Cel VALIDATION OF NEW IN VITRO TESTS FOR THE PREVISION OF NERVOUS SYSTEM TERATOGENESIS BY DRUGS. The teratogenic potential of pharmaceutical agents was evaluated in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay employing primary cultures of cerebral cortex neurons at different stages of their development. Anticonvulsant agents with an ability to induce neural tube defects in vivo, valproate and the benzodiazepines (diazepam and clonazepam), were shown to have an antiproliferative action in neuroblastoma and glioma cell lines at 2-3 times their therapeutic serum concentrations and this was not due to cytotoxic action. Agents with a cytoxic action (phenytoin and some barbiturates) could be associated with their known in vivo impairment of neurodevelopment. Nonteratogenic analogues of valproate had no antiproliferative effect in clonal cell lines and the cytotoxic effect of certain barbiturates on primary cortical neurons had a specific structure activity requirement. In vivo systems evaluating induction of early differentiation markers and change in adhesiveness had poor discriminatory potential. The convulsive agent lindane was shown to inhibit picrotoxin binding and to facilitate transmitter release in vitro.ESTABLISH THE BASES FOR IN VITRO TESTING ON CELL CULTURES OF THE TERATOGENESIS INDUCED BY ANTICONVULSIVANTS, INCLUDING NEURAL TUBE DEFECTS, CRANIOFACIAL ABNORMALITIES AND MENTAL RETARDATION. THIS WILL INVOLVE DESIGNING CELL TOXICITY, ANTI-MITOTIC, PRO-DIFFERENCIATIVE AND ADHESION ASSAYS. Dziedzina nauki natural sciencesbiological sciencesneurobiology Program(-y) FP1-BAP - Multiannual research action programme (EEC) in the field of biotechnology (BAP), 1985-1989 Temat(-y) Data not available Zaproszenie do składania wniosków Data not available System finansowania CSC - Cost-sharing contracts Koordynator UNIVERSITY OF COPENHAGEN Wkład UE Brak danych Adres NOERREGARDE 10 POSTBOKS 2117 KOEBENHAVN 1017 Dania Zobacz na mapie Koszt całkowity Brak danych Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITY COLLEGE Irlandia Wkład UE Brak danych Adres BLACKROCK CO. DUBLIN Zobacz na mapie Koszt całkowity Brak danych