Vol 70, No 2 (2015)

Article is devoted to the review of literature data, and also the analysis of results of own researches concerning genetics, molecular genetics and immunological violations at various forms of the autoimmune diabetes (DM) including classical T1DM, LADA type and an autoimmune polyglandular syndrome of 1 type (APS1). In case of T1DM more than 80% of patients are carriers of one or two strongest predisposing haplotypes: DRB1*O4-DQA1*O3O1-DQB1*O3O2 and DRB1*O3-DQA1*O5O1- DQB1*O201 designated as DQ2 and DQ8. HLA genes can model a clinical features of disease. In Russian population, the children with diabetes manifestation up to 5-year age has significantly often high risk genotypes (DQ2/DQ8) and significantly less the low risk genotypes in comparison with children, who had manifestation of T1DM in 10 years and later. The long-term
16-years family studies showed the maximum frequency of T1DM in high risk group, constantly accruing in process of increase in term of supervision, and in groups of an average and low risk lower and invariable. The highest risk of T1DM manifestation, reaching 90% at 10 years of supervision is defined by existence of HLA high risk genotypes and many antibodies, revealed from early age. LADA ― the hybrid form of autoimmune DM having signs of T1DM and T2DM in the basis. The development of autoimmune process against β-cells can be caused by only gene mutation (APS1). The part of T1DM cases which doesn't have the contributing HLA genes and autoimmune markers in process of studying of the importance of various genes and their biological value can be attributed to new, yet unknown forms of DM.

Background: At the development of graft versus host disease in genetically homogeneous population of (C57Bl/6 x DBA/2) F1 mice two clinical phenotypes of SLE-like disease were revealed: lupus+ (immune complex glomerulonephritis and hemolytic anemia) and lupus – (hemolytic anemia). The GvHD phenotypic heterogeneity is determined by the Th1 /Th2-polarization: Th2 lymphocyte predominant activity, leads to the lupus+ development, or prevalence activity of Th1 cells, leads to the lupus– development. Objective: Our aim was to evaluate the possibility of using an experimental model of autoimmune disease for studying and testing of epigenetic modifications, shifting Th1 /Th2-
balance in vivo. Methods: Сhronic GVHD was induced in B6D2F1 mice by the transplantation of 130×10 6 parental DBA/2 splenocytes. Аnti-ds-DNA, total IgG and IgG1, IgG2а Abs were measured by ELISA. Results: Six- to 8-week-old female DBA/2 and B6D2F1 mice were obtained from Biological Research Laboratory (Novosibirsk). It was established that regular moderate physical activity (unladed swimming) shifted Th1 /Th2 balance towards Th1. This leads to a decrease in a population of recipients the lupus+ mice from 57 to 26% (p <0,001) with significantly reduced hypergammaglobulinemia (IgG from 2,8 to 2,0 mg/ml; p <0,047) and DNA antibodies titer from 0,18 to 0,12 OD (p =0,05). Administration of epigenetic modificator bisphenol A at low doses, which mimicking estrogen effects, enhances the proportion of lupus+ mice in experimental groups from 33 to 64% (p <0,001) and impairs their clinical status by the increasing the urine protein level from 2.8 to 4,2 mg/ml (p <0,001) in animals. Conclusion: Th1 /Th2 – balance presumably is determined by the immune system epigenetic modification in experimental mice, formed on the previous stages of ontogeny and defines the direction of immune processes development in individual animal.

In the present paper we consider the problem of innovative treatment of systemic autoimmune diseases for example, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The use of biological therapy is suitable for severe rheumatoid arthritis and promotes remission in 25–30% of cases. Application biological therapy (as anti-B cell therapy) in cases of systemic lupus erythematosus severe forms can reduce the immuno activity level, and also leads to the regression of secondary vasculitis in lung tissue and renal parenchyma. The analysis of drugs and principles of treatment of rheumatoid arthritis and systemic lupus erythematosus was done. Particular attention is paid to the safety and efficacy of biological agents and synthetic base anti-inflammatory drugs.

This review highlights the achievements in the field of autoimmune diseases of the nervous system over the last 15 years. It became possible to deepen the understanding of medical and social significance of these diseases, form the concept of nosologic unit heterogeneity, describe new and atypical forms of demyelinating diseases of the central and peripheral nervous system, autoimmune diseases of the neuromuscular synapse. Also, it is important to mention, that the new antigens were identified, the diagnostic panel of autoantibodies was developed and put into practice. Furthermore, the clinical practice guidelines for the diagnosis and management of patients were developed, the new drugs were tested and included in these guidelines. The scientists of the biggest Russian neurological centre, Research Centre of Neurology (Moscow), developed a vaccine for immunotherapy of multiple sclerosis, studied pathomorphosis of Guillain–Barre syndrome, specified the components of its pathogenesis, improved the programs of pathogenetic therapy, which led to the decrease in mortality from 30 to 3%, helped to decrease the AVL period by 2 times, hasten the recovery of independent walking by 2.5 times. Nowadays different biomarkers of diseases of the central and peripheral nervous system are studied and modern technologies in neurorehabilitation are applied.

