive tract are lymph nodes. Due to rich lymphatic drainage of the digestive tract, there is a large number of routes of lymphatic spread from tumors emerging in digestive tract. Since the knowledge about these routes of lymphatic drainage is mandatory for achieving adequate surgical radicality, precise intraoperative determination of lymph node infiltration and routes of lymphatic spread enable focused extension of lymphadenectomy to those areas that are not included in the standard range of lymphadenectomy, thus significantly increasing surgical radicality. Also, in the later stage of research, intraoperative detection of lymphatic flow from the primary tumor may lead to sparing those areas where no lymphatic spread from the primary tumor was observed. Results of this research should increase the number or truly radical resections, that should be made evident through the decrease in recurrence rates and increase in overall and disease free survival. Partners/Interests researcher Surgery Surgery Institution/University Name of Institution/University University Hospital Dubrava Number of Employees n.a. Number of Researchers Na.a Country Croatia Postal Adress Av. G. Suska 6 10000 Zagreb Surgery Research Team Research Team Name Department of Abdominal Surgery I - Quality of life measures in surgery Individual Researcher No Research Team Leader Name Doc. dr. sc. Matija Horzic Research Team Members Team Member 0 Dr. Domagoj Vergles [] Team Member 1 Dr. Zeljko Lackovic [] Team Member 2 Dr. Djana Vanjak-Bielen [] Team Member 3 Mr. sc. Kristijan Cupurdija [] Team Member 4 Doc. dr. sc. Leonardo Patrlj [] Team Member 5 Mr. sc. Mario Kopljar [[email protected]] Contact Person Name Mr. sc. Mario Kopljar Email [email protected] Function Surgery Phone +385 91 582 7446 Fax +385 1 290 3624 Website www.kbd.hr Research Team Objectives Main Fields Surgery Public health services Social medicine Disease itself, as well as surgical treatment of disease significantly changes the quantity and quality of life. However, the influence of various diseases and surgical treatment options on the quality of life remains insufficiently known, especially the impact on three dimensions of the quality of life: physical, social and psychological health. Analysis of retrieved data will enable the impact of various diseases and therapeutic options on all three dimensions of the quality of life, not only the quantity of physical health, and therefore improve the treatment and speed up the recovery. The question of quality of life is getting more attention in clinical research, as well as in everyday clinical practice. This is especially related to investigations in surgery, where the number of published papers in this field has increased 20-fold in the last twenty years. The goal of the research of the quality of life is primarily introductions mechanisms and standards for verifications of success of surgical treatment, and also definition of those dimensions of quality of life that is most influenced by surgical therapy, in order to enable targeted interventions for their improvement. Also, the analysis of the answers of treated patients on standard quality of life questionaires will be used to develop new questionaires, specially adjusted for particular subgroups of patients. The purpose of this research is improving the quality of health care, especially in the field of surgery. Monitoring quality of life of operated patients during treatment and in postoperative period will enable timely recognition of those patients that will benefit most from changing therapeutic procedures, resulting in afirmation of new procedures and methods of surgical treatment in addition to improving those already present. The results of this research will be used for improving the quality of surgical treatment of patients. Disease itself, as well as surgical treatment of the disease substantially changes the quantity and quality of health. Today, however, the influence of various diseases and treatment options on the quality of life remains vague, especially the effect on the three major constinuents of health: physical, social and psychological health. Analysis of retrieved data will enable determination of the influence of various diseases and therapeutic procedures on all three dimensions of the quality of life, and not only on the quantity of physical health, and therefore improve the treatment process and fasten the recovery of patients after surgery and reintegration in normal life in the community. Partners/Interests researcher Surgery Surgery Institution/University Name of Institution/University University Hospital Dubrava Number of Employees n.a. Number of Researchers n.a. Country Croatia Postal Adress Av. G. Suska 6 10000 Zagreb Surgery Research Team Research Team Name Department of abdominal surgery, Clinical Hospital Dubrava, Zagreb Individual Researcher No Research Team Leader Name Professor, MD, PhD Igor Stipancic Research Team Members Team Member 0 Professor Fiorella Biasi [] Team Member 1 MD, B.Sc. Gordana Kaic [[email protected]] Team Member 2 MD, PhD Dusko Kardum [[email protected]] Team Member 3 MD, PhD Andelko Korusic [[email protected]] Team Member 4 MD Milka Ozegovic [] Team Member 5 Sci. ad., PhD Marija Poljak - Blazi [[email protected]] Team Member 6 As. Prof. MD, PhD Zeljko Busic [[email protected]] Team Member 7 MD, PhD Drazen Servis [[email protected]] Team Member 8 MD Valentina Ratkajec [[email protected]] Research Team Projects Project Name Surgical and oxidative stress in colorectal malignancies Project Leader Professor, MD, PhD Igor Stipancic [[email protected]] Project Funding Agency Ministry of science, Republic of Croatia Project Budget 15000 € Project Start Date 2002-08-22 Project End Date 2006-05-31 Project Partners Croatia / Clinical Hospital Dubrava/ Department of abdominal surgery Croatia / Clinical Hospital Dubrava/ Surgical biomedical research lab Croatia / Ruder Boskovic Institute/ Department for Molecular Medicine Oxidative Croatia / Ruder Boskovic Institute/Laboratory for Oxidative Stress Austria / Institute fir Molecular Medicine, Biochemistry and Microbiology in Graz Italy / Institute for Biological and Medical Research in Torino Project Summary Cancer is an illness of continuos oxidative stress, while surgery represents acute local and systemic oxidative stress. Thus, beside is direct medical usefulness, surgery induces stress response that might promote or inhibit growth of possibly remaining cancer cells. This involves plays essential role also inβactivity of cytokines among which TGF colon carcinogenesis. Hence, interference of surgical stress involving cytokine network and activity of HNE, "second messenger of free radicals", would be of high importance for the outcome. Project evaluated basic and clinical aspects of surgery in colon malignancies that might improve monitoring patients' recovery and/or possible recurrence of disease and reflect on additional therapies. Surgical injury is associated with increased production of reactive oxygen species and utilization of antioxidant defense systems. Many experimental data are in support of a damaging role of excess of oxidative reactions, also termed oxidative stress, in