[Regulating activity of plasma membranous Ca2+ channels in PC-12 pheochromocytoma cells with chemicals and pharmaceutic agents]. / Reguliatsiia aktivnosti Ca2+-kanalov plazmaticheskikh membran kletok feokhromotsitomy PC-12 s pomoshch'iu khimicheskikh soedinenii i farmakologicheskikh agentov.

The activity of the voltage-operated Ca2+ channels (VOC channels) and store-operated Ca(2+)-channels (SOC channels) was studied on rat pheochromatocytomic cells PC-12 by using the fluorescence calcium dye Fura-2. The VOC channels were transferred in their open state by depolarizing the plasma membranes of the cells through addition of high KCl concentrations (50 mM). The SOC channels were activated by treating the cells with tapsigargine, a special inhibitor of Ca2+ ATPase in the intracellular Ca2+ stores. Verapamil effectively inhibited the activity of the VOC channels (IC50 = 0.6 micron), but failed to affect the SOC channels. Arachidonic acid reduced the level of [Ca2+]-induced TG (200 nM) at a concentration of 3-10 microns). The movement of Ca2+ along the SOC channels was electrogenic. The depolarization of the plasma membrane of PC-12 cells caused no release of Ca(2+) from the intercellular Ca2+ stores. It is concluded that PC-12 cells are a suitable model to study the activity of different Ca2+ channels and search for chemical compounds that affect the potential-dependent and potential-independent Ca2+ channels.

[A preclinical evaluation of the pharmacological activity of a mixed potassium and magnesium glutamate]. / Doklinicheskaia otsenka farmakologicheskoi aktivnosti smeshannogo glutamata kaliia i magniia.

Mixed magnesium and potassium glutamates with different ion ratio are synthesized. The antiarrhythmic activity of the compounds obtained is studied on the models of strophantin, calcium chloride, aconitine arrhythmia, and arrhythmia after Harriss. It is found that magnesium and potassium glutamate of the composition KMg(HGlu)4.4H2O exhibits higher activity compared to glutamate of the composition KMg(HGlu)4.3H2O on the strophantin and calcium chloride arrhythmia models. The study performed on the strophantin and calcium chloride models as well as on the Harriss arrhythmia model showed that KMg(HGlu)4.4H2O is more effective as antiarrhythmic drug than asparkam and panangine but, at the same time, the effect of KMg(HGlu)4.4H2O within the aconitine model is somewhat less pronounced compared to panangine.

[The effect of sodium nitroprusside and nitro-containing vasodilators on rat liver microsomal mono-oxygenases]. / Vliianie nitroprussida natriia i nitrosoderzhashchikh vazodilatatorov na mikrosomnye monooksigenazy pecheni krys.

It has been shown in vitro that sodium nitroprusside (SN) causes a concentration-dependent suppression of the enzymatic activity of aminopyridine demethylase-APDM(IC50 = 1.86 x 10(-4) M) and ethoxycoumarin O-deethylase-ECOD(IC50 = 1.46 x 10(-4) M) in hepatic microsomes of Wistar rats, which is related to different isoforms of cytochrome P-450. The inhibiting effect of other nitro compounds (nitroglycerin and isosorbide dinitrate) in relation to APDM is less marked than that of SN. These compounds have practically no effect on ECOD activity. It is assumed that the degree of the inhibiting effect of SN, nitroglycerin, and isosorbide dinitrate is connected with the mechanism of NO release.

[The pharmacological properties of coenzyme A disulfide]. / Farmakologicheskie svoistva kofermenta A-disulfida.

Coenzyme A disulfide (CoA disulfide) was pharmacologically studied. It has been found to normalize lipid and carbohydrate metabolism when given in a dose of 2 mg/kg, i.m., in diverse liver dysfunctions. It possesses an antihypoxic action under hemic and histotoxic hypoxia. When given in small doses (80-160 micrograms/kg, i.v.), CoA disulfide depresses the function of cellular hemostasis.

[The metabolism and biological activity of glucuronidation substrates in experimental diabetes mellitus]. / Metabolizm i biologicheskaia aktivnost' substratov gliukuronidirovaniia pri éksperimental'nom sakharnom diabete.

The study was undertaken to examine the impact of experimental diabetes mellitus on the biotransformation of some drugs, their toxicity and hypoglycemic action, as well as on the biotransformation of endogenous testosterone and the androgenic status. The accelerated metabolism of both exogenous and endogenous substrates which occurred in diabetes mellitus caused a decrease in their biological activity.

[A metabolic study of the synthetic glucocorticosteroids prednisolone and dexamethasone in the body of white rats and in in-vitro reactions]. / Izuchenie metabolizma sinteticheskikh gliukokortikosteroidov prednizolona i deksametazona v organizme belykh krys i v reaktsiiakh in vitro.

The metabolism of the synthetic steroidal hormones prednisolone and dexamethasone was studied in albino rats and in in vitro microsomal oxidation system by using high performance chromatography and radioactive tracers. Dexamethasone was found to be metabolically stable. The first step of prednisolone biotransformation is formation of prednisone during the NADPH-dependent reaction catalyzed by microsomal enzymes. Conditions were created for isolating the ultimate prednisolone metabolite formed in the rats' body by using HPLC.

[Drug derivatives of xanthine]. / Lekarstvennye sredstva--proizvodnye ksantina.

The data on the pharmacological effects of xanthines and their use in pharmacotherapy, particularly, in regulation of cellular hemostasis to correct disorders of microcirculation are summarized. The possible mechanisms of hemostasis regulation by xanthines and the most promising ways of search for new antiaggregation drugs in this series are considered.

