[Comparative evaluation of the action of oxythiamine and its derivatives on animals with Erhlich's ascitic cancer]. / Sravnitel'naia otsenka deistviia oksitiamina i nekotorykh ego proizvodnykh na zhivotnykh s astsitnym rakom Erlikha.

It is found that hydroxythiamine ester with sebacic acid surpassed hydroxythiamine in its antitumour effect on Ehrlich ascites tumour in albino mice. A linear correlation is observed between the values of activity coefficients of hydroxythiamine and its esters with dicarboxylic acids and some morphometric data.

[Comparative antivitamin activity of oxythiamine disulfide and its monosulfoxide]. / Sravnitel'naia antivitaminnaia aktivnost' oksitiamindisul'fida i ego monosul'foksida.

The B1-antivitamin activity of oxythiamine disulphide monosulphoxide has been determined in experiments on albino mice. It is shown that this derivative is less toxic and exerts a more profound and prolonged inhibitory action on the pyruvate dehydrogenase and transketolase activity in the animal body in comparison with initial oxythiamine disulphide.

[Transketolase inhibitors based on disulfide derivatives of oxythiamine with branched hydrocarbon chains]. / Ingibitory transketolazy na osnove disul'fidnykh proizvodnykh oksitiamina s razvetvlennymi uglevodorodnymi tsepiami.

The experiments on mice have shown that oxythiamine disulphide derivatives with the branched hydrocarbon chains are less toxic in the organism as compared to oxythiamine and corresponding disulphides with the unbranched hydrocarbon chains and also induce a more pronounced inhibition of transketolase in the liver and other tissues. It is found that under the effect of the above substances the recovery of enzymic activity is slower than in the case with the oxythiamine application.

[Antivitamin activity of O-acyloxythiamine disulfides]. / Antivitaminnaia aktivnost' O-atsiloksitiamindisul'fidov.

B1-antivitamin activity of symmetrical oxythiamine disulphide esters with succinic and o-phthalic acids has been studied in experiments on albino mice. It is shown that O-acyloxythiamine disulphides exert more profound and prolonged inhibitory effect on the transketolase activity in the animal body in comparison with the known antagonist of vitamin B1, oxythiamine, and the initial oxythiamine disulphide.

[Optimization of hydroxythiamine administration regimen in vitaminological research]. / Optimizatsiia rezhima ispol'zovaniia oksitiamina v vitaminologicheskikh issledovaniiakh.

A correlation between the different doses and inhibitory effect of hydroxythiamine relative to the activity of main thiamine pyrophosphate-dependent enzymes is studied in experiments on animals. It is established that the maximal inhibitory effect on the transketolase and oxoglutarate dehydrogenase activities is at a dose of antivitamin of 0.35 mmol/kg and that of pyruvate dehydrogenase of 0.55 mmol/kg. At lower doses of hydroxythiamine the inhibition of enzyme activities occurred in a dose-dependent manner.

[Effect of thiochrome capronate on lipid metabolism in rats]. / Vliianie tiokhromkapronata na obmen lipidov u krys.

Thiochrome caproate modified by the oxyethyl radical of the thiochrome derivative was studied for its effect on different indices of lipid metabolism in the liver and blood of albino rats. It was shown that when animals were fed on a standard laboratory diet, thiochrome caproate changed the amount of total and free fatty acids in the studied tissues and the fatty acid composition in the liver to a greater extent than thiochrome and hydroxythiamine.

[Features of thiamine diphosphate-dependent enzyme inhibition by oxodihydrothiochrome and its phosphorylated derivatives]. / Osobennosti ingibirovaniia tiamindifosfatzavisimykh fermentov oksodigidrotiokhromom i ego fosforilirovannymi proizvodnymi.

Anticoenzyme action of new derivatives of thiamine: oxodihydrothiochrome and its mono- and diphosphoric esters has been studied in the experiments on mice. It is shown that the given compounds exert an inhibiting action on transketolase and pyruvate dehydrogenase and do not change activity of 2-oxoglutarate dehydrogenase in the animal organism. Antivitamin effect of the studied inhibitors is observed with the lower doses and in the earlier terms as compared with the other known inhibitors of thiamine-diphosphate-dependent enzymes. The preparations inhibit activity of the yeast pyruvate-decarboxylase by the mixed (with respect to thiamine-diphosphate) type (Ki for oxodihydrothiochrome and its mono- and diphosphoric esters: 2.3 x 10(-3), 7.2 x 10(-4), 5.6 x 10(-5) M, respectively). Possible mechanisms of the action of the mentioned compounds as thiamine antimetabolites are discussed.

[Advantages of oxythiamine bromide as a specific inhibitor of activity of thiamine-dependent enzymes]. / Preimushchestva oksitiaminbromida kak spetsificheskogo ingibitora aktivnosti tiaminzavisimykh fermentov.

Production of hydrogen bromide salt of hydroxythiamine (Ht. HBr) from thiamine bromide was developed its toxic and inhibitory properties towards transketolase and pyruvate dehydrogenase were studied as compared with commercial preparation hydroxythiamine chloride (HT. HCl). As compared with HT. HCl, synthesis of HT. HBr was more simple, the higher yield and purity of the end product were achieved. At the same time, the preparation was less toxic and exhibited the antivitaminous activity similar to the commercial chloride form.