systemic stress responses after surgical injury. Our findings obtained in previous project "Markers of systemic surgical stress response" have shown that even laparotomic cholecistectomy can induce systemic stress response that involves oxidative stress as well. Moreover, we have found that in rats surgical oxidative stress differs between healthy and tumor bearing animals, in particular in the presence of HO˙ radicals in blood . During oxidative stress lipid peroxidation occurs which leads to production of reactive aldehydes, among which 4-hydroxynoneal is denoted as “second messenger of free radicals” which also acts as a growth modifying factor for various types of cells including human carcinoma cells . Growth modifying effects of HNE seem to be mediated through c-fos activity and interfere with the effects of cytokines. Thus, HNE acts as a bifunctional growth factor that can stimulate growth of cells, but also suppress it or even induce programmed cell death (apoptosis) . Among cytokines relevant for the effects of HNE is TGF ß1, in particular for colon carcinomas. The TGF-beta´s are a family of cytokines with antiproliferative activity on many cell types. TGFß1 can stimulate proliferation of mesenchymal cells while stimulating the death of certain epithelial cells. This cytokine plays an important role in the colon epithelium, not only in the inhibition of cell proliferation, but also in the regulation of apoptosis. Escape from TGFß1-induced inhibition of proliferation has been observed in Surgery many tumor cells and may contribute to loss of growth control. In adenocarcinoma biopsies, susceptibility to lipid peroxidation processes and TGFß1 expression are below the control. Similarly, the adducts of HNE with proteins were significantly lower than controls in the plasma from cancer patients and significantly higher in the plasma from patients with Crohn‘s disease, often regarded to as precancerous. These findings suggest the existence of an association between oxidative damage and TGFß1 expression in human intestine, both in case of inflammation and in carcinogenesis. While monoclonal antibodies specific for HNE revealed the presence of HNE-adducts mostly in tumor stroma, we also found that TGFß1 inhibits the growth of human CaCo-2 and HT-29 colon cancer cells, and this cytokine’s action appears to be affected by HNE. Finally, our preliminary findings show that TGFß1 causes apoptosis in CaCo-2 cells. We evaluated growth features of cultured human adenocarcinoma and benign tumors (primary cultures) in respect to their sensitivity to HNE and TGFß1 on one side, and on another monitor parameters of systemic oxidative status in operated patients to define parameters suitable for improved monitoring of their stress response and convalescence. Project Website www.mzos.hr Project Name The role of neutrophils and oxidative stress in colorectal surgery Project Leader Professor, MD, PhD Igor Stipancic [[email protected]] Project Funding Agency Ministry of science, Republic of Croatia Project Budget 10000 € Project Start Date 2007-01-02 Project End Date 2011-01-02 Project Partners Croatia / Clinical Hospital Dubrava/ Department of abdominal surgery Croatia / Clinical Hospital Dubrava/ Surgical biomedical research lab Croatia / Ruder Boskovic Institute/ Department for Molecular Medicine Oxidative Croatia / Ruder Boskovic Institute/Laboratory for Oxidative Stress Italy / Institute for Biological and Medical Research in Torino Project Summary Surgical treatments induce local and systemic changes that involve neuroendocrine and the immune system functions. Such surgical stress is associated with oxidative stress. Progress in minimal invasive surgery, in particular laparoscopic surgery, is supported by clinical advantages in comparison to open surgery and by assumption of lower intensity of surgical stress in thus operated patients. In previous studies we described that even moderate surgical treatments, such as cholecystectomy, may induce generalized, i.e. systemic stress response. This includes oxidative stress, which is less pronounced in case of laparoscopy. It is certain that surgical removal of colorectal carcinomas causes more severe stress for patients, not only because of the higher extent of surgery but also because cancer itself causes oxidative stress. Inflammation, which accumulates iron, may have important impact on the iron metabolism in these patients in particular in case of metastases. It remains to be evaluated whether inflammation represents epiphenomenon of malignancy or a factor of cancer progression, in particular because iron acts as pro-oxidant, which can together with reactive oxygen species produced by inflammatory cells cause oxidative stress. Hence, controlling inflammation could influence tumor development. Because neutrophils are the most abundant immune cells involved in inflammation that produce mediators of oxidative stress (products of lipid peroxidation) thus influencing the growth of other cells and inducing their death, we will study their effects in respect to the type of surgical treatment of patients with colorectal carcinoma. Our current preclinical studies indicate that neutrophils have anti-cancer effects in the early stage of tumor development based on their oxidative burst and consequential oxidative stress. If in patients with colorectal carcinoma functional activity of inflammatory cells is altered before surgery due to cancer caused immune suppression, while surgery is followed by further change of the overall immune reactivity, it is an open question how do we influence inflammatory response to cancer (functional activity of neutrophils) in patients operated for colorectal carcinomas by open or by laparoscopic surgery? Our hypothesis is that this is important factor that influences recovery of patients, disease progression and the overall outcome. Project Website www.mzos.hr Contact Person Name Professor Igor Stipancic Email [email protected] Function Abdominal surgeon Surgery Phone +3851 290 3612 Fax +2851 290 3626 Website www.kbd.hr Research Team Objectives Main Fields Surgery Biochemistry Other allied sciences laparoscopic colorectal surgery; minimal invasive surgery; colorectal cancer; surgical stress; oxidative stress; inflammatory response; granulocytes Partners/Interests researcher industrial partner Surgery Biochemistry Other allied sciences Academic partners willing to collaborate in a regional and subregional international research project in the field of colorectal cancer. We look for researchers which field of work is chemiluminiscence, iron metabolism, oxidative stress, tumor cell lines, cytology and immunohistochemistry. We plan to include colorectal cancer patients in this project. Only the patients that voluntarily sign their consent, after being thoroughly informed about the project, will be included. After standardized preoperative preparation, the patients will undergo surgery. The type of colon resection will be primarily determined depending on cancer localization and stage, in order to fully meet the oncologic principles of the resection. If oncologically possible, the patients will choose between laparoscopic or open colon resection. All the