[Effect of dimethicone on pharmacokinetics and pharmacodynamics of ethyl biscoumacetate]. / Effet du diméticone sur la pharmacocinétique et la pharmacodynamie du biscoumacétate d'éthyle.

The influence of dimeticone (Gel de Polysilane Midy) on the pharmacokinetics and pharmacodynamics of oral ethyl biscoumacetate was studied in 6 healthy volunteers in a randomised single dose, two-way cross-over study. Each volunteer received at one week interval a single dose (300 mg) of ethyl biscoumacetate, either alone or with dimeticone. Ethyl biscoumacetate levels were measured in plasma for 24 hours. Pharmacodynamic parameters were measured for 96 hours. Ethyl biscoumacetate peak concentration was significantly higher when administered with dimeticone (40.3 +/- 25.3 mg/l vs 31.0 +/- 25.7 mg/l; p = 0.031), without significant change in the area under curve. Other pharmacokinetic and pharmacodynamic parameters did not differ significantly. The slight increase of the ethyl biscoumacetate bioavailability with dimeticone in repeated dosing might have pharmacodynamic consequence; a clinical trial should address this question.

Phytomenadione improves red cell deformability in laboratory animals.

The deformability of red blood cells (RBC) is one of the factors that determine whole blood rheology. Derivatives of vitamin K (phytomenadione, menadione, menadione bisulfite) are electron-transporting substances. The aim of this study was to investigate the possible influence of derivatives of vitamin K on erythrocyte deformability in studies in vivo--on rats and rabbits. The influence of vitamin K antagonist on erythrocyte deformability (ethylbiscumacetate) was also determined. Pentoxifylline known to affect RBC deformability was also included in the study as the control treatment. The study was performed on white laboratory rats and domestic rabbits. The blood was obtained from animals after single and multiple dosing of drugs. Blood sample was prepared and RBC filterability was assayed with a gravity driven filtration technique. Pentoxyfylline did not change erythrocyte deformability after single dose, but significantly improved erythrocyte deformability of laboratory animals after multiple application. Filterability values of the RBCs of the rats and rabbits increased significantly after single and multiple treatment with phytomenadione, while the two other derivatives, menadione and menadione bisulfite, did not change RBC deformability. Ethylbiscumacetate did not change erythrocyte deformability in rats after single dose.

[The effect of vicasol and pelentan on the biopolymers of the periodontium]. / O vliianii vikasola i pelentana na sostoianie biopolimerov periodonta zubov.

Vitamin K (vikasol) and pelentan were examined for their effects of periodontal tissue levels of collagen, hexosamine-containing biopolymers and sialoglycoproteins. During tooth replantation in dogs, vitamin K was demonstrated to elevate the levels of collagen, hexosamine-containing polymers in periodontal tissue by 25.8, 19.9, and 36.1%, respectively, whereas pelentan lowered the above parameters.

[Status of liver mitochondria and rat tissue creatine kinase during administration of antivitamin K]. / Sostoianie mitokhondrii pecheni i aktivnost' kreatinkinazy tkanei krysy pri vvedenii antivitamina K.

It has been shown that 16-18 days administration of antivitamin K (pelentan) leads to two-fold increase of prothrombin time in adult rats but does not influence the soluble brain, renal, heart, muscle and serum creatine kinase activity. No effect on metabolic function of isolated liver mitochondria has been found in contrast to the vitamin K deficient rats. Mitochondria were characterized by high value of respiration control; substance oxidation rates and internal mitochondrial Ca2+ content do not differ in the level from those of control animals. From the obtained results and data published in literature a conclusion can be drawn about only particular similarity (prothrombin time) between the antivitamin K administration and alimentary vitamin K deficit.

[Metabolic function of isolated liver mitochondria during various conditions of vitamin D and K supply and administration of pelentane]. / Metabolicheskie funktsii izolirovannykh mitokhondrii pecheni pri razlichnoi obespechennosti krys vitaminami D i K i vvedenii pelentana.

Alimentary deficiency of vitamin K caused a decrease in the rate of respiration in presence of ADP and in the rate of oxidative phosphorylation in the presence of succinate. Administration of the antivitamin K pelentane, excess of vikasol and deficiency of vitamin D did not affect these parameters. As distinct from controls and rats treated with pelentane, transport of calcium was decreased in presence of all the substrates studied in mitochondria isolated from liver tissue of animals deprived of vitamins K and D as well as of animals treated with vikasol excess. At the same time, accumulation of calcium led to time-dependent inhibition of respiratory chain if NAD-dependent substrates were used. Possible reasons of dissimilarity observed are discussed; the phenomenon found may occur due to exhaustion of the mitochondrial pyridine nucleotides pool. The data obtained suggest that antivitamins K altered only some parameters of body status (prothrombin time) similarly to the alterations observed in alimentary deficiency of vitamin K.

[The effect of supplying rats with vitamin K and administration of pelentane on Na,K- and spectrin-dependent ATPase in erythrocyte ghosts]. / Vliianie obespechennosti krys vitaminom K i vvedeniia pelentana na Na,K- i spektrinzavisimuiu ATPazy tenei éritrotsitov.

