Objective
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 BASIS FOR IN VITRO TESTING ON CELL CULTURES OF THE TERATOGENESIS INDUCED BY ANTICONVULSANTS, INCLUDING NEURAL TUBE DEFECTS, CRANIOFACIAL ABNORMALITIES AND MENTAL RETARDATION. THIS WILL INVOLVE DESIGNING CELL TOXICITY, ANTI-MITOTIC, PRO-DIFFERENTIATIVE AND ADHESION ASSAYS.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
BLACKROCK
Ireland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.