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Biomedical subjects

H Peter

Publications and source records attributed to H Peter.

94 records · Page 6Linked to original sources

Stereoselectivity of in vitro isoprene metabolism.

The stereoselectivity of the in vitro conversion of isoprene by liver enzymes of rats and mice was determined. Isoprene was epoxidized by cytochrome P450 of rats and mice to 2-isopropenyloxirane and 2-methyl-2-vinyloxirane with slight but different product enantioselectivity. Only with mouse liver microsomes was a distinct regioselectivity observed. Both monooxiranes were further epoxidized to 2-methyl-2,2'-bioxirane with substrate enantioselectivity, product diastereoselectivity, and with product enantioselectivity. The epoxide hydrolase-catalyzed hydrolysis with rat and mouse liver microsomes occurs with substrate enantioselectivity. A better kinetic resolution was found for 2-isopropenyloxirane than for 2-methyl-2-vinyloxirane. While 2(R)-isopropenyloxirane was conjugated preferentially with glutathione, catalyzed by glutathione S-transferase, no enantiomer differentiation takes place in the case of 2-methyl-2-vinyloxirane.

Animals↗

Increasing the safety of volumetric ultrafiltration control.

Deviations in ultrafiltration volume can cause various problems for patients undergoing a haemodialysis treatment. With the introduction of high flux dialysers, closed systems with volumetric fluid balancing became the systems of choice, because control of transmembrane pressure used previously is too inaccurate and unsafe to be used with such filters. In this article, a reliable and cost effective test method is described to increase the safety of a closed system. The test is carried out by simply analysing the dialysate pressure while the dialyser is isolated from the system for typically 7.2 seconds. No additional sensors and components other then a valve combination used to isolate the dialyser are required.

Bias↗

Experimental pharmacokinetics and toxicology of acrylonitrile.

Pharmacokinetic experiments in rats and Rhesus monkeys show that inhaled acrylonitrile is nearly completely retained and metabolized. Metabolism, according to the literature, proceeds via direct reaction of acrylonitrile with biological sulfhydryl compounds and, to a much lesser extent, via glycidonitrile as a DNA-reactive oxidative metabolite. Clinical symptoms of acute acrylonitrile intoxication are in favour of an increased parasympathetic activity. This is confirmed by increased release of acetylcholine, in presence of acrylonitrile, from isolated chicken hearts of which the N. vagus is electrically stimulated. This explains an antidotal effect of atropine. The effectiveness of N-acetyl-cysteine as an acrylonitrile antidote may be explained by decreased alkylation and inactivation of acetylcholine-esterase.

Acrylonitrile↗

Clinical toxicology of acrylonitrile.

Acrylonitrile monomer is used in the production of artificial fibres and resins. It has been used as a fumigant. Acrylonitrile has acute toxic effects for men and animals on over-exposure by inhalation of the vapor, dermal absorption of the liquid and oral intake. Symptoms in men are non-specific and predominantly related to the central nervous system, the respiratory tract, the skin and to the gastrointestinal tract. Severe acrylonitrile intoxication is followed by loss of consciousness, convulsions, respiratory arrest and death. The detailed investigation of a patient with complaints after chronic exposure demonstrates the necessity of objective neurophysiologic studies. Acrylonitrile has carcinogenic properties in animals. It is also embryotoxic and teratogenic. Epidemiological studies in men exposed to acrylonitrile are not convincing. There may be a slight excess of deaths from lung cancers and other malignant tumors. Effects of potential antidotes were studied in animal experiments. Rats were intoxicated with lethal doses of acrylonitrile by different routes of application. The cyanide antidotes 4-dimethylaminophenol plus thiosulfate showed some protective effect only after oral but not after i.p. or inhalational acrylonitrile administration. Of the sulfhydryl compounds cysteine, N-acetyl-cysteine, cysteamine and diethyldithiocarbamate, the two antidotes cysteine and N-acetylcysteine proved to be especially effective. From these experiments a tentative schedule of antidotal therapy for humans accidentally intoxicated with acrylonitrile is inferred, using N-acetylcysteine by analogy with the therapeutic regimen effective in cases of paracetamol poisoning.

Acrylonitrile↗