[POLYMORPHISM OF CYP2C9 GENE AND RISK OF HEPATOTOXICITY DEVELOPMENT DURING ANTIRETROVIRAL THERAPY.]

We have studied the association of polymorphic variants of CYP2C9 genes with the risk of drug-induced liver injury (DILI) during antiretroviral therapy of HIV-infected patients. The analysis of polymorphic variants of CYP2C9*2.(Argl44Cys) and CYP2C9*3 (Ile359Leu) genes showed that the dominant genotype of CYP2C9*2 was the honiozygous CC carriership and for CYP2C9*3 it was the prevalence of AA genotype, the incidence of which was close and amounted to 80%. There was no association of these genotypes CYP2C9 with the risk of DILI. Thus, the carriership of individual C and T alleles in the case of CYP2C9*2 gene, as well as A and C for CYP2C9*3 is not a predictor of antiretroviral DILI.

[Mesenchymal stem cells as perspective method of fibrosis/cirrhosis treatment].

UNLABELLED: THE PURPOSE OF THE REVIEW: Discuss the background and available results of transplantation of bone marrow stem cells as a promising treatment of hepatic fibrosis. KEY PROVISIONS: Actuality of the problem of chronic hepatitis is present due to their progressive course with the formation of liver cirrhosis and a high level of mortality. Conservative treatment of patients with decompensated process requires a liver transplantation that is compounded by the high percentage of graft reinfection in infectious hepatology. It is necessary to study the use of bone marrow-derived stem cells transplantation, because MSCs have certain therapeutic potential, low immunogenicity and the capacity for directional migration. In experimental models MSCs mechanisms of action are shown to limit the progression of liver fibrosis and stimulation of regeneration processes. In clinical studies good tolerability and relative safety of administration of autologous MSCs have reported as well as the positive effects on liver synthetic function, a decrease in the severity of cirrhosis on class Child-Pugh and MELD, reduction in overall mortality are shown. The results of our own prospective pilot study using autologous MSCs from bone marrow in patients with HCV-associated liver cirrhosis are described. CONCLUSION: MSCs can exert multiple synergistic effects on the hepatic stellate cells, reduce inflammation in the liver tissue remodeling processes and fibrogenesis. For objective evidence of the clinical benefits of the method, evaluation of long-term efficacy and safety of MSCs, as well as developing rational strategies, further clinical studies are required.

[Differential diagnosis of and diphtheria and tonsillitis]. / Differentsial'naia diagnostika angin i difterii.

Differential diagnostic differences have been analyzed for faucial diphtheria (41 patients), infectious mononucleosis (219 patients), follicular and lacunar tonsillitis (71 patients), Vincent tonsillitis (22 patients). Besides specific clinical manifestations, of special importance in distinguishing the above diseases was a profound analysis of hemogram with calculations of special parameters and variants of ESR/leukocyte count ratio.

[Correction of disorders in the monooxygenase system function with diethylnicotinamide (cordiamine) in tetrachloromethane- induced and viral hepatitis]. / Korrektsiia diétilnikotinamidom (kordiaminom) narusheniia funktsii monooksigenaznoi sistemy pri tetrakhlormetanovom i virusnom gepatitakh.

Content of cytochromes P-450 and b5 and the rate of oxidative dealkylation in liver microsomes as well as the antipyrine pharmacokinetics were normalized in rats with acute CCl4-induced hepatitis after treatment with cordiamine (diethyl nicotinamide) at a dose of 40 mg, subcutaneously, 2 times daily within 4 days. Cordiamine (30 drops 3 times daily within 8 days) contributed to normalization of the hydroxylating reaction in liver tissue of patients with viral hepatitis A, estimated by the "antipyrine" test. The drug exhibited stabilizing effect on hydrophobic interactions in microsomal membranes; diethyl nicotinamide possessed antiradical and vitamin properties.

[Lipostabil in the treatment of viral hepatitis B in subjects who abuse alcohol]. / Lipostabil v lechenii virusnogo gepatita B u lits, zloupotrebliaiushchikh alkogolem.

A trial was conducted of clinical efficacy of lipostabil. Twenty-three lipostabil-treated patients with hepatis B abusing alcohol were compared to a control group receiving standard treatment. Lipostabil has advantages as it shortens jaundice, cholestasis, enhances recovery of lipid metabolism in erythrocytic membranes and antioxidant properties of blood. Lipostabil holds promise in multimodality treatment of combined hepatic lesions.