Bradykinin level is increased in myocardium in response to short-term ischemia/reperfusion that is one of the evidences of its trigger role in ischemic preconditioning (IP). Pharmacological induced increase of endogenous bradykinin and kallidin-like peptide levels in myocardium enhances cardiac tolerance to impact of ischemia / reperfusion. Experiments with genetically modified mice indicate that kinins are involved in preconditioning but they are not the only trigger of IP. The B₂-receptor blocking abolishes antiarrhythmic, infarct reducing effects of preconditioning, eliminates IP-induced cardiac tolerance to oxidative stress. Exogenous bradykinin mimics inotropic and cardioprotective effects of IP but does not mimic antiarrhythmic effect of preconditioning. The intracoronary or intravenous bradykinin infusion enhances human heart resistance to ischemia/reperfusion. Implementation of the cardioprotective effect of IP is provided by the activation of multiple signaling pathways that involve: B₂-receptor, calcitonin gene-related peptide, NO-synthase, guanylyl cyclase, cGMP, protein kinase G, mitochondrial K_ATP channels, reactive oxygen species, kinases C, ERK and Akt. To increase of the human heart tolerance to ischemia/reperfusion is necessary to develop B₂-receptor agonists devoid hypotensive and pro-inflammatory properties.

Objective: Our aim was to on the basis of determining the degree of violation of the structure and function of the liver establish their relationships and to assess the dynamics of liver disease in its chronic illnesses in children. Methods: With the help of the developed scoring systems were used to assess the degree of liver dysfunction and the degree of disruption of the structure of the liver and the severity of portal hypertension. Results: The results of the diagnostic methods 252 children aged 1 to 17 years (mean age of 11.8±3,5) with Wilson disease (WD), autoimmune hepatitis (AIH), chronic hepatitis C (CHC) were analyzed; 48 patients underwent liver transplantation. In children with WD, AIH and CHC liver function reduced by 41.3±12.9 % to 28.8±12.5% and 19.1±7.8% respectively. Structure of the liver in children with WD, AIH and CHC was disturbed by 25.0±8.1% to 20.4±9.2% and 6.8±4.4% respectively. The function and structure violations of the liver more pronounced in liver cirrhosis. The use of the developed scoring systems to monitor the severity of liver damage in the dynamics and evaluation of the effectiveness of the therapy is demonstrated. The degree of liver dysfunction is directly dependent on the degree of its structure. Abnormal liver function ≥40% and ≥40% of its structure with treatment failure can be used as a criterion of indications for elective liver transplantation with its chronic diseases in children. Conclusion: Developed a point system to determine liver function and a point system to determine disruption of the structure of the liver and the severity of portal hypertension in children can serve as an objective criterion for assessing the severity of liver disease, monitoring their changes in the dynamics with the assessment of the effectiveness of the therapy and making decisions about the need for routine liver transplantation in its chronic illnesses in children.

Background: Asthma is one of the urgent problems of modern pediatrics, but neuroregulation mechanisms underlying this disease have not been fully disclosed so far. The autonomic interactions assessment in patients with bronchial asthma is important to understand the pathogenesis and prognosis of the disease. Objective: The aim of the study was to investigate features of autonomic response in children with asthma in the period of exacerbation. Methods: The autonomic nervous system (ANS) of 82 children aged 6 to 18 years old with asthma in the period of exacerbation were investigated. The spectral analysis of the heart rate variability and the correlation rhythmography method (skaterography) were used to assess the ANS state. Investigations were carried out at rest and after clinoorthostatic test. Results: Non-respiratory (slow) waves reflecting the degree of activity of humoral and neural canals of heart rate central regulation were dominated at the spectrogram of 72 (87.80%) children experiencing asthma attack; more than half of patients (58.53%) had predominantly very low-frequency component (VLF%) in the range of fluctuation rate that indicated the influence of neurohumoral regulation. A significant increase in vagosympathetic balance coefficient (LF / HF) was recorded after clinoorthostatic test indicating the activation of the sympathetic nervous system. According to the correlation rhythmography data, a considerable scattering of scattergram points was detected in patients in the baseline state that indicated the predominant influence of parasympathetic nervous system. After the clinoorthostatic test, on the contrary, we observed the «tightness» of the scattergram cloud that could indicate sympathicotonia. Conclusion: The imbalance of the autonomic nervous system in the form of activation of the sympathetic and neurohumoral regulation department was found in children with asthma.

The data of foreign studies over the last 15 years devoted to endogenous synthesis and biological role of hydrogen sulfide in micromolar quantities which complemented the already two well-known gas transmitters — OH and NO are presented in this review. Despite the short period since the physiological properties of hydrogen sulfide were opened (about 20 years) it was found that this gas transmitter plays a key role in the regulation of nerve (neural signal transmission), cardiovascular (relaxation of smooth muscles), immune (anti-inflammatory and cytoprotective agent) sensory, gastrointestinal (output of insulin) systems and in the metabolism of various organs. Currently the role of H₂S in the pathogenesis of different diseases, neurodegenerative diseases, diabetes, heart failure) is being studying. The developments of drugs that act as either exogenous donors H₂S or blockers of the biosynthesis of H₂S are promising. With consideration the fact that H₂S is a representative of non-synaptic way of intercellular communication based on diffusion of molecules of inorganic compounds in the intercellular space in all directions and effect on distant from their place of formation non- synaptic receptors it is suggested to use exogenous H₂S in strict proportion for the treatment of a number of human diseases.

In this work basic stages of formation of the epidemiological surveillance of cholera in Russia are described. In 1990-s for the first time zoning by epidemic manifestations of cholera was carried out at the level of subjects forming parts of Russia and other Republics of the Soviet Union with the introduction of differential tactics of epidemiological surveillance. Improvement of epidemiological surveillance of cholera was aimed at harmonization with the IHR (2005), integration of epidemiological surveillance of cholera and social-hygienic monitoring of water objects of I and II categories. Characterization of isolated Vibrio cholerae strains (1990−2014) on the genomic basis determined the emergence of new VNTR-genotypes of V. cholerae O1 ctxAB+ tcpA+, responsible for outbreