The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension

The levels of plasma interleukin 6 and its soluble receptors were found to be elevated in subjects with cardiovascular diseases, which points to amplification of the IL-6-mediated trans-signaling pathway in cells and the development of chronic inflammation. The allelic variation in the rs2228145 IL6R gene is associated with a change in the contents of the soluble and membrane-bound receptor forms mediating the biological activity of IL-6. Cytokine IL-6 is involved in the development of endothelial dysfunction by regulating the expression of the VCAM1 and ICAM1 genes, encoding intercellular adhesion molecules. Prior to this work, no data on the association of essential arterial hypertension (EAH) with rs2228145 allelic variations of the IL6R gene have been reported. The aim of our work was to study the relationship of the carriership of rs2228145 (A &gt; C) allelic variations with the development of EAH and the VCAM1 and ICAM1 transcript levels. We analyzed samples of DNA isolated from the whole blood of 148 healthy donors and 152 patients with EAH (stages I-II). The genotyp-ing was performed by PCR-RFLP. The level of transcripts in peripheral blood leukocytes (PBL) was assessed by real-time PCR. Differences in the frequency distributions of rs2228145 (A &gt; C) genotypes between the control group and the group of patients with EAH (χ2 = 9.303) were found. The frequency of the CC genotype in EAH patients was higher than in healthy people (0.191 and 0.095, respectively). The risk of EAH (I-II stages) development was shown to be 2.3 times higher in CC genotype carriers as compared to individuals with other genotypes (OR = 2.257, 95 % confidence interval 1.100-4.468). The levels of VCAM1 and ICAM1 gene transcripts in PBL of patients with EAH were significantly higher than in healthy people. The level of ICAM1 gene transcripts was almost 4 times higher in patients with CC genotype. The Kruskal-Wallis analysis of variance revealed an effect of rs2228145 (A &gt; C) genotype on the transcriptional activity of ICAM1, which argues for its role in the pathogenesis of endothelial dysfunction and essential hypertension

Impact of Cultivating Environment on the Terms of Persistence and Certain Properties of Cholera Vibrios

Objective of the study is to investigate the impact of cultivating temperature and medium on the terms of persistence, ctx gene retention, and enzymatic activity of V. cholerae O1 with various toxigenicity.Materials and methods. Utilized were the strains of V. cholerae El Tor: P-5879, P-19613, and also the strain P-19787.Results and conclusions. In the process of studying cholera vibrios El Tor with different genetic characteristics it was determined that the longest terms of persistence (19 days) on mineral substrates at 5 ºC were observed for toxigenic strains, while for non-toxigenic ones it made less than 17 days. At the same time cholera vibrios can persist continuously and even reproduce on mineral substrates under the conditions of subnormal lowered temperatures (not less than 10 °C). Toxigenic strains of Vibrio cholerae, irrespectively of cultivating medium and temperature, retained ctx gene in their genome and maintained enzymatic activity throughout the experiment. Such long-term persistence of cholera vibrios at low temperatures on mineral substrates may be regarded as possibility of preservation of V. cholerae toxigenic strains in case of import by the infected persons or vibrio-carriers

Features of parameters of cellular immune depending on the activity of foci of demyelination in children with multiple sclerosis

MS is a common disease of the central nervous system that leads to disability and reduced quality of life. The debut of disease in 3-5% of patients occurs in childhood and has a less favorable course compared to adults. MS is caused by the activation of autoreactive T cells in the breakdown of peripheral tolerance, which is normally controlled by regulatory T cells (Tregs). It is promising to study expression of CD39 and CD73 in Treg and Th17 populations to assess their suppressive activity. Aim is to evaluate content of major and minor lymphocyte populations and expression of CD39 and CD73 in CD4+ lymphocyte population in children with MS. 111 children with MS were examined, 66 with contrast-negative lesions on MRI (Group 1), 45 with contrast-positive lesions (Group 2). The comparison group consisted of 46 healthy children (Group 3). Content of T, B, NK lymphocytes, Treg (CD4+CD25highCD127low), Thact (CD4+CD25highCD127high), Th17 cells (CD3+CD4+CD161+); expression of CD39 and CD73 in Treg, Th17 and Thact was performed by flow cytometry. An increase in content of T helpers, a decrease in NK cells in patients in group 2 was revealed. An increase in number of Thact and Th17 lymphocytes was obtained in patients of both groups with MS. Number of Tregs in group 1 was significantly higher than in group 3. Ratio of cells expressing CD39 and CD73 in MS patients depended on lymphocyte population as well as in the group 3. The highest content of CD39+ cells was observed in Treg population, and the lowest in Thact population. For CD73 expression, on the contrary, the highest expression of CD73 was observed in Thact cells, the lowest in Treg. When comparing groups of patients, it was found that in patients of group 1, number of cells expressing CD39 ectonucleotidase was significantly increased, and number of supTh17 was comparable with group 3. In both groups of MS patients, an increase in CD73 counts in Treg, Thact and Th17 was observed. Thus, informative populations of lymphocytes (CD4+ cells, Treg, CD39+Treg, supTh17) have been identified, which can be used to monitor condition of children with multiple sclerosis