[The characteristics of the immune response during the development of hepatitis B against a background of chronic alcoholic liver lesions]. / Osobennosti immunnogo otveta pri razvitii gepatita B na fone khronicheskikh alkogol'nykh porazhenii pecheni.

In two groups of patients with viral hepatitis B (100 patients in each group) the comparative evaluation of immune response was carried out on the basis of the results obtained in the study of the duration of the presence of HBsAg in the blood, the time of the primary appearance of anti-HBsAg antibodies, cell-mediated and humoral immunity characteristics. The study revealed the aggravating influence of alcohol on the outcome of hepatitis B, manifested by the prolonged circulation of HBsAg, decreased antibody formation and T-immunosuppressive deficiency, which was linked with defective immune response in hepatitis B patients with disposition to the excessive use of alcohol.

[Diethylnicotinamid (cordiamine) stabilization of the liver hydroxylating function in rabbits with CCl4 poisoning]. / Stabilizatsiia diétilnikotinamidom (kordiaminom) gidroksiliruiushchei funktsii pecheni krolikov pri otravlenii CCl4.

Three and ten days after the administration of CCl4 (subcutaneously, once, 4 ml/kg of 50% oil solution) there were found a decrease of the rate of antipyrine elimination (intravenously, 50 mg/kg) from the blood plasma, an increase of the total bilirubin content, ALT activity and stimulation of lipid peroxidation processes. Cordiamine administration (subcutaneously, twice a day, 3 and 10 days) exerts the normalizing effect.

[The effect of diethylnicotinamide (cordiamine) on the activity of the hydroxylating and glucuronyl-conjugating systems in humans]. / Vliianie diétilnikotinamida (kordiamina) na aktivnost' gidroksiliruiushchei i gliukuronilkon''iugiruiushchei sistem u liudei.

Administration of diethylnicotinamide (250 mg orally three times for 8 days) to healthy subjects increased antipyrine (AP) elimination from the saliva by 23% and decreased its half-life by 26%. The excretion in the urine of the products of AP hydroxylation 3-carboxymethylantipyrine and nor-antipyrine as well as glucuronides 3-hydroxymethylantipyrine increased. A positive correlation between the dynamics of the excretion of antipyrine metabolites and glucuronic acid was observed. The elimination from blood of bilirubin glucuronides increased. Diethylnicotinamide in therapeutic doses is supposed to stimulate the processes of hydroxylation and glucuronyl conjugation in humans.

[Changes in the fatty acid composition of erythrocyte membranes in patients with chronic alcoholism under the effect of a diet enriched with linoleic acid]. / Izmeneniia zhirno-kislotnogo sostava membran éritrotsitov u bol'nykh khronicheskim alkogolizmom pod vliianiem ratsiona, obogashchennogo linolevoi kislotoi.

The authors have studied the influence of additional introduction into the ration of sunflower oil on fatty-acid composition of erythrocytic membranes in chronic alcoholics. The computerized discriminant analysis has evidenced that additional introduction of sunflower oil into the ration of the patients normalizes the fatty-acid spectrum of erythrocytic membranes. Besides that, enrichment of the ration with linoleic acid improves the parameters characterizing the liver function (bilirubin, alanine aminotransferase of blood serum).

[Effectiveness of phenobarbital, ziksorin and cordiamine in the treatment of non-conjugated hyperbilirubinemia]. / Effektivnost' fenobarbitala, ziksorina i kordiamina v lechenii nekon'iugirovannoi giperbilirubinemii.

The effectiveness of phenobarbital, ziscorine, cordiamine and the combination of phenobarbital and pyrogenal was studied in 48 patients with non-conjugated hyperbilirubinemia. In effectiveness the agents were distributed in the following order: cordiamine, phenobarbital, ziscorine. The combination of phenobarbital and pyrogenal has proved to be inexpedient.

[Pharmacokinetics of antipyrine in viral and alcoholic lesions of the liver]. / Farmakokinetika antipirina pri virusnom i alkogol'nom porazhenii pecheni.

Parameters of antipyrine pharmacokinetics have been studied in 82 patients with viral, alcoholic and combined liver affections and in 19 healthy subjects. All the patients exhibited changes showing a reduction of liver function responsible for drug metabolism. Disturbances of antipyrine pharmacokinetics were more pronounced in acute alcohol-aggravated hepatitis B than in hepatitis B without alcoholic aggravation.