[Modified indicators of stillbirth and infant and neonatal mortality].
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Biomedical subjects
Publications and source records attributed to V Srb.
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Platinum-based preparations, the commercially available Platidiam (Lachema, Brno; cis-diaminodichloroplatinum) and the second generation experimental version--ethylmalonate platinum complex--EM-Pt (Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, Prague) were left to act 3, 6 and 24 h on human peripheral blood lymphocytes, cultured in vitro for a short period of time. The utilized concentrations affected cell mitosis, provoking chromosome aberrations. A relationship was found between the effect of the concentration employed and the duration of action of the agent. cis-DDP proved to be a more powerful clastogenic agent than EM-Pt. Under in vitro conditions, neither of the two cytostatics required metabolic activation to trigger its action.
Analyses of mitotic activities and chromosome aberrations in lymphocytes of human peripheral blood have been utilized to evaluate 24-hour cytotoxic and genetic effect of various concentrations (0, 12, 60, 120, 240, 360 mumol l-1) of ethylmalonate platinum (EM-Pt) in vitro. EM-Pt was found to exert a mutagenic action, to have the character of a clastogenic agent and to affect primarily the G1-phase of the cellular cycle. Its activity may be affected by the concentration of the agent: a direct dependence was observed as regards occurrence of chromosome aberrations and an indirect one with regard to values of mitotic activity and cytotoxicity.
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The mutagenic activity of the cytostatic drug Platidiam (cis-diamminedichloroplatinum II complex, cis-DDP) produced in Czechoslovakia was tested. In the used Ames test, as an indicator system, Salmonella typhimurium his- strains were employed. The tests for mutagenicity were performed in vitro using assays both without metabolic activation and therewith, as well as with metabolic activation under in vivo conditions. The analyses revealed a mutagenic effect of the cis-DDP complex in Platidiam in all of the followed tests. These effects were direct, no metabolic activation was observed. Furthermore, the mutagenic activity of the drug was influenced by the duration of interaction between Platidiam and the mammalian organism, which was apparently due to the pharmacokinetic properties of the active substance.
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The cytogenetic activities of 3 growth-promoting agents carbadox, olaquindox and cyadox were examined by the micronucleus test. These chemicals were administered i.p. to male Wistar rats 30 and 6 h before they were killed. Single-dose levels were 5, 10, 15, 30, 60, 90, 120 and 240 mg/kg for carbadox; 30, 60, 90, 120 and 240 mg/kg for olaquindox; and for cyadox 30, 60, 120 and 240 mg/kg. Over the entire dose range tested, carbadox induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes in the rat bone marrow, whereas similar activity of olaquindox started at a dose of 2 X 60 mg/kg. The effect of cyadox was very low even at the highest dosage tested. Further testing of the genotoxicity of this class of chemicals is required. The genetic activity of the solvent used (dimethyl sulfoxide) is briefly discussed.
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The cytogenetic effects of cytostatic drug Platidiam Lachema (cis-diamminedichloroplatinum (II) complex, cis-DDP) have been studied employing short-term in vitro cultivation of human peripheral lymphocytes. Three hours following the administration of cis-DDP at a concentration of 12.5 microM (that is a concentration approximately 10 times lower than that applied clinically at a single dose), chromosome aberrations (predominantly breaks, in 73% those of the chromatid type) were seen at an increased rate. They reached their maximum after 24 h of treatment. A time dependence has been revealed: with decreasing mitotic activity and prolonged time of cis-DDP treatment (3, 6, 18, 24, 48, 72 h, respectively) the number of cells with aberrant chromosomes increased, this elevation being statistically significant from 18 h on.
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