[Association of the polymorphisms of the FTO, KCNJ11, SLC30A8 and CDKN2B genes with type 2 diabetes].

To study the association with diabetes mellitus type 2 we performed anal- ysis of the distribution of frequencies of alleles and genotypes of polymorphic markers of FTO, KCNJ11, SIC30A8 and CDKN2B genes. The study included groups of T2DM patients and unrelated controls of Russian origin. Analysis of the distribution of frequencies of alleles and genotypes of the polymorphic markers of KCNJ11, SLC30A8 and CDKN2B genes showed the presence of association with T2DM in Russian population, while for the FTO gene was not found statistically significant associations with type 2 diabetes. We can conclude that in Russian population main role in the development of type 2 diabetes play genes, affecting the level of syn- thesis and secretion of the insulin in beta-cells of the pancreas.

[Oxidative stress in pathogenesis of bronchial asthma: a method of correction by inhalation of phospholipid nanoparticles].

The authors present the results of a prospective simple blind randomized placebo-controlled study for the evaluation of dynamics of biomarkers of oxidative stress (total concentration of nitrate- and nitrite-anions in condensed exhaled breath and plasma, pH of exhaled breath, total antioxidative activity of plasma in patients with bronchial asthma inhaling phospholipid nanoparticles. The results suggest significant positive effect of proposed therapy on dynamics of the main parameters of oxidative stress including reduced concentration of nitric oxide metabolites and increased total antioxidative activity of plasma. No clinically significant reactions were documented.

[Ergoferon and oseltamivir in treatment of influenza: results of multicentre randomized comparative clinical trial].

The narrow range of choice and virus resistance to the most common drugs require search and introduction of new drugs with proven efficacy and safety for the treatment of influenza. Ergoferon is a new combined medicine containing release active antibodies to interferon-gamma (anti-IFNgamma), CD4-coreceptor and histamine. The formulation influences various links of antiviral defense and provides antiinflammatory effect. The efficacy of the drug is related to its production process during which multiple reduction of the initial concentration of every component leads to release of special release activity. Previous experimental studies showed that anti-IFNgamma had antiviral activity against pandemic influenza virus A (H1N1) 2009 comparable to that ofoseltamivir (suppression of virus replication in the lung tissue, increase of the lifespan and reduction of the laboratory animals mortality). The aim of the multicentre randomized clinical trial was to compare (versus oseltamivir) the efficacy and safety of ergoferon in the treatment of influenza in adults. 213 patients with flu-like symptoms were examined in 8 medical centres of Russia during two epidemiological seasons (2010-11 and 2011-12). The inclusion criteria were: the first 48 hours after the onset; fever > or =37.8 degrees C, at least one common symptom and at least one respiratory symptom. Influenza was confirmed in 52 patients by QuickVue rapid diagnosis. 23 patients received ergoferon according to the treatment scheme and 29 received oseltamivir (daily dose 150 mg). Duration of the treatment was 5 days. The patients were followed up for 7 days. The primary endpoint was the percentage of the patients with the body temperature normalization for 2-5 days of the treatment. The maximum efficacy of ergoferon was observed on the second day of the treatment: almost half (48%) of the initially febrile patients had normal body temperature (versus 28% in the patients treated with oseltamivir). The comparison of the two groups of the patients by the morning and evening measurements of the body temperature every five days of the treatment by Cochran-Mantel-Haenszel revealed a significant difference between the two groups (chi2 = 7.1; p = 0.008). The average duration of the fever in the group of ergoferon was 2.3 +/- 1.2 days, in the group of oseltamivir--2.6 +/- 1.3 days (the efficacy of oseltamivir in the present study was comparable with the previously published data). The percentage of the patients treated with antipyretics because of hyperthermia on the second day of the treatment lowered 3 times and amounted to 17% (versus 41% in the oseltamivir group). The severity of common and respiratory symptoms (nose/throat/chest) significantly decreased on the third day of the treatment in both groups, the majority of the patients had either minimum severity or no signs of influenza. The clinical improvement was associated with positive changes in the life quality. No cases of the disease aggravation were recorded. Complications requiring antibiotic treatment or hospitalization were not observed during the followup. There were no adverse events recorded due to the drug use. No deviations in the laboratory indices were stated. Ergoferon is a new safe drug for the treatment of influenza. Its clinical efficacy was comparable to that of oseltamivir. The therapeutic effects of the drug were evident from: significant reduction of the disease severity, duration of febricity and general toxicity and respiratory flu symptoms, lower percentage of the patients with fever for 2 days. The febrile period in most of the patients did not exceed 2 days.

[Experience with the use of phospholipid preparations in the combined treatment of bronchial asthma].

The authors report the results of a single-blind randomized placebo-controlled study of the efficacy and safety of inhalation of phospholipid nanoparticles in patients with bronchial asthma. They give evidence of the statistically significant positive effect of the proposed therapeutic modality on the clinical status of the patients and lung functional tests. No clinically significant adverse events were documented during the study.

[Preparation and characterization of the recombinant protein containing immunomimetic peptide of benzo[a]pyrene].

