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Biomedical subjects

A N Iavorskiĭ

Publications and source records attributed to A N Iavorskiĭ.

At least 19 recordsLinked to original sources
PubMed1995

[Vitamin A and enzyme systems of metabolic activation of genotoxic compounds].

The study was undertaken to study the effects of N-nitrosodimethylamine (NDMA) on the formation of single-strand DNA breaks and gamma-glutamyltransferase-positive knots, the status of the enzymatic systems involved in NDMA metabolism and some other biochemical parameters when rats were on retinol-deficient diets and when they were given excessive vitamin A. The action of retinol on NDMA effects were analyzed by evaluating the activity of glutathione-S-transferase (EC 2.5.1.18), glutathione-reductase (EC 1.2.1.1), aldehyde-dehydrogenase and aldehyde-oxidase (EC 1.2.1.3 and EC 1.2.3.1, respectively), p-450 reductase NADPH cytochrome (EC 1.6.2.4), the demethylase and hydroxylase activities, levels of malonic dialdehyde and the rate of ascorbate-dependent lipid peroxidation, the contents of proteins, phospholipids, cysteine, redox glutathione, glucuronides, sulfates. The level of vitamin A in the animals was found to substantially affect the magnitude of the genotoxic action of NDMA. The supplementary administration of vitamin A reduced the effect of the carcinogen. The mechanism of protective action of retinol was largely explained by the mediated activity of cytochrome-P-450 and glutathione-dependent systems involved in the biotransformation of NDMA. Based on the data available in the literature and their own data, the authors analyzed the effects of retinol on the metabolism of genotoxicants and described possible mechanisms of its antimutagenic and anticarcinogenic action. It is concluded that the effective protection of the body from unfavourable environmental influences may be provided only by supplementary (more than the optimum) intake of vitamin A against the background of a damaging factor.

Animals↗
PubMed1986

[Effect of cefuroxime on embryonic and fetal development in an experiment].

The direct and indirect effects of cefuroxime on the embryo and fetus were studied in vitro and in vivo at different gestation times. The placenta, liver and kidneys of the mother and fetus were investigated morphologically. It was shown that in a dose of 250 mg/kg the antibiotic did not induce disorders in the fetus development. The histological examination of the fetus placenta and liver revealed no changes as compared to the controls. However, in the renal tubules of the mother and fetus, pathological lesions in the form of the cytoplasm granular degeneration and nucleus swelling, lysis and necrosis were observed. These lesions were of a dose-dependent character. The possible nephrotoxic effect of cefuroxime prevents its use as a drug of choice in treatment of gestation pyelonephritis.

Abnormalities, Drug-Induced↗
PubMed1985

[Quantitative informational estimation of the degree of liver damage on a model of chronic alcoholic intoxication].

In the rat liver at a chronic alcoholic intoxication produced with various doses of ethanol, a double phased picture of informational characteristics has been revealed in the cellular nuclei under a linear increase of the dose. An analysis of corresponding distribution of the hepatocytic nuclei has been performed according to their size and informational characteristics. On this base, the limiting dose of ethanol is estimated for development of the hepatic alcoholic lesion.

Alcoholism↗
PubMed1980

[Reactivity of the hypothalamo-hypophyseal neurosecretory system of rats preferring and refusing alcohol].

Rats were kept for one and six hours in a thermal chamber at a temperature of -4 degrees C under conditions of free choice between 5% ethanol and water. Study of the morphological picture of the supraoptic and paraventricular nuclei of the hypothalamus and neurohypophysis of rats that preferred alcohol or rejected it has shown an inverse relationship between marked initial preference of alcohol and resistance of the hypothalamohypophyseal neurosecretory system of the animals to hypothermal exposure that exhausts the neurosecretory function.

Alcohol Drinking↗
PubMed1979

[Effect of phenazepam on the ethanol demand of rats].

The new Soviet tranquilizer phenazepam given to rats intraperitoneally at a dose of 1 mg/kg daily was shown to be capable of suppressing ethanol addiction produced by 2-month intake of 5% ethanolic solution as the only source of liquid. The mechanism of this effect is likely to be related to the changes in the activity of the neurosecretory centers of the hypothalamus. The phenazepam in the treatment of chronic alcoholism.

Alcohol Drinking↗
PubMed1979

[Embryotropic action of phenazepam in mini pigs, a new species of experimental animals].