patients will be operated by the project leader, to minimize treatment variability. The operation, as well as anesthesiological procedures, will be maximally standardized. The length of operation will be recorded, and later correlated with other findings. After the operation, postoperative care will be carried out in intensive care unit, if necessary. During postoperative hospital stay, all non-standard event, such as wound infection, elevated body temperature or other signs of systemic infection, postoperative bleeding or anastomosis dehiscence, will be recorded, and later correlated with other results. We will collect blood samples for every patient at 4 times: preoperatively, 24 hours, 7 days and 28 days after the operation. Blood samples will be collected from a peripheral vein, using Vacutainer system (Becton Dickinson, Plymouth, U.K.). Two vials containing EDTA will be collected for blood cell analysis, and two vials without anticoagulant will be collected for serum analysis. The collected blood will be used for measuring: complete blood count, neutrophil / lymphocyte ratio, standard biochemical parameters (serum protein and albumin level, liver transaminases, CRP, transferin, ferritin, bilirubin and other) using routine tests. Peripheral blood neutrophil activity will be measured using chemiluminescence. From the peripheral blood, lymphocytes will be separated by spinning blood samples in density gradient. They will be labeled using monoclonal antibodies and analyzed using flow cytometer, in order to determine CD4+ / CD8+ T cell ratio. Finally, serum will be separated from blood samples, aliquoted in 5 plastic vials and stored at –80°C. From these samples, we will later determine oxidative stress parameters using photochemical and immunochemical methods at Rudjer Boskovic Institute, and serum IL-8 and IL-17 levels, using ELISA tests. After the operation, resected part of colon will be fixed in paraphine blocks and analyzed at our Department for pathology. There, cancer stage will be determined according to Dukes and TNM classification, as well as cancer infiltration of neutrophils and lymphocytes. Part of the resected specimen will be immunohistochemically analyzed for IL-8 expression in cancer cells and oxidative stress mediators. The collected data will be analyzed, and we hope to determine the influence of colorectal cancer on neutrophil function, prognostic value of neutrophil infiltration of cancer, and the influence of laparoscopic and open colon resection on postoperative recovery of neutrophil function. We will analyze patients who developed postoperative complications, in order to determine possible parameters that would reflect the severity of postoperative complications, or even serve as early markers for postoperative complications, before the onset of clinical symptoms. Institution/University Name of Institution/University Clinical Hospital Dubrava Number of Employees 1600 Number of Researchers 600 Country Croatia Postal Adress Avenija Gojka Suska 6 10000 Zagreb Surgery Research Team Research Team Name Department of Neurosurgery, School of Medicine, Zagreb Individual Researcher No Research Team Leader Name Professor, MD, PhD Josip Paladino Research Team Members Team Member 0 sci.as., MD Dinko Mihaljeviæ [[email protected]] Team Member 1 psychologist, MSc Valerija Hauptfeld [[email protected]] Team Member 2 psychologist, PhD Ljiljana Paèiæ-Turk [[email protected]] Team Member 3 MD, PhD Ante Sekuliæ [[email protected]] Team Member 4 prim., MD Ante Melada [[email protected]] Team Member 5 As., MD, MSc Goran Mrak [[email protected]] Team Member 6 As.prof., MD, PhD Miroslav Vukiæ [[email protected]] Team Member 7 As.prof., MD, PhD Darko Chudy [[email protected]] Team Member 8 Professor, MD, PhD Pavle Mikliæ [[email protected]] Team Member 9 Prof., MD, PhD Josip Paladino [[email protected]] Team Member 10 sci.as., MD Hrvoje Jednaèak [[email protected]] Research Team Projects Project Name Functional neurosurgery Project Leader Professor, MD, PhD Josip Paladino [[email protected]] Project Funding Agency Ministry of Science, Republic of Croatia Project Budget 5000 € Project Start Date 2006-06-01 Project End Date 2011-06-01 Project Partners Croatian Institute for Brain Research, Zagreb Department of Neurology, School of Medicine, Zagreb Department of Radiology,School of Medicine, Zagreb Project Summary Project Website www.kbc-zagreb.hr Contact Person Name Professor, MD, PhD Josip Paladino Email [email protected] Function Chief of Department of Neurosurgery, School of Medicine, Zagreb Phone +38512363530 Fax +38512363531 Website www.kbc-zagreb.hr Research Team Objectives Main Fields Surgery minimally invasive neurosurgery, cerebrovascular neurosurgery, endoscopic neurosurgery, skull base surgery, spinal neurosurgery, radiosurgery (Gamma knife), functional morphology of CNS, surgery of congenital disorders, neurotraumatology Partners/Interests researcher Surgery Institution/University Name of Institution/University University of Zagreb Number of Employees 7817 Surgery Number of Researchers 1108 Country Croatia Postal Adress Trg Maršala Tita 14 10000 Zagreb Surgery Research Team Research Team Name Maxilofacial Surgery Individual Researcher No Research Team Leader Name Mr. MD, PhD, Danijel Žerdoner Research Team Members Team Member 0 Mr. MD, PhD Matjaž Rode [] Contact Person Name Mr. MD, PhD, Danijel Žerdoner Email [email protected] Function Assistant Professor of Maxilofacial Surgery Phone +386 3 423 3000 Fax + 386 3 423 36 66 Website http://www.sb-celje.si/index.php?id=15 Research Team Objectives Main Fields Surgery Maxilofacial Surgery Partners/Interests researcher industrial partner Suitable Surgery 1. IMAGE CYTOMETRIC EVALUATION ON SMEARS OF ORAL MUCOSA: A POSSIBLE APPROACH FOR THE EARLY DETECTION OF ORAL CANCERS AND PRECANCERS Cancer is one of the major threats to public health. In developed countries cancer is the second most common cause of death. It is noteworthy that sharp increases in the incidence rates of oral and pharyngeal cancers have been reported for several EU countries. Despite the progress of modern medicine in the treatment of various cancers, the prognosis of patients with oral cancers is continuously poor. One reason for this is that the diagnosis usually is achieved late. These tumors are generally slow growing and may not arouse suspicion until they ulcerate, become secondarily infected, or invade adjacent structures. Up to 80% oral cancers are not diagnosed on early stage. Therefore, there is an need for new strategies to detect these cancers early. Currently there is intensive research in the development of molecular biomarker assays. Alternatively new techniques of cytoanalysis could be used. One of these approaches is the assessment of structural changes in cell nuclei that derive from the neighborhood of premalignant or malignant lesions. This phenomenon is known as malignancy- associated changes in the DNA organisation. The aim of the study is to investigate the possibility of identifying oral cancers and precancers by nuclear chromatin texture feature analysis of cell nuclei from mucosal scrapings obtained from clinically alternated oral mucosa by high-resolution image