[Changes in the permeability of the blood-brain barrier to oxythiamine]. / Ob izmenenii pronitsaemosti gematoéntsefalicheskogo bar'era dlia oksitiamina.

Activity of transketolase was distinctly inhibited in mice brain after simultaneous administration of hydroxythiamine and 3,3-dimethyl-l-phenyl-l-phthalyl acetic acid. The rate of the enzyme inhibition correlated with an increase of the acid concentration in the mixture studied. The data obtained suggest that permeability of blood-brain barrier for hydroxythiamine was altered in simultaneous administration of the vitamin with some biologically active preparations.

[Specific activity of thiamine and oxythiamine immobilized on modified cellulose]. / Izuchenie spetsificheskoi aktivnosti immobilizovannykh na modifitsirovannoi tselliuloze tiamina i oksitiamina.

The effect of thiamine and oxythiamine preparations on the activities of vitamin B1-dependent enzymes in the body of white mice was studied. It was found that the cellulose oxythiamine derivative was similar to the initial compound in the character and intensity of its antivitamin action. It was also shown that the cellulose thiamine derivative had a prolonged effect in the body, which was manifested in a slower increase in the activities of transketolase, pyruvate dehydrogenase and in the amount of thiamine diphosphate in tissues of vitamin B1-deficient animals, as compared to the effect of thiamine.

Thiamine deficiency as predisposition to, and consequence of, increased alcohol consumption.

It was found that the activity of the marker thiamine-dependent enzyme, transketolase (TK), was decreased (down to 61-79% of control) in blood, liver and brain of inbred rats following a 6-month consumption of 15% ethanol as their only source of drinking fluid. After ethanol withdrawal, the enzyme activity was gradually restored, but did not reach the control values until 1 month following cessation of alcohol consumption. Moreover, in rats preferring ethanol, the decrease of TK activity was more pronounced than in water-preferring rats. Another experiment showed that thiamine deficiency induced by the thiamine antagonist, oxythiamine (200 mg/kg), led to a prolonged increase of the preferential intake of ethanol solutions in inbred rats. Significantly lower liver TK activities and thiamine pyrophosphate content were found in Finnish AA line rats as opposed to ANA line rats which had been obtained by selective outbreeding for high and low voluntary alcohol intake, respectively. Significantly lower TK activity was also found in the whole brain (89%), cerebellum (79%) and pons-medulla oblongata (87%) of AA rats as compared to ANA animals. Our own findings and the literature data confirm the hypothesis that thiamine deficiency can be both predisposing to and a consequence of, increased alcohol consumption.

Thiamine status in liver and brain of rats genetically selected for different sensitivity to hypnotic effect of alcohol.

BACKGROUND: The mechanisms of the different sensitivity or resistance of animals and humans to alcohol are still not completely understood. For further biochemical characterization of animals genetically selected for high-alcohol sensitivity (HAS) and low-alcohol sensitivity (LAS) with the hypnotic effect of alcohol, the thiamine status and thiamine metabolizing enzymes in these animals have been studied. METHODS: We investigated thiamine diphosphate and thiamine triphosphate levels as well as the activity of thiamine-dependent enzyme, transketolase, and thiamine-metabolizing enzymes, thiamine kinase, and thiamine triphosphatase in the liver and brain of HAS, LAS, and CAS (control) rats by standard biochemical techniques. RESULTS: It was found that the activity of transketolase, and the level of the coenzyme form of thiamine, thiamine diphosphate (TDP), were significantly lower in HAS versus LAS rats. The activation of transketolase by the exogenous TDP (TDP-effect) was significantly higher in the liver and brain regions of HAS rats compared with LAS rats. The level of TDP in the liver and cerebellum of HAS rats was significantly lower compared with LAS rats. These results indicate a severe deficiency of TDP in HAS rats. HAS rats have a significantly lower activity of thiamine triphosphatase, the additional source of TDP. Accordingly, HAS rats have much higher thiamine triphosphate levels in the liver and brain, compared with LAS rats. There were no significant differences between groups with respect to the thiamine diphosphatase and thiamine kinase activity. Most of the above parameters had the intermediate values in CAS rats, compared with LAS and HAS rats. These data indicate the possible role of the thiamine phosphate esters and related enzymes in the mechanisms that bring about the differential sensitivity to the hypnotic effect of alcohol. CONCLUSIONS: HAS rats have the genetically mediated thiamine diphosphate deficiency and increased thiamine triphosphate levels, probably due to reduced activity of thiamine triphosphatase in the liver and brain, compared with LAS rats. It can be related with the higher initial sensitivity of HAS rats to hypnotic effect of ethanol.

[Selective inhibition of pyruvate dehydrogenase in the liver and heart of mice by triphosphate esters of thiochrome and tetrahydrothiamine]. / Izbiratel'noe ingibirovanie piruvatdegidrogenazy pecheni i serdtsa myshei trifosfornymi éfirami tiokhroma i tetragidrotiamina.

In experiments with white mice it was shown that in contrast to hydroxythiamine and other known vitamin B1 antagonists, triphosphate esters of thiochrome and tetrahydrothiamine possess a selective anticoenzyme activity with respect to the only one of the thiamine pyrophosphate-dependent enzymes, i.e. pyruvate dehydrogenase.

[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes]. / Fermentnye sistemy substratnogo i kofaktornogo obespecheniia giperlipogeneza pri insulinnezavisimom diabete.

Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.