Biomedical subjects
Publications and source records attributed to O O Pentiuk.
The analysis of clinical, laboratory and instrumental data allows to elaborate the method of complication appearance prognosis in patients with acute cholecystitis.
A comparative evaluation was done of efficacy and safety of methotrexate, leflunomide singly and of combination of methotrexate with leflunomide or detralex. A total of 189 patients with rheumatoid arthritis (RA) were examined. A 6-month course of controllable treatment was instituted in them. The time-related course of clinical-and-laboratory indices allowed judgement about efficiency of the treatments administered. The functional condition of the patients was assessed according to HAQ. As to efficacy and toxicity, leflunomide (in a dose of 20 mg/daily) was comparable to methotrexate (7.5 to 10 mg/per week) whereas the combination leflunomide-methotrexate has been shown to considerably accelerate regression of clinical symptoms of RA while the use of detralex in the therapeutic complex proved to enhance efficiency of pharmacotherapy with methotrexate and to reduce the incidence rate of its side effects.
Results of the study of homocysteine metabolism and its role in physiological and pathological processes are given in this review. The participation of homocysteine in the process of methionine synthesis, transsulfuration, formation of homocysteine thiolacton and their regulation, polymorphism of homocysteine metabolism enzymes, the ways of homocysteine and thiolactone incorporation into protein molecule, sources and forms of homocysteine in the blood plasma, the role of hyperhomocysteinemia in pathogenesis of cardiovascular and other diseases have been considered. Principles of homocysteine determination in the blood plasma are described here.
In experiments on 205 rats it was fixed, that starvation during 2-3 days, as well as introduction of acetone (250 and 1000 mg/kg) considerably increases CYP2E1-dependent aniline and p-nitrophenol hydroxylase activity in the liver, kidneys, lungs and CYP3A dependent erythromycin N-demethylase activity, at the same time, suppress in a liver activity enzymes, dependent CYP2D, CYP1A2 and CYP2C as well as of activity UDP-glucuronosyl-transferase, sulfotransferase and glutathione-S-transferase. The starvation causes accumulation of KoA and increases activity of N-acetyltransferase in the liver. Starvation induces the change of enzymes activity and correlates with the intensifying of the processes of lipolysis, glycogenolysis, gluconeogenesis and, especially, ketogenesis which are appreciably initiated by introduction of acetone. The starvation and introduction of acetone increases metabolism of acetanilide and brombenzene, and, increasing the formation of toxic metabolites, raise its hepato-, nephro- and pulmotoxicity. The starvation attenuates elimination of indometacin from blood plasma, but intensifies conjugation of sulfadimidine with acetic acid.
The role of cytochrome P4502E1 in metabolism of substances, polymorphism, ways of the expression regulation, change of activity in pathological condition is considered in the review. Cytochrome P4502E1 catalyzed first two reactions of acetone transformation in the lactic acid, ethanol oxidation, metabolism of fatty acids and their hydroperoxides. Cytochrome P4502E1 dependent metabolism of xenobiotics in many cases results in formation of toxic intermediates and radicals of oxygen. Regulation of cytochrome P4502E1 expression includes transcriptional mechanisms and substrate stabilization of its molecule. The enzyme activity grows in alcoholism, diabetes mellitus, obesity, steatohepatitis, administration of acetone, alcohols and is connected with intensification of toxicity of paracetamol, halothane, benzene, tetrachlororomethane and others xenobiotics. Such inhibitors of cytochrome P4502E1 as dialyl sulphide, disulfiram have hepatoprotective action.
In the present study we determined the age-related effect of methionine-enriched diet, a model of hyperhomocysteinemia, on the level of plasma homocysteine and hepatic global DNA methylation in rats. Feeding methionine diet to middle-aged rats for only 14 days resulted in a significant increase in plasma homocysteine level and DNA hypomethylation. In contrast, feeding the methionine-containing diet for 2 weeks to juvenile or post-pubertal animals did not alter the level of plasma homocysteine or hepatic DNA methylation. Supplementation of the methionine-enriched diet with vitamins B6, B12 and folic acid prevented both hepatic DNA hypomethylation and an increase of plasma homocysteine concentration in the middle-aged rats. These findings indicate that the elevated level of plasma homocysteine may be indicative of much broader and deeper alterations in intracellular methylation dysfunction, and suggest that dietary enrichment with B-vitamins is essential for the metabolism of homocysteine, especially in adult animals.
The non-narcotic analgetic benzofurocaine in intravenous administration at the dose level of 300 mg exerts an apparent analgesic effect in those patients with various pathogenetic mechanisms of the pain syndrome. The pharmacologic effect of the drug depends upon its blood plasma content. The character of the interrelationship is described by hysteresis curve suggesting the pharmacologic effect to be behind the time of building up of maximum blood drug concentration. The pharmacokinetic determinants of the analgesic action of benzofurocaine are the area under the pharmacokinetic curve, half-life period, and average time of drug retention in blood. There is a close direct correlation between the above determinants.
Demethylation kinetics of analgetics tramal, benzofurocain and amidopyrine has been studied through the experiments on microsomal fraction of white rats' liver. It was found that tramal demethylation is apparently catalysed with the help of two enzymes, possessing various affinities towards the substrate. Kinetics of benzofurocain and amidopyrine demethylation is satisfactory described with the help of Michaelis-Menten equation. Cimetidine, thiamine diphosphate and orthophen (at concentrations close to therapeutic ones) exhibit mixed-type inhibition in respect of all three demethylaze substrates under study.
The alimentary tocopherol deficiency is accompanied by decreased hydroxylase, demethylase, NADH- and NADPH-reductase, aldehyde dehydrogenase, arylesterase and glutathione reductase activity in rat's liver. It decreased the reduced glutathione and increased it's oxidized form concentration in the tocopherol deficient animals. The stability of microsomal membrane is decreased to solubilizing action of deoxycholate and trypsin. This changes, possibly, caused elevation of alteration of function enzyme's and microsomal membrane after nitrosodimethylamine (NDMA) administration in deficient rats. The 7-days injection of tocopherol (20 and 100 mg/kg), dibunol (80 mg/kg), sodium selenite (30 mkg/kg) increased aldehyde dehydrogenase, esterase, glutathione-dependent enzymes activity and increased of reduced glutathione concentration in liver, suppressed lipid peroxidation and increased survival rats after lethal dose carcinogen treatment. Supplementation of tocopherol decreased harmful action of nitrosodimethylamine on microsomal membrane and enzymes activity.