[Analogs of nucleic acid bases as antimetabolites. 1].
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Biomedical subjects
Publications and source records attributed to O Wassermann.
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1. The influence of the anorectic drugs fenfluramine, mazindol, mefenorex, phentermine and R 800, an experimental compound, on pulmonary vascular resistance has been studied in the isolated, perfused rat lung. 2. R 800 caused a strong vasoconstriction, which was not antagonized by methysergide of phentolamine; the other drugs listed did not alter vascular resistance. 3. Mazindol and phentermine significantly prolonged the vasoconstrictive effect of serotonin due to inhibition of its metabolic breakdown. 4. Although fenfluramine inhibited serotonin metabolism it also prevented the vasoconstrictive effect of serotonin, due to its ability to act as a serotonin antagonist. 5. Mefenorex did not affect pulmonary vascular resistance, either directly or indirectly via a serotoninergic mechanism.
The kinetics of tritiated metoprolol and its metabolites have been determined after intravenous and oral administration in dialysis patients. The kinetic behaviour of metoprolol in these patients does not differ from that in healthy volunteers, since its elimination depends on hepatic metabolism. The pharmacologically less active metabolite alpha-hydroxymetoprolol is formed to an individually varying degree and its half-life is prolonged. The concentration of the total radioactivity, which represents the sum of all metabolites, does not decline in the dialysis interval. During haemodialysis, however, its concentration decreases with a half-life of 5h. It might be assumed, that dialysis of these polar compounds is rather nonspecific and that it depends essentially on the dialysis technique.
The widespread use of the persistent and lipophilic polychlorinated biphenyls (PCB) e.g. in electrical engineering, hydraulics and chemistry of the polymers, caused their ubiquitous distribution and accumulation in food chains. Chronic toxicity in humans is known from several incidents of PCB contaminated food. Dose-response experiences, however, remain uncertain due to the technical grade of PCB as a complex mixture of about 150 congeners and many impurities, like polychlorinated dibenzodurans. Some information on the toxicity of a few PCB congeners is available from animal experiments. Large differences in enzyme-inductive efficacy between the PCB congeners rendered the use of toxicity equivalent factors (related to 2,3,7,8-TCDD, "Seveso-Dioxin") necessary. For risk assessment, the use of "sum of PCB", calculated from questionable determinations of 6 minor toxic congeners, is insufficient. Serious problems arise from evaporation of PCB e.g. in technical rooms of telephone companies (in Germany: Telekom) and generally, from sealing materials in buildings. The German Federal Health Administration, BGA, recommends 300 ng total PCB/m3 indoor air as "precautionary value". Since neither the extreme differences in toxicity of the congeners nor bioaccumulation are taken into account, this recommendation of BGA can not be justified any longer.