cytometry. Institution/University Name of Institution/University General Hospital Celje Number of Employees 1613 Number of Researchers 37 Country Slovenia Postal Adress Oblakova 5 3000 Celje Surgery Research Team Research Team Name Surgery Individual Researcher Yes Research Team Leader Name Mr. MD, PhD Eldar M. Gadžijev Contact Person Name Mr. MD, PhD Eldar M. Gadžijev Email [email protected] Function Professor of Surgery Phone +386 2 321 12 33 Fax + 386 2 331 23 93 Website http://www.sb-mb.si/index.php?id=kirurska-sluzba Research Team Objectives Main Fields Surgery Partners/Interests researcher industrial partner Suitable Surgery 1.ANATOMICAL VARIATIONS OF THE HOLLOW LIVER STRUCTURES AND THEIR SURGICAL IMPORTANCE After separate studies of the hepatic veins, portal vein system, hepatic artery system and biliary system performed on corrosive casts of the cadaver livers congruity and variations in the courses of the elements of portal triad are the matter of research interest in further study. Differences in the course and branches comparing portal vein system and biliary system on the left liver have already been studied, but their presence, frequency and importance inside the right liver have to be searched. When such variations are present they can have important impact on complications and some postoperative morbidity after liver resections. Results of studies should be confirmed using 3D CT pictures in patient cases. Another segment of this study is hepatic venovenous anastomoses which could convert blow flow from the region of one hepatic vein into the region of another after ligating the first one. 2. ABDOMINAL COMPARTMENT SYNDROME AND MEASUREMENTS PROBLEMS Our studies of reproducible liver injury resulted in evaluation of a successful system to achieve it on experimental animal. Precisely labeled cross bow shots using arrows with a ball at the end has given us a possibility to perform a reproducible liver injury. Further problem to be introduced has been evaluation of the pressure of liver packing and specificity of abdominal compartment syndrome. Measurement of the pressure of liver packing is not to be measured like other compartment syndromes. 3. SYMBIOTIC IN PREVENTION OF INFLAMMATORY RESPONSE AFTER MAYOR SURGERY Study of symbiotic support in diminishing inflammatory response after mayor surgery is already going on. Further research is planned to be focused on replacement of antibiotic prophylaxis by symbiotic, leaving antibiotics for treatment when needed. 4. PREVENTION OF BILE DUCT INJURIES DURING LAPAROSCOPIC CHOLECYSTECTOMY Epidemiologic analysis of the bile duct injuries in our country has been recently performed. A study is planned introducing measures with steps and manners during laparoscopic cholecystectomy that should prevent or diminish bile duct injuries. Institution/University Name of Institution/University University of Maribor - Medical faculty Number of Employees 30 Number of Researchers 15 Country Slovenia Postal Adress Slomskov trg 15 2000 Maribor Therapeutics Research Team Research Team Name Centre for Study the Human Motricity-University of Craiova, FEFS Individual Researcher No Research Team Leader Name Prof.dr. RUSU LIGIA Research Team Members Team Member 0 Prof.dr. Stroe Corneliu Andrei [[email protected]] Team Member 1 Prof.dr. Dragomir Marcela [[email protected]] Team Member 2 Prof.dr. Cataneanu Sergiu [[email protected]] Team Member 3 Prof.dr. Dragomir Marian [[email protected]] Team Member 4 Prof.dr. Ortanescu Dorina [[email protected]] Team Member 5 Prof.dr. Avramescu Taina Elena [[email protected]] Team Member 6 Prof.dr. Ortanescu Corneliu [[email protected]] Team Member 7 Prof.dr. Danoiu Mircea [[email protected]] Team Member 8 Prof.dr. Gusti Alice [[email protected]] Team Member 9 Asist. prof.dr. Calinescu Gheorghe [[email protected]] Team Member 10 Prof.dr. Rusu Ligia [[email protected]] Team Member 11 Lecturer Calina Mirela [[email protected]] Team Member 12 Lecturer Vasilescu Mirela [[email protected]] Team Member 13 Lecturer Rosulescu Eugenia [[email protected]] Team Member 14 Lecturer Cernaianu Sorina [[email protected]] Team Member 15 Lecturer Ilinca Ilona [[email protected]] Team Member 16 Asist. Dumitrescu Aurora [[email protected]] Team Member 17 Asist Nanu Costi [[email protected]] Team Member 18 asist. Zavaleanu Mihaela [[email protected]] Team Member 19 asist. Munteanu Germina [[email protected]] Team Member 20 asist. Calinescu Luminita [[email protected]] Team Member 21 asist. Enescu Denisa [[email protected]] Team Member 22 lecturer Barbu Mihai Razvan [[email protected]] Team Member 23 lecturer Ciocanescu Daniel [[email protected]] Research Team Projects Project Name Aquisitions of new skills and practical knowledge for students in kinetotherapy Project Leader Prof.dr. Rinderu Avramescu Taina Elena [[email protected]] Project Funding Agency Project Budget € Project Start Date 2002-10-01 Project End Date 2003-10-01 Project Partners University of Craiova, Romania Clinical Hospital Nr. 1 Craiova, Romania Neurology Hospital Nr. 4 Craiova, Romania Alfa and Omega Tourisme Agency, Craiova , Romania Hogeschool West Vlaanderen Kortrjik, Belgium Cnetre for development of human resources and vocational training, Pyxdia, Greece Totnes European School, Devon, UK Project Summary In this project we promote the role of education and new aquisitions skills of students at kinetotherapy for increase their theoretical and practical prepare regards the last european standards. Traget group-13 students and kinetotherapy that go to educational institutions in Europe for 3 months. Therapeutics Project Website http//cis01.central.ucv.ro/en/educatie_fizica Project Name Training Centre for Health Care, Prophylactic and Rehabilitation Services Project Leader Prof.dr. Rinderu Avramescu Taina Elena [[email protected]] Project Funding Agency Project Budget € Project Start Date 2005-10-01 Project End Date 2007-03-01 Project Partners University of Craiova,Romania Prefecture of Dolj, Romania University Foundation of Kinetotherapy, Oradea, Romania University of Oradea, Romania Hogeschool West Vaanderlenden Kortrjik Belgium Entente,UK SCUE/Studio di consulenza per l"Unione Europea , Italy Technical University of Crete, Greece Project Summary Deveoplment the reserach centre for rehabilitation the disabilities perssons, using the prohylactic services and alsostudents participation to development the research activity regards the role of physical activity in rehabilitation. Change from our lecturer and specialists with other specialists form European country. Project Website http//cis01.central.ucv.ro/en/educatie_fizica Project Name Alghoritm for implementation the physical activity in rehabilitation of neuromuscular disorders Project Leader Prof.dr. Rusu Ligia [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-03-01 Project End Date 2007-03-01 Project Partners University of Craiova, Romania Nuerologyc Hospital Craiova, Romania Project Summary It is a national programme for research, that are organise by CNCSIS and Ministery of Education in Romania. The project research the modalities for introduce the physical activity in rehabilitation programme for patients with neuromuscular disorders, and