It was found that the activity of spectrin-dependent ATPase of erythrocyte ghosts isolated from rats with alimentary deficiency of vitamin K was significantly increased as compared with control animals, whereas in rats kept on a vicasol-rich diet this parameter was unchanged. In vitamin K-deficient rats the amount of proteins loosely bound to erythrocyte membranes was significantly reduced. At the same time, the activity of the integral enzyme (Na, K-ATPase) did not depend on the vitamin K provision despite the fact that in vitamin K-deficient animals kept on a vicasol-rich diet the enzyme affinity for ouabain was strongly decreased as compared with control. It was suggested that this effect might be due to the changes in the lipid and protein environment of the membrane-bound enzyme. Administration of the antivitamin K, pelentane, did not induce any conspicuous changes in the enzyme activities. It was concluded that antivitamin K does not induce any modification of the properties of erythrocyte-linked enzymes observed under conditions of vitamin K deficiency.

[Metabolism of the inhibitor of fibrin self-assembly in rats]. / Obmen ingibitora samosborki fibrina u krys.

It has been shown that the application of the labelled preparation in physiologically normal white rats and in animals with experimental hyper- and hypothrombinemia leads to the rapid exchange of the peptide self-assembly inhibitor between the blood and extravascular space. The constant level of the inhibitor in the blood is maintained due to continuous supply from tissues and its excretion with the urine. The role and mechanisms of the inhibitor involvement into the maintenance of the liquid state of the blood as a factor limiting the speed of nonenzymatic stage of fibrinogen conversions are suggested.

[Mechanism of action of hydroxycoumarin derivatives]. / K mekhanizmu deistviia proizvodnykh oksikumarina.

Experimental and clinical studies have demonstrated the effects of hydroxycoumarin derivatives (pelentan) on the composition and correlation of phospholipids (PL) in red cell biomembranes. PL such as cardiolipin, cholesterol and its esters phosphatidylethanolamine, and phosphatidylcholine experienced the greatest changes. The changes in the composition of biomembrane PL were accompanied by an increase in the total cholesterol content in red cell biomembranes and by an increase in the total and free non-esterified fatty acids in blood plasma (P less than 0.05). At the same time the changes were discovered in the activity of transketolase and glucose-6-phosphate dehydrogenase limiting the pentosephosphate shunt.

[Allosteric regulation of glucosamine synthetase activity by naphthoquinone derivatives and ethyl ester of di-(4-oxycumarinyl-3)-acetic acid]. / Allostericheskaia reguliatsiia aktivnosti gliukozaminsintetazy proizvodnymi naftokhinona i etilovym efirom di-(4-oksikumarinil-3)-i uksusnoi kisloty.

The effects of derivatives of naphthoquinone, e.g. 2-methyl-3-phytyl-1,4-naphthoquinone (vitamin K1), 2-methyl-1,4-naphthoquinone (vitamin K3), 3-dihydro-2-methyl-1,4-naphthoquinone-2-sodium sulfonate (vicasol), derivatives of naphthohydroxyquinone, e.g. 2-methyl-1,4-naphthohydroxyquinone 1-monoacetate, 2-methyl-1,4-naphthohydroxyquinone 1,4-diacetate and the oxycumarine derivative di-(4-oxycumarinyl-3)-acetate ethyl ester (pelentan) on the activity of purified glutamine synthetase (EC 5.3.1.19) from rat liver were studied. The enzyme activity was increased under effects of vitamins K1 and K3 and was inhibited by pelentan. The data obtained are indicative of the allosteric effect of these compounds on the enzyme.

[Role of the liver in producing heat-stable antifactor Xa]. / Rol' pecheni v produktsii termostabil'nogo antifaktora Xa.

The thermostable antifactor Xa is demonstrable in liver homogenate extracts in an amount exceeding its content in other parenchymatous organs and blood serum. In the course of liver perfusion and incubation of liver sections, the antifactor is demonstrable in the perfused liquid and in the medium used for incubation. Affection of the liver with carbon tetrachloride was attended by the decreased content of the antifactor in serum. The liver seems likely to play an important role in the production of the thermostable antifactor Xa.

[Immunosupressant activity of direct and indirect acting anticoagulants]. / Immunodepressornaia aktivnost' antikoaguliantov priamogo i nepriamogo deistviia.

Indirect action anticoagulants, when injected into (CBA--C57BL) F1 mice in doses commensurable with human therapeutic doses, produced different immunotropic effects: acenocoumarin and pelentan had no influence on the formation of immune response, whereas omephin showed a considerable stimulating effect on this process. Large doses of acenocoumarin, pelentan and omephin inhibited the formation of immune response if the antigen was introduced immediately after the injection of the anticoagulant. The immunosuppressing action of pelentan was particularly pronounced. Heparin suppressed the formation of immune responsèe both in imediate and delayed immunization. In immediate immunization the immunosuppresing action of heparin and pelentan injected simultaneously was weaker than the action of heparin alone. Small doses of pelentan haod no influence on the remote effect of heparin, whereas large doses of pelentan abolished the immunosuppressing action of heparin in delayed immunization.

The effects of menadione, ethyl biscoumacetate, and sodium salicylate on the metabolism of mucopolysaccharides in the aortic wall and liver of rats.

In rats with hyper- and hypovitaminosis the contents were determined of acid mucopolysaccharides (MPS) on the basis of contents of hexuronic acids; the total contents of biopolymers containing hexosamines (acid MPS, glycoproteins), on the basis of contents of hexosamines in the aortic wall and in the liver; and the activity of glutamine-fructose-6-phosphate aminotransferase (GPAT; EC 2.6.1.16) in the liver. Menadione-induced K hypervitaminosis was accompanied by moderate elevations of indicators of MPS metabolism. Protracted administration of ethyl biscoumacetate or sodium salicylate lowered the contents of acid MPS and of biopolymers containing hexosamines in the aortic wall and in the liver. Simultaneously, the GPAT activity in the liver markedly decreased.