It has been established in experiments on mini pigs of Siberian origin that phenazepam given at a dose of 1 mg/kg per os during organogenesis has no embryotoxic or teratogenic action. The drug content in the blood of pregnant animals was determined simultaneously. A conclusion is drawn about perspectiveness of using mini pigs for testing embryotoxic activity of drugs.

Animals↗
PubMed1979

[Effect of carbidine on the sex glands of rats chronically exposed to ethanol].

In experiments on rats it was shown that carbidine injected intramuscularly for two weeks does not effect gonadotropic action in a dose effective in experimental therapy of alcohol dependence (4 mg/kg). The drug neither potentiates adverse after-effects of chronic action of ethanol on ovo- and spermatogenesis nor slows down the course of the reparative processes in the gonads after ethanol is discontinued. However, further regressive changes in the gonadal generative elements were recorded in administering carbidine against the background of continued use of ethanol.

Alcoholism↗
PubMed1978

[Preventive effect of lithium chloride on the development in rats of a preference for ethanol].

It was revealed in experiments on rats treated with a 5% ethanol solution with equal quantities of LiCl (experiment) and NaCl (control) for seven weeks as the only source of liquid that with li+ concentration in the blood plasma of approximately 0.6 meq/1 LiCl prevented the development of alcohol dependence. On studying the neurosecretory hypothalamic nuclei, hypophysis and adrenal cortex of the same animals a certain correlation has been demonstrated between the morphofunctional condition of the mentioned formations, the degree of ethanol preference development and the character of LiCl influence on the process.

Alcoholism↗
PubMed1978

[Chronobiologic aspect of the mechanism of action of lithium salts in experimental alcoholism].

Ethanol, used for 2 months in a 5% solution, disorganized the circadian cycle of the hystophysiologic activity of the rat epiphysis. During prolonged (course) administration in the doses close to those used at the clinic lithium chloride normalized the mentioned changes and also prevented their development in case of joint two-months use of ethanol and lithium salt. This effect of the drug correlates with the inhibition or prevention of the ethanol preference development observed under these perimental conditions. A possible interrelationship between the discovered capacity of lithium salt to normalize the chronobiological derangements of the epiphysis and clinical efficacy of these salts in alcoholism and other affective periodical disorders is discussed.

Alcoholism↗
PubMed1977

[Effect of lithium chloride on ethanol uptake by rats].

A selective uptake of ethanol by presenting its 5% solution as the only source of fluid was elaborated in rats for 2 months. It was found that lithium chloride injected intravenously in a dose of 35 mg/kg twice per 24 hours for 14 days depressed the ethanol preference causing a motivation inversion whose mechanism was associated with the changes in the activity of the hypothalamic centres of the neuroendocrine regulation. A possibility of lithium salts in the therapy of chronic alcoholism is discussed.

Alcoholism↗
PubMed1977

[Effect of lithium chloride on the rat hypothalamus neurosecretory system].

Methods of quantitative cytochemical analysis were applied to the study of the reaction of the hypothalamohypophysial neurosecretory system (HHNS) to single and course administrations of lithium chloride (in doses of 200 mg/kg). Reaction of the HHNS proved to depend directly on the amount of lithium administered and was characteriaed by the activation of the synthesis and elemination of the neurosecretion with a single administration on the preparation, or depression of the hormonopoiesis in the hypothalamus and exhaustion of the neurosecretion stores in the neurohypophysis in its course application. During the restoration (7 to 30 days after stopping the drug administration) the state of the HHNS gradually approached the initial level. The authors came to the conclusion that the changes in the central mechanisms of the neuro-endocrine regulation at the hypothalamic level caused by lithium were significant in the pathogenesis of the side-action of its salts

Animals↗
PubMed1976

[Role of the kidneys in the pathogenesis of lithium poisoning].

Lithium intoxication was induced in rats by intraperitoneal administration of lithium chloride in a daily dose of 200 mg/kg (0.22 LD50) for 6 days. Polyuria connected with pathological changes in the epithelium of the convoluted tubules and depression of the antidiuretic hormone--acid mucopolysaccharides system in the area of the straight kidney tubules was observed on the 6th day of the experiments. Oligouria and death of some of the animals on the 7th experimental day was caused by severe lesions the kidney structure. Further observation (30 days) demonstrated that, along with the regeneration processes, there developed a marked sclerosing ofthe kidney tissue. A conclusion was drawn that severe lithium intoxication was associated with the development of acute renal insufficiency. Functional reserves of the kidneys after the cessation of lithium chloride administration remained lowered for a long period.

Acute Kidney Injury↗
PubMedDate not supplied

[Various mechanisms of the depriming effect of bacterial endotoxin on drug metabolism].