create some assesment scale for prevent thedecrease the health status of these patients and for prevent the muscle weakness and fatigue. Project Website http//cis01.central.ucv.ro/en/educatie_fizica Contact Person Name Prof.dr. RUSU LIGIA Email [email protected] Function Director of Research Centre Phone 0040251563755 Fax 0040251422090 Website www.ucv.central.ro Research Team Objectives Main Fields Therapeutics Physiology Social medicine Main fields of our centre is to study the numan body motricity and performance, the role of physical effort in increase and improvement the health status. We have also study regards the implication of physical activity in rehabilitation of patients with multiple sclerosis. We made study regards physiologycal and morphologycal aspects that are the results of physical activity in neuromuscular disorders and osteoporosis and also fpr prevent the ageing process. We are preocupate for development the research related kinetic analyse of body movement and how we can increase the apport of these results in rehabilitation and prevention programme. Therapeutics Partners/Interests researcher industrial partner Biophysics Physiology Therapeutics Experience in research of human body, physiology, rehabilitation, morphophysiology in neuromusuclar disorders, osteoporosis and ageing. We want to devlopment the research regards movement analyse of human body and the implication of physical activity in rehabilitation of perssons with chronic disease for increase the health statuts and so to reduce the social costs. We want to development the study regards ageing and how the physical activity can improve the life at elderly people. Development the reserch in multiple sclerosis and the role of physical activity in change the morphophysiologyc aspects in multiple sclerosis. Institution/University Name of Institution/University University of Craiova, Physical Education and Kinetotherapy Number of Employees 1000 Number of Researchers 150 Country Romania Postal Adress A.I.Cuza 13 1100 Craiova Therapeutics Research Team Research Team Name Department of Oncology and Nuclear Medicine, Sisters of Charity University Hospital, Zagreb, Croatia Individual Researcher No Research Team Leader Name Professor Josip Lukac Research Team Projects Project Name RT-PCR determination of circulating tumor cells in patients with solid tumors Project Leader Prof Josip Lukac [[email protected]] Project Funding Agency Project Budget € Project Start Date 2006-01-01 Project End Date 2011-12-31 Project Partners Project Summary Metastases are the major cause of cancer-related deaths in patients with solid epithelial tumors. Hematogenous spreading of tumor cells is considered as a crucial step in tumor dissemination. Therefore, the detection of disseminated tumor cells in peripheral blood might be of clinical significance with respect to individual patient prognosis and monitoring of therapy. Reverse transcriptase-polamerase chain reaction (RT-PCR) assay allows determination of molecular tumor markers expressed in disseminated tumor cells, thus providing a powerfull tool for detection of disseminated tumor cells with high sensititity and specificity. Colorectal cancer (CRC) is the third cause of death of cancer patients in EU. Although systematic colonoscopic examinations gratly contributed to early diagnosis of CRC and allowed earlier surgical interventions, substantial proportion of patients die from recurrences and/or distant metastases. More reliable prognostic factors would allow more accurate identification of these increased-risk subgroups. Based on its restricted expression pattern, cytokeratin 20 (ck20) has been mainly used as a tumor marker to detect tumor cells in the peripheral blood of patients with CRC but the results regarding its specificity and clinical usefulness are still conflicting. Some studies showed that ck20 is a reliable marker, not detectable in the blood of noncancer patients, while others detected it in a proporton of patients with non-tumor disease so that its sensitivity/specificitiy and the usefulness as a prognostic marker still needs to be evaluated. Also the evidence about the usefulness of detection of tumor cells in mesenteric blood taken intraoperatively, as a more reliable predictor of liver metastases is scarce and should also be evaluated as should be the detection of tumor cells in peripheral blood taken intraoperatively, as a predictor of tumor disssemination mediated by the surgical procedure itself. Although not among tumors with the highest incidence, malignant melanoma represents a huge healthcare problem because its incidence is significantly increasing in the last few decades and because there is still no available treatment option that would significantly prolong the survival of patients with advancedstage disease. Therefore, it is important to find biological markers which would be predictive particularly for spreading of metastases and could help to improve the management of patients. The detection of circulating melanoma cells by RT-PCR is being investigated as a potential prognostic marker and marker for monitoring response to therapy. The most widely used melanoma-specific marker in RT-PCR detection of circulating melanoma cells is the expression of tyrosinase gene (Tyr). The major limitation in clinical use of tyrosinase as a marker is a relatively high number of melanoma patients with clinically confirmed distant metastases being tyrosinase negative. It has been shown that determination of Melan-A/MART-1 in addition to tyrosinase enables the RT-PCR detection of circulating melanoma cells in a larger percentage of melanoma patients. We were first to show that analysis of microphthalmia-associated transcription factor (MiTF) as an additional marker to tyrosinase enables the detection of circulating melanoma cells in a larger percentage of melanoma patients. Therefore, the usefulness of multiple marker detection in increasing of sensitivity needs to be further elucidated. Although much progress has been made in the treatment of differentiated thyroid cancer, disease recurrence and metastases may still occur in 20 – 40 % of patients. Since most of the recurrences can be managed successfully by surgical and radioiodine treatment it is important to monitor patients after thyroidectomy to detect a recurrence as early as possible. Measurement of serum thyroglobulin (Tg) protein by immunoassay is commonly used highly specific test for detecting recurrent or residual thyroid cancer. A major limitation of this test is a presence of anti-Tg antibodies in 10-20 % of patients, which interferes with serum Tg measurement. There has therefore been an interest in developing new sensitive assays for thyroid cancer detection that are not influenced by presence of anti-Tg antibodies. One such approach is detection of circulating thyroid Therapeutics cancer cells by RT-PCR. The most widely studied thyroid-specific marker in RT-PCR detection of circulating thyroid cancer cells is the expression of Tg gene. The prognostic value of circulating thyroid cancer cells detection by RT-PCR hasn’t been studied so far. We would like to study the prognostic value of determination of circulating tumor cells