Two recombinant plasmids were constructed. The first plasmid contained the hybrid gene composed of immunomimetic peptide of benzo[a]pyrene, of the protein pIII of bacteriophage M13 and of cellulose binding domain encoding sequences. The second plasmid contained the hybrid gene composed of the signal peptide of the protein pIII of bacteriophage M13, of immunomimetic peptide of benzo[a]pyrene, of the protein pill of bacteriophage M13 and of cellulose binding domain sequences. The obtained recombinant plasmids were used in expression of chimeric protein containing immunomimetic peptide ofbenzo[a]pyrene based on strain E. coli M15. The lack of the recombinant protein expression using first plasmid was demonstrated. In the same time, it was shown that accumulation of recombinant protein contained immunomimetic peptide with signal peptide of the protein pIIIl of bacteriophage was present. This chimeric protein was produced in "mature" (without signal peptide) and "unprocessing" (with signal peptide) forms. Using the Western-blot analysis, it was shown that the "mature" form only specifically bound to the B2 monoclonal antibody against benzo[a]pyrene. Thus, we expressed, purified, and characterized the recombinant protein containing immunomimetic peptide of benzo[a]pyrene.

[Phenotypes of patients with chronic obstructive pulmonary disease].

AIM: To study characteristics of phenotypes of chronic obstructive pulmonary disease (COPD) basing on the findings of modern clinical, functional and roentgenomorphological tests in the course of the disease. MATERIAL AND METHODS: Basing on the results of high performance computed tomography, 64 COPD patients aged 46-75 years (FEV1 51 +/- 24%) were divided into two groups: 53 patients with emphysematous phenotype (group 1) and 11 patients with bronchytic phenotype (group 2). The groups were compared by constitutional, clinical, functional and roentgenological parameters. RESULTS: Group 1 patients had significantly less body mass index, more severe edema by Borg's scale, low FEV1, FEV1/FLC, diffuse lung capacity and lung tissue density compared to group 2. Bronchoectases occurred more frequently in group 1 (33 and 9%, respectively). CONCLUSION: Heterogenous COPD phenotypes differ not only at the stage of chronic respiratory insufficiency but also at all stages of the disease.

[Isolation of intact supercoiled mitochondrial DNA from the yeast Saccharomyces cerevisiae]. / Vydelenie intaktnoi kol'tsevoi superspiralizovannoi mitokhondrial'noí DNK drozhzheí-sakharomitsetov.

Cells of Saccharomyces cerevisiae strain PG-60 were mechanically disrupted in the presence of ethidium bromide, and the total covalently closed circular DNA (ccDNA) was prepared by EthBr-CsCl equilibrium centrifugation of lysed 15 g pellet of the homogenate. Recentrifugation of ccDNA in equilibrium neutral CsCl density gradient resolved a discrete light peak (LccDNA) with the buoyant density equal to 1.684 g/cm3 to about 10% of total ccDNA. Electron microscopy has shown that LccDNA contained circular molecules with the contour length around 25 micrometer circles and their multimeres. Well characterized linear mtDNA was transcribed with E. coli RNA-polymerase and cRNA obtained was hybridized with LccDNA 2 mu DNA and total DNA from yeast petit mutant, lacking mtDNA. Hybridization experiments have shown that the transcript of mtDNA hybridized almost exclusively with LccDNA. We have concluded that 25 micrometer circles of the LccDNA represent intact molecules of yeast mitochondrial DNA.

[RNA biosynthesis and regulation of protein biosynthesis in the liver of chicks with experimental coccidiosis]. / Biosintez RNK i reguliatsiia biosinteza belkov v pecheni tsypliat pri éksperimental'nom koktsidioze.

The aim of this work was to investigate the interrelationship between RNA biosynthesis and that of protein in chick liver during experimental coccidiosis induced by E. tenella. The peculiarity of this model is that in the course of this disease protein synthesis is significantly intensified inspite of the fact that the rate of the biosynthesis is rather high under normal conditions. It has been shown that 4 to 6 days after infection incorporation of labeled amino acids into proteins from chick liver subcellular fractions is greatly increased. The most pronounced changes are in ribosomal and mitochondrial fractions as well as in the postribosomal supernatant. At the same time the specific radioactivity of serum albumin excreted by liver was increased by factor 3. These changes in protein biosynthesis are associated with a significant increase of both the content and intensity of biosynthesis of high molecular weight precursors of rRNA as well as with those of mature 18S rRNA. The amount of 28S rRNA and mRNA per cell is practically without any changes whereas the mRNA turnover is somewhat more extensive. The selective accumulation of 18S rRNA is suggested to be responsible for the intensification of protein biosynthesis.

[Changes in RNA biosynthesis in the liver of chicks with coccidiosis]. / Izmeneniia biosinteza RNK v pecheni tsypliat pri koktsidioze.

The RNA fraction and the intensity of their turnover in chick liver during experimental coccidiosis was studied. A marked (about 60%) increase of intensity of mRNA turnover with no changes in its amount was found. It was shown that pre-rRNA biosynthesis was significantly enhanced and, due to it, the amount of both pre-rRNA and mature 18S rRNA was increased while the level of 28S rRNA was unchanged. The relations between the observed changes of RNA biosynthesis and protein biosynthesis in liver in coccidiosis as well as the role of these changes in pathological process studied are discussed.