Enterosorption as an approach to the elimination of chronic endotoxin aggression

Examination of 25 patients with chronic inflammatory diseases (in remission) has shown that enterosorption can considerably decrease the total concentration of bacterial lipopolysaccharide in the systemic blood flow.     

Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with unfavourable outcomes in patients with acute coronary syndrome

We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10 G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we determined that patients with CAD diagnose and A alleles gene IL10 had unfavorable outcome more often than patients with homozygous G alleles. Survival time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p = 0.042). The group studied do not differ significantly with respect to the distributions of gene IL6 G(-174)C alleles and genotypes. However in case combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C polymorphism we determined that patients with CAD diagnose and carrier genotype GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23, p = 0.017. The obtained data allows assuming the important role of the IL6 and IL10 genes which are responsible for functioning of inflammation system, in the accelerated formation of failures at the patients who had a coronary syndrome.     

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol–chloroform extraction by the standard method. IL6 −572 G/C, IL12B 1159 C/A, and IL10 –627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 −627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 −572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 −627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 −627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.     

The polymorphisms G(−174)C in IL6 gene and G(−1082)A in IL10 gene are associated with poor outcomes in patients with acute coronary syndrome

Association between the rates of poor outcomes in the patient cohort with acute coronary syndrome and polymorphisms G(?174)C in the IL6 gene and G(?1082)A in the IL10 gene were determined. In total, 1145 patients hospitalized for coronary artery disease to cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don were examined. The mean observation period was 9.10 ± 5.03 months (maximal, 18 months). Analysis of the survival of the patients with acute coronary syndrome that carried allele A has demonstrated that the presence of IL10 gene polymorphism G(?1082)A is associated with more frequent poor outcomes as compared with GG genotype. The survival time to endpoint for the carriers of GA and AA genotypes was 11.68 ± 0.67 months versus 12.69 ± 0.65 months for the carriers of GG genotype in IL10 gene (χ² = 4.13, p = 0.042). As for the IL6 gene polymorphism G(?174)C, survival rate analysis did not detect any significant association with the risk for poor outcome. However, joint analysis of these polymorphisms in both genes has demonstrated that characteristic of the patients with acute coronary syndrome that carry GG genotype of IL6 gene and GA and AA genotypes of IL10 is a higher rate of poor outcomes (time to endpoint, 11.01 ± 1.24 months) as compared with the carriers of IL6 gene CC and CG genotypes and IL10 gene GG genotype (time to endpoint, 13.28 ± 0.83 months (ξ² = 10.23, p = 0.017). These data suggest that the genes IL6 and IL10, whose products are involved in the control of inflammatory response, play an important role by increasing the probability of poor outcomes in the patients with acute coronary syndrome.     

P-(Alkyl)-Nucleoside 5′-Hydrogenphosphonates as Depot Forms of Antiviral Nucleotide Analogues

Abstract

P-(Alkyl)esters of AZT 5′-hydrogenphosphonate were synthesized and their stabilities in the phosphate buffer and human serum were evaluated. The esters bearing residues of primary and secondary alcohols were degraded to give AZT, whereas those containing tertiary alkyl groups yielded AZT 5′-hydrogenphosphonate. The corresponding derivatives of d2A and d4T showed the same properties.     

Role of the antioxidant system in response of Escherichia coli bacteria to cold stress

The response of aerobically grown Escherichia coli cells to the cold shock induced by the rapid lowering of growth temperature from 37 to 20 degrees C was found to be basically the same as the oxidative stress response. The enhanced sensitivity of cells deficient in two superoxide dismutases, Mn-SOD and Fe-SOD, and the increased expression of the Mn-SOD gene, sodA, in response to cold stress were interpreted as both oxidative and cold stresses are due to a rise in the intracellular level of superoxide anion. The long-term cultivation of E. coli at 20 degrees C was also accompanied by the typical oxidative stress response reactions--an enhanced expression of the Mn-SOD and catalase HPI genes and a decrease in the intracellular level of reduced glutathione (GSH) and in the GSH/GSSG ratio.     

Mechanical stimulation of the support zones of soles: The method of noninvasive activation of the stepping movement generators in humans

The effects of mechanical stimulation of the soles’ support zones in the modes of slow and fast walking (75 and 120 steps per minute) were studied using the model of supportlessness (legs suspension). 20 healthy subjects participated in the study. EMG activity of hip and shin muscles was recorded. Kinematics of leg movements was assessed with the use of videoanalysis system. In 80% of cases support stimulation was followed by leg movements, in 69% of which they had characteristics of locomotions being accompanied by the burst-like electromyographic activities. The order of involvement of leg muscles and organization of antagonistic muscles activities were analogous to those of voluntary walking. The latencies of electromyographic activity in hip and shin muscles composed 5.17 ± 1.08 and 14.01 ± 2.82 s, respectively, the frequencies of bursts differed significantly depending on stimulation frequency. In 31% of cases the electromyographical activity following the stimulation of the soles’ support zones had not burst-like but uninterrupted pattern. Its amplitude rose smoothly reaching a certain level that was subsequently maintained. Results of the study showed that soles’ support zones stimulation in the mode of locomotion could activate a locomotor generator provoking the appearance of locomotion-like activity and that effect evoked by this stimulation includes not only rhythmical but also non-rhythmical (probably postural) components of walking.     

A method of selective derivation of the action potentials of human motor units through surface electrodes

The results of the development of methods for selective recording of the potentials of motor units of human arm, leg, and head skeletal muscles through surface electrodes are described.     

Polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene and association with unfavorable outcomes of coronary atherosclerosis in patients with a history of acute ischemic heart disease

The polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene were tested for association with the frequency of unfavorable outcomes in patients with a history of acute ischemic heart disease. The study involved 1145 patients hospitalized in cardiology clinics of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don because of acute ischemic heart disease. The patients were followed up for up to 62.5 months. None of the markers displayed a significant association with the time to an endpoint. The patients were then grouped by sex. In females, the frequency of unfavorable outcomes (fatal or nonfatal myocardial infarction and fatal or nonfatal stroke) was higher in carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and carriers of genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene, but the difference was not statistically significant. Such an increase in frequency was not observed in males. To study the combined effect of the polymorphic markers of the THBD and F7 genes, the course of ischemic heart disease was compared for two female subgroups. One included carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene; the other subgroup included carriers ofgenotype Ala/Ala of the Ala455Val polymorphic marker of the THBD gene and allele Gln of the Arg353Gln polymorphic marker of the F7 gene. The frequency of unfavorable outcomes in the first subgroup was higher than in the second one. The time to an endpoin was 40.5 months (95% confidence interval (CI) 33.5-47.6) in the first subgroup and 51.6 months (95% CI 45.0-58.1) in the second subgroup (chi2 = 4.15, P = 0.042). The results made it possible to assume that the F7 and THBD genes play an important role in genetic predisposition to unfavorable outcomes in patients with a history of acute ischemic heart disease.