by RT-PCR: (i) in peripheral blood prior to surgical resection of primary tumor and intraoperatively, in mesenteric blood intraoperatively, in peripheral blood at each follow-up visit for three post-operative years, and/or prior to and following rasdiotherapy/chemotherapy in colorectal cancer patients (marker: cytokeratin 20); (ii) in peripheral blood of melanoma patients prior to surgical resection of primary tumor and at each follow-up visit for three post-operative years and/or prior to and following chemotherapy in those requireing further treatment (markers: tyrosinase and microphthalmia transcription factor); and (iii) in peripheral blood of patients with differentiated thyroid cancer at each follow-up visit throughout the first three years following tumor resection (thyroglobulin as a marker). Project Website Contact Person Name Professor Josip Lukac Email [email protected] Function Head, Division of Laboratory Diagnostics Phone +3851 3787 228 Fax +3851 3768 303 Website www.kbsm.hr Research Team Objectives Main Fields Therapeutics Therapeutics Immunology and Immunohaematology Oncology; tumor markers; circulating tumor cells by RT-PCR; colorectal cancer; melanoma; thyroid cancer Partners/Interests researcher Therapeutics Genetics Immunology and Immunohaematology Facilities and knowledge in performing PCR and RT-PCR Applied/clinical research of the usefulness of determination of circulating tumor cells detected by RTPCR as a prognostic factor in patients with solid tumors (particularly colorectal cancer, melanoma, thyroid cancer and breast cancer). Institution/University Name of Institution/University Sisters of Mercy University Hospital Number of Employees 2290 Number of Researchers 116 Country Croatia Postal Adress Vinogradska 29 10000 Zagreb Therapeutics Research Team Research Team Name Ortopaedics Individual Researcher Yes Research Team Leader Name Mr. MD, PhD Samo Fokter Contact Person Name Mr. MD, PhD Samo Fokter Email [email protected] Function researcher Phone +386 3 423 30 00 Fax + 386 3 423 36 66 Website www.sb-celje.si Research Team Objectives Main Fields Therapeutics Ortopaedics Partners/Interests researcher industrial partner Suitable Therapeutics Use of bisphosphonates to improve the durability of total hip replacement Total joint replacements are effective surgical procedures for treating patients with end-stage arthritis. However, this procedure is associated with an incidence of failure that increases at the rate of approximately 1% per year postoperatively. Failure is often due to aseptic loosening with bone loss surrounding the implant. Particularly around total hip arthroplasties (THA), insertion of a stiff metal implant alters the loading pattern of the surrounding bone. Body weight is transferred along the implant to the femoral diaphisis, thereby bypassing the proximal femur (stress shielding). This removal of load results in early periprosthetic bone loss (i.e. 3 to 6 months following THA), which may exceed 30% of the bone mass as determined by dual-energy X-ray absorptiometry (DXA). If allowed to progress, implant stability may be compromised resulting in complications such as implant destabilization and periprosthetic bone fracture. Revision surgeries have a higher rate of local and systemic complications, requiring longer hospital stays; they have less favorable outcomes, and are more expensive than the initial surgery. Bisphosphonates effectively inhibit bone resorption and are the pharmaceutical agents of choice in managing postmenopausal osteoporosis, hypercalcaemia, and Paget’s disease. Bisphosphonates bind avidly to hydroxyapatite crystals and thus have a strong affinity for bone mineral. During bone remodeling process, osteoclasts take up the bisphosphonate, which inhibits the mevalonate pathway. Osteoclasts lose the ruffled border and are inactivated as a result of apoptosis. Several studies have shown that bisphosphonates, administered systemically, may be effective in preventing the bone loss associated with stress shielding. Since bisphosphonates have some side effects like fever, throat or stomach ulcers as well as a low bioavailability, local delivery with the implant coated with a bisphosphonate would be highly appreciated. The bone in contact with the implant will be the only part of the skeleton being exposed to the drug. This is important as patients undergoing THA do not necessarily present osteoporosis. We aim at determining whether a bisphosphonate locally released from an implant could decrease the periprosthetic bone loss after THA. The study design will be prospective, randomized, and blind. Periprosthetic bone mineral density (BMD) will be measured with DXA at total periprosthetic area as well as at seven Gruen zones or regions of interest. DXA scans will be performed at one week (baseline), six weeks, three months, six months, and 12 months postoperatively. Mean values of the demographics, BMD, and baseline-normalized BMD values will be compared between the bisphosphonate and placebo groups at each time point. For all temporal measurements including BMD and normalized BMD, mean values will be compared across each time point within a given group. In that manner, it would be possible to show if bisphosphonate covering of the endoprosthesis could potentially increase the longevity of the THA and thus decrease the necessity for revisions, reduce patient suffering, and lessen the costs for the society. Institution/University Name of Institution/University General Hospital Celje Number of Employees 1613 Number of Researchers 37 Therapeutics Country Slovenia Postal Adress Oblakova 5 3000 Celje Therapeutics Research Team Research Team Name Individual Researcher Yes Research Team Leader Name Prof. dr. Meliha Lekić PhD Contact Person Name Prof. dr. Meliha Lekić PhD Email [email protected] Function Head of the Department of Haematology Phone +33 663 742 / 743 Fax +33 203 670 Website www.mf.unsa.ba Research Team Objectives Main Fields Therapeutics Partners/Interests AN EVALUATION OF OXIDOREDUCTION PROCESSES OF FITTED ORTHOPEDIC IMPLANTS MADE OF ALLOYED STAINLESS STEEL BY MONITORING THE LEVEL OF ALLOY ELEMENTS IN BODY FLUIDS The choice of materials for orthopedic implants depends on their mechanical and chemical biocompatibility. Biological environment (body fluids) with high concentration of chloride ions and various complexifying agents stimulate the decomposition of the material, releasing metallic ions in the surrounding tissues. The ions are transported through the body: they link with proteins, enter the cells of surrounding tissues and stay at the implant’s place, or they are reduced and become inert. These processes are exceedingly interesting from the medical point of view, since the research of the impact of various oxidizing metal conditions helps to explain some illnesses occurring in patients with fitted orthopedic implants. Stainless steel is the most susceptible to oxidoreduction processes among orthopedic materials. If the concentrations of alloy elements exceed normal values, all three main elements – iron, chrome and nickel – are potential carcinogens for humans. It is well known that nickel can cause toxic and allergic reactions, resulting in