Nuclear transcription factor kB (NF-kB) activity in lymphocyte populations in children with Wilson-Konovalov disease

Wilson's disease (WD) is a rare hereditary disease caused by a deficiency of the ATF7B transporter. The accumulation of copper can cause damage to organs and cells, mainly the liver. Copper exposure can modulate cytokine synthesis through molecular and cellular signaling pathways, including the nuclear transcription factor NF-kB pathway. NF-kB is the main regulator of inflammation and cell death, acts as a central link between liver damage, fibrosis and hepatocellular carcinoma. An excess of NF-kB-dependent cytokine response stimulates inflammatory reactions, but excessive inhibition of NF-kB can negatively affect the viability of hepatocytes. Method of flow cytometry with visualization — Amnis ImageStreamX allows to evaluate the activity of NF-kB (% of activated cells in cell populations). The aim: to evaluate the activity of NF-kB in lymphocyte populations in children with WD disease. Immunophenotyping of lymphocytes and assessment of the level of translocation of NF-kB were performed in 52 children with WD and in 25 children of comparison group. The mass concentration of copper in daily urine was determined by atomic absorption method using the AAnalyst 800 spectrometer. In children with WD, the content of cells with NF-kB translocation varied from 5 to 90% depending on the lymphocyte population; the highest level was detected in B cells — 57.5 (37-68) %. A significant difference in distributions of the number of cells with NF-kB translocation between WD and healthy children was shown (F-criterion, p &lt; 0.01). In most cases, children with WD are characterized by a decrease in the activity of NF-kB in populations of B cells (in 43% of cases), T helper cells (48%), T cytotoxic (44%) and Th17 lymphocytes (41%). In children with WD, the concentration of copper varied from 9.7 to 2582 mcg/day, Me = 616 (210-1173). A direct relationship was obtained between the copper content in urine and the level of translocation of NF-kB in B lymphocytes, r = 0.34, p = 0.016. The activity of the NF-kB correlates with biochemical markers of the severity of liver damage (ALT, AST, GGT) and with copper content in urine. The study of the NF-kB signaling pathway seems promising for a better understanding of the pathogenetic mechanisms of the formation of inflammation and liver fibrosis in children with WD

Risk factors associated with default from multi- and extensively drug-resistant tuberculosis treatment, uzbekistan: a retrospective cohort analysis.

The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010

Контролируемые исследования по эффективности поликомпонентной вакцины при иммунотерапии у больных с хроническими обструктивными заболеваниями органов дыхания

During the hard controlled study, the effeciency of polycomponent vaccina designed by SRI of I.I.Mechnikov was investigated. The satisfactory and excelent effect was found in 71.4% of patients, that expressed in the listening of remission, the decrease of the exacerbation frequency and the severity of the disease course, the decrease of the quantity of medication, the improvement of respiration. Vaccina therapy induces the increase of the level of antibodies to all the antigen components of the vaccina in the patients. The number of patients with low titres of the antibodies decreases and the number of patients with high ones increases. Vaccina therapy with VP-4 used in according to the offered medication scheme does not induce the increase of the total IgE level in serum. There is the sharp decrease of this parameter in patients with the initial high level of IgE.В строго контролируемом опыте изучена эффективность поликомпонентной вакцины НИИ ВС им. И.И. Мечникова. Установлен хороший и отличный терапевтический эффект у 71,4% больных, что выражается в удлинении сроков ремиссии у больных, снижении частоты обострений и тяжести течения заболевания, сокращении количества принимаемых лекарств, улучшении показателей функции внешнего дыхания. Вакцинотерапия вызывает у больных подъем уровня антител ко всем антигенным компонентам вакцины. Уменьшается число больных с низкими титрами и увеличивается количество больных с высокими титрами антител. Вакцинотерапия ВП-4 по предложенной схеме введения не вызывает подъем уровня общего иммуноглобулина Е в сыворотке крови больных. У больных с исходно высоким уровнем иммуноглобулина Е отмечается выраженное снижение этого показателя

Prevalence of sexual dimorphism in mammalian phenotypic traits

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function