[The dynamics of prednisolone and dexamethasone distribution and metabolism in the body of white rats]. / Dinamika raspredeleniia i metabolizm prednizolona i deksametazona v organizme belykh krys.

The processes of elimination and distribution of the synthetic steroidal drugs prednisolone and dexamethasone in the internal organs of Wistar rats were studied by the method of radioisotopes and high performance liquid chromatography. It was shown that the main route of excretion is the elimination with the urine. Prednisolone does not undergo conjugation and dexamethasone is glucuronidated by approximately 20%. The conclusion is made about the dependence of the main pharmacokinetic parameters on the concrete route of metabolism of each drug.

[Methodologic problems of pharmacokinetics]. / Metodologicheskie problemy farmakokinetiki.

The subject of pharmacokinetics, method of research, aims and tasks of fundamental and applied aspects, place and importance for pharmacology are discussed. Discrepancy between a high scientific potential of pharmacokinetics and a low practical realization are analyzed, priority trends of future research are formulated.

[Change in carbohydrate metabolism, secretion of insulin and glucagon in normoglycemic rats during administration of various doses of nicotinamide]. / Izmenenie uglevodnogo obmena, sekretsii insulina i gliukagona u normoglikemicheskikh krys pri vvedenii razlichnykh doz nikotinamide.

Development of hypoglycemia, a slight decrease in concentration of glucagon in blood as well as increase in activity of malate-and glucose-6-phosphate dehydrogenases in liver cytosol were detected in rats injected subcutaneously with nicotinamide at a dose of 31.25 mg/kg 6 hrs before decapitation. Increase of the single dose up to 125 mg/kg caused hypoglycemia, distinct increase in concentration of insulin and glucagon in blood plasma simultaneously with a pronounced inhibition of the enzymatic activity in liver tissue. Effect of nicotinamide on carbohydrate metabolism appears to have a dissimilar character depending on the drug dose: its small doses accelerated utilization and oxidation of glucose but did not affect the secretion of insulin and glucagon.

[Effect of nicotinamide on body glucose utilization in animals]. / Vliianie nikotinamida na utilizatsiiu gliukozy organizmom zhivotnykh.

A single administration of nicotinamide (62.5 mg/kg) was found to enhance the relative activity of exogenous insulin, to decrease glucose level in the peripheral blood, to increase the activity of malate dehydrogenase and glucose-6-phosphate dehydrogenase in the liver cytosol in intact mice and to increase the rate of exogenous glucose utilization in rabbits. The character of nicotinamide effect on carbohydrate metabolism in intact animals is suggested to be dose-dependent. When administered in low doses, the drug increases tissue sensitivity to endo- and exogenous insulin.

[Metabolic products of methandrostenolone in the body of white rats studied by high-performance liquid chromatography]. / Izuchenie produktov metabolizma metandrostenolona v organizme belykh krys metodom vysokoéffektivnoi zhidkostnoi khromatografii.

Metabolism of the anabolic steroidal hormone methandrostenolone in Wistar rats was studied by high performance liquid chromatography (HPLC) and redioisotope techniques. The conditions for isolation of methandrostenolone metabolites by HPLC were developed. Reduction of the double bonds was shown to be an early stage in methandrostenolone biotransformation. The main portion of the metabolites was excreted with urine as glucuronide conjugates. No sulfoesters were found.

[Dynamic distribution of methandrostenolone in the body of white rats]. / Dinamika raspredeleniia metandrostenolona v organizma belykh krys.

Dynamics of distribution of anabolic steroidal hormone methandrostenolone and routes of its elimination from the organism of Wistar rats were studied by using methods of radioisotopes and high-performance liquid chromatography. Methandrostenolone metabolites were shown to be excreted mainly in the urine. Methandrostenolone metabolism is a complicated process in the course of which redistribution of metabolites among various organs occurs. The anabolic effect of methandrostenolone is supposed to be due to the formation of its metabolites.

[Hormonal metabolic status of the human body under the conditions of the Far North]. / Gormonal'no-metabolicheskii status organizma cheloveka v usloviiakh Krainego Severa.

The concentrations of hormones (ACTH, cortisol, aldosterone, thyrotrophin, thyroxine, triiodothyronine, growth hormone, insulin, prolactin and testosterone), electrolytes (Na and K) as well as glucose and triglycerides were measured in 10 athletes who made a 380 km ski expedition in the Far North at ambient temperatures of -32 to -34 degrees C. Human adaptation to the geographic and climatic conditions of high latitudes was accompanied by noticeable changes in the incretory function of the adenopituitary, thyroid gland, adrenals and gonads. The data obtained indicate that a ski trip in the Far North produces a distinct stress with physical and cold components being predominant.

[Microbiological method of determining cyanocobalamin in tissues and finished drugs made from animal raw materials]. / Mikrobiologicheskii metod opredeleniia tsianokobalamina v tkaniakh i gotovykh lekarstvennykh sredstvakh iz zhivotnogo syr'ia.

An assay for cyanocobalamin with the use of the test microorganism E. coli, mutant ATCC 9637, is offered. The measurement of the content of cyanocobalamin in the blood serum and liver of intact rats after intraperitoneal drug injection demonstrated its content to reach a maximum 30 minutes after injection and to depend on the dose. When given in doses 100 and 400 micrograms/kg, the drug dose in the serum amounted to 82 and 261 ng/g, respectively, and in the liver to 80 and 259 ng/g. The method is readily reproducible, does not require the observance of strict aseptics, it is economical and time-saving.