cell destruction. Chrome, which is the highest percentage alloy element in these alloys (17 to 19%), shows genotoxic characteristics in the form of Cr6+ ion. The stainless steel implant’s degradation manifests in the higher concentration of iron, chrome and nickel in urine, lungs, liver, kidneys and spleen. These values can even exceed normal ones ten times. Hypothesis Monitoring the physicochemical metal implants corrosion parameters in vitro correlated with determination of implant’s alloy elements concentration in vivo, it is possible to predict how long particular metal implants can stay in the body before causing significant disturbances triggered by degradation processes of implants themselves. Probably the results will depend from quality and quantity of implant materials in different countries of South-East Europe. Research aims • Monitor oxidoreductive processes of the fitted orthopedic implants by monitoring the level of alloy elements of the implant in body fluids. • Define types of oxidoreductive processes on implants with various purposes. • Define oxidoreductive processes parameters on stainless steel implants. • Determine corrosion speed on stainless steel implants in vitro in simulated in vivo conditions. Participants Serum and 24 hours urine of patients will be analyzed according to a predetermined plan in preset time intervals, from the implant’s fitting to its removal. The control group would consist of the same participants whose blood and one-time urine would be taken immediately before fitting. Methods applied Atomic absorption spectrophotometry with graphite furnace cuvette will be used for determination of alloy metals concentration in body fluids. Chemical stability of implant materials will be tested in vitro, in simulated physiological conditions (electrolyte solution, pH, temperature, pressure) by application of electrochemical methods using potentiostatic and galvanostatic techniques. Results expected Obtained results of oxidoreductive processes in implantation materials research could depend from Therapeutics quality and quantity of that materials and can be important for orthopedists and casualty surgeons. Based on them it will be possible to determine how long a certain metal implant can stay in the body to achieve the full osteosynthetic effect without causing any important risk of possible intoxication by ions of alloy elements. Institution/University Name of Institution/University University of Sarajevo, Faculty of Medicine Sarajevo Number of Employees Number of Researchers Country Bosnia and Herzegovina Postal Adress Čekaluša 90 71000 Sarajevo Therapeutics Research Team Research Team Name Individual Researcher No Research Team Leader Name Prof. Željiko Knez Research Team Members Team Member 0 Zoran Novak [[email protected]] Team Member 1 M. Škerget Contact Person Name Prof. Željiko Knez Email [email protected] Function Phone +386 2 2294461 Fax +386 2 2516750 Website http://atom.uni-mb.si/labs/lab_sep/engindex.htm Research Team Objectives Main Fields Therapeutics Pharmacology Partners/Interests INOVATIVE PROCESSES FOR INOVATIVE DRUGS Many drugs possess poor water solubility and their bioavailabilities are limited by their dissolution rates. Several approaches are known to increase the dissolution rate and hence the bioavailability of such drugs including micronization, formation of solid dispersions, solvates, adsorbates or complexes. Technologies using supercritical fluids (SCFs) can also be used in this sense. Beside their extractive, chromatographic and applications in biochemical reactions, SCFs offer interesting applications in materials processing. In recent years, processing of pharmaceuticals with SCFs, especially with supercritical carbon dioxide, has received increased attention. Supercritical micronization techniques are: rapid expansion of a supercritical solution (RESS), gas anti-solvent recrystallisation (GASR), high pressure crystallization (HPC) and particles from gas saturated solutions (PGSS). The PGSS method shows some advantages over RESS, GASR and HPC processes. Compared to RESS the consumption of CO2 is an important parameter being lower by an order of magnitude 103 for PGSS than for RESS. Since in RESS the substance has to be dissolved in the supercritical gas, sufficient solubility in SC CO2 is the criterion which eliminates many pharmaceutical compounds from the RESS process. In PGSS on the contrary, the compressible gas is dissolved in the molten compound and the gas saturated liquid phase is further processed. When compared to GASR advantageously no organic solvent is needed in the PGSS process. With the PGSS process micronized drugs and drug composites can be prepared in different way, which has some advantages over classical methods for micronization of pure drugs and for drug/carrier solid dispersion preparation, namely fusion methods and solvent processes. In the PGSS process there is a melt of the drug (and a carrier), saturated with supercritical CO2. Upon expansion the gas evaporates and therefore this solution is rapidly cooled down and the drug (or drug/carrier) precipitates in form of microparticles, thereby avoiding the comminution step. Since the cooling is rapid due to the expansion of CO2 present fine particles with a narrow particle size distribution can be formed. With the PGSS process, micronized drug or micronized drug/carrier can be obtained in one step with no organic solvent. The condition for successful micronization with the PGSS process is sufficient solubility of supercritical CO2 in the melt to achieve the expandable gas saturated solution. Institution/University Name of Institution/University Faculty of Chemistry and Chemical Engineering, University of Maribor Number of Employees Number of Researchers Country Slovenia Postal Adress Smetanova ul. 17 2000 Maribor Therapeutics Research Team Research Team Name Evidence-based medicine Individual Researcher No Research Team Leader Name Univ. Doz. Dr. Andrea Siebenhofer-Kroitzsch Research Team Members Team Member 0 OA Dr. Karl Horvath Team Member 1 Dr. Klaus Jeitler Contact Person Name Univ. Doz. Dr. Andrea Siebenhofer-Kroitzsch Email [email protected] Function head of the EBM Review Center Phone Fax Website http://www.meduni-graz.at Research Team Objectives Main Fields Therapeutics Evidence-based medicine Partners/Interests The central function of Review Centers ist the implementations of an systematic overview and metaanalyses of precisely defined medical items and problems. These subsequently represent the basis for decisions regarding supply in health care, health technology assessments, disease management programs or guidelines and serve as assistance för diagnostic and therapeutic decisions of attending physicians. Additional functions include the procurement of EBM-competences for attending physicians in form of training courses as well as the further development of methods for the evaluation of surveys and training of medical students. Institution/University Name of Institution/University EBM-Review Center, Medical University Graz Number of Employees Number of Researchers Country Austria Postal Adress Auenbruggerplatz 8036 Graz Toxicology Research Team Research Team Name