The effect of an endotoxin from Sh. Boydii on the biotransformation of amidopyrine and acetanilide, the activity of microsomal monooxygenases, hemoxygenase, and xanthine oxidase, the lipid peroxidation (LPO) intensity, the phospholipid spectrum, and the solubilization of microsomal membrane components was studied by intraperitoneal injections (2.5 mg/kg) in rats. It was found that the endotoxin inhibits the reactions of C- and N-acetanilide hydroxylation, N-amidopyrine demethylation, acetanilide hydrolysis at the amide bond, conjugation of aminophenol metabolites with glucuronic acid and sulfate, and 4-aminoantipyrine binding to acetate. The endotoxin effect reached maximum 24 h after injection and was observed for 96 h. The inhibition of metabolism of the test preparations is related to a decrease in the content of cytochrome P-450 and in the activity of 1A2, its 2B, 2C, 3A, and 2E1 isoforms. This is obviously caused by activated LPO and enhanced nitric oxide synthesis, as evidenced by a tenfold increase in the content of NO metabolites (nitrites and nitrates) in the blood of test animals. In clinical practice, it is necessary to take into account the possibility of a significant biotransformation of drugs in the acute period of bacterial infection, which may lead to changes in the pharmacological effect and toxicity of some drugs.

Acetanilides↗
PubMedDate not supplied

[Pathogenesis of lithium polyuria].

An attempt is made to elucidate the pathogenesis of polyuria arising consequent upon medication of affective states with lithium salts. Experiments conducted with 54 male-rats showed that changes in the neurosecretion of supraoptic nuclei of the hypothalamus and neurohypophysis that take place after a course-wise intraperitoneal administration in amounts of 200 mg/kg (2/9DL20) of lithium chloride per 24 hours for a duration of 6 days occur parallel with histochemical changes of renal acid muconpolysaccharides and they accord with the nature of diuresis disorders. By the 5th day of the experiment the compound perverts the antidiuretic effect of a single subcutaneous injection of pituitrin (10 U/kg). The authors infer therefrom that polyuria emerging after introduction of lithium salts is caused by a deranged synthesis and secretion of the diuretic hormone and also by the ability of lithium to mitigate the action of this hormone on the kidneys.

Animals↗
PubMedDate not supplied

[The prolonged use of calcium antagonists in myocardial infarct in rats: their effect on hemodynamics and the contractile function and morphology of the heart muscle].

Experiments on rats with myocardial infarction induced by occlusion of the left coronary artery were made to explore the influence of calcium antagonists injected intraperitoneally for a long time (daily, for 21 days) on hemodynamics, contractile function and morphology of the heart muscle. It has been shown that verapamil (0.5 mg/kg), diltiazem (2 mg/kg) and nimodipine (20 micrograms/kg) do not exert under those conditions any noticeable effect on pump and contractile heart functions. Administration of verapamil in a doze of 2 mg/kg enhanced heart failure. The drugs under study normalized the response of contractile heart function to volumetric load, which is related to a considerable measure to the acceleration of reparative processes in the myocardium.

Animals↗
PubMedDate not supplied

[The influence of modulators of enzyme activity on the pharmacological effect of thiopental sodium and ketamine and on the pharmacokinetics of thiopental sodium].

The rat experiments studied the impact of inductors and inhibitors of enzymatic activity of xenobiotic metabolism on the pharmacological activity of sodium thiopental and ketamine and on the pharmacokinetics of sodium thiopental. Cocarboxylase, cobalt chloride and cimetidine enhanced the pharmacological action of sodium thiopental, but failed to exert any action on the effect of ketamine. The preparations of vitamin K, particularly vikasol and menadione sodium bisulfite, and phenobarbital attenuated the effects of these anesthetics, but tocopherol unchanged it. Phenobarbital and vikasol accelerated blood elimination of sodium thiopental, whereas cimetidine and cocarboxylase slowed down this process.

Animals↗
PubMedDate not supplied

[Use of automatic cytophotometric analysis for assessing the hepatotropic action of ethanol].

It has been shown in experimental chronic intoxication that there is a close correlation between the dose of ethanol, microscopic appearance of the liver, the content of DNA, RNA, protein, glycogen in hepatocytes and structural parameters of nuclear chromatin of these cells. It is concluded that automatic cytophotometric analysis of the structure of hepatocyte nuclei holds promise for an accurate quantitative evaluation of the hepatotropic action of chemical substances and drugs.

Alcoholism↗