Laboratory of environmental and clinical analytical toxicology and environmental health problems Individual Researcher No Research Team Leader Name PhD in analytical chemistry Alina Catrinel Ion Research Team Members Team Member 0 PhD student Anton Ficai [[email protected]] Team Member 1 PhD student Cornelia Dragnea [[email protected]] Team Member 2 professor Ana Banica [[email protected]] Team Member 3 professor Ion Ion [[email protected]] Team Member 4 professor Alina Ion [[email protected], [email protected]] Contact Person Name PhD in analytical chemistry Alina Catrinel Ion Email [email protected] Function professor Phone 0723295334 Fax +440212319492 Website www.acad.ro Research Team Objectives Main Fields Toxicology Social medicine Clinical chemistry environmental and environmental health problems; metal ion speciation and its applications in human health; modern trends of metal ions research, speciation, quality, assurance and risk assesement environmental pathology and exposure to metal ions; nutrition, metal ions and ageing Partners/Interests researcher industrial partner Toxicology Information Technology, Statistics, Documentation Clinical chemistry researchers and industrial partners in the field of public health Cu, Cd, Zn, Pb, Al speciation in environmental and clinical samples; study of their multiple effects over human health Institution/University Name of Institution/University University Politehnica of Bucharest Number of Employees 5000 Number of Researchers 1600 Country Romania Postal Adress Polizu street 1 78123 Bucharest Toxicology Research Team Research Team Name Medical faculty Foca University East sarajevo, Bosnia and Hercegovina Individual Researcher No Research Team Leader Name associate professor Veljko Maric Research Team Members Team Member 0 associate professor, Veljko Maric dean, surgeon [] Team Member 1 assistant professor Stevan Trbojevic vicedean, gastroenterologist [] Team Member 2 professor Slobodan Milovanovic pharmacologist [] Team Member 3 assistant professor Sinisa Ristic physiologist, [] Team Member 4 assistan professor Milan Kulic genetics [] Research Team Projects Project Name Balcanic endemic nephroparhy in BiH Project Leader dean, associate professor Veljko Maric [[email protected]] Project Funding Agency Project Budget € Project Start Date 2007-01-01 Project End Date 2010-01-01 Project Partners Project Summary We should investigate epidemiological, clinical, biochemistry, genetical characteristic of patient with BEN and their family member. Project Website Contact Person Name associate professor veljko maric Email [email protected] Function dean Phone 0038758 210 420 Fax 0038758 210 007 Website http://www.mf-foca.com Research Team Objectives Main Fields Toxicology Internal Medicine Epidemiology Balcanic endemic nephropathy in BiH (Biljeljina region) Partners/Interests Biology Institution/University Name of Institution/University medical faculty Number of Employees 70 Number of Researchers 20 Country Bosnia and Herzegovina Postal Adress Solunskih dobrovoljaca 1 73300 Foca Toxicology Research Team Research Team Name Mineral Metabolism Unit Individual Researcher No Research Team Leader Name M.D., Ph.D. Martina Piasek Research Team Members Team Member 0 M.D., Ph.D., F.C.A. Krista Kostial-Šimonović [[email protected]] Team Member 1 Ph.D. Maja Blanuša [[email protected]] Team Member 2 B.Sc. Tatjana Orct [[email protected]] Team Member 3 B.Sc. Maja Lazarus [[email protected]] Team Member 4 M.D., Ph.D. Veda Marija Varnai [[email protected]] Team Member 5 M.Sc. Dijana Jureša [[email protected]] Team Member 6 Ph.D. Jasna Jurasović [[email protected]] Team Member 7 M.D., Ph.D. Martina Piasek [[email protected]] Research Team Projects Project Name Exposure, intake and effects of toxic and essential elements Project Leader Dr. Martina Piasek [[email protected]] Project Funding Agency Croatian Ministry Sci. Edu. Sports Project Budget 170.000 € Project Start Date 2002-07-24 Project End Date 2006-12-31 Project Partners Investigators in Croatia, Institute for Medical Reasaech and Occupational Health: Veda Marija Varnai Selma Cvijetiæ Avdagiæ Dijana Jureša Tatjana Orct Maja Lazarus Maja Blanuša Krista Kostial Collaborators from USA: Jasminka Z. Ilich Velimir Matkoviæ John W. Laskey Project Summary Toxicokinetics of metals (cadmium, lead, mercury) and interactions of toxic and essential elements (calcium, iron, zinc, copper, selenium); Reproductive and perinatal health effects of metals (particularly cadmium) and assessment of bone health especially in young in man and animals; Influence of age, nutrition, and chelation therapy on metal toxicokinetics and health effects in experimental rats; Testing of novel chelating agents and dietary measures for reducing toxic metal body burden in experimental rats. Biomonitoring and monitoring of metals and metalloids by analysis of various elements in biological materials (human and animal), food, water, and soil by atomic absorption spectrometry, flame and electrothermal AAS (As, Ca, Cd, Cu, Fe, Hg, Mn, P, Pb, Se, Zn). Project Website //bib.irb.hr/pregledi?chset=ASCII〈=EN Project Name Biomedical research on reproduction and development (research on placenta and metal exposure) Project Leader Professor Davor Ježek [[email protected]] Project Funding Agency Project Budget € Project Start Date 2003-11-20 Project End Date 2006-12-31 Project Partners Part of a national collaborative research project at Zagreb University Medical School Project Website Contact Person Name M.D., Ph.D. Martina Piasek Email [email protected] Function Scientific Adviser Toxicology Phone ++385 1 4673 188 Fax ++385 1 4673 303 Website http://www.imi.hr/index.php?lang=en Research Team Objectives Main Fields Toxicology Pharmacology Public health services Evaluation of toxicokinetics and health effects of toxic and essential elements: Health effects of toxic metals (cadmium, lead, mercury, aluminium) and interactions of toxic and essential elements (calcium, iron, zinc, copper, selenium), particularly reproductive and perinatal effects and bone health; Influence of age, sex, nutrition, and chelation therapy on metal toxicokinetics and health effects in experimental rats; Testing of novel chelating agents and dietary measures for reducing toxic metal body burden in experimental rats. Monitoring and assessing environmental exposures to metals and metalloids by analysis of various elements in biological materials (human and animal), food, water, and soil by atomic absorption spectrometry (flame and electrothermal AAS): Ag, Al, As, Ca, Cd, Cu, Fe, Hg, Mn, P, Pb, Pt, Se, Zn. Partners/Interests researcher Toxicology Clinical chemistry Public health services Experiance in steroid hormone analysis to assay placental tissue steroid hormones. Assesment of exposure and effects of metals as endccrine disupting chemicals by placental metal concentrations and placental steroidogenesis in human and experimental rat. Institution/University Name of Institution/University Institute for Medical Research and Occupational Health, Zagreb Number of Employees 147 Number of Researchers 84 Country Croatia Postal Adress Ksaverska cesta 2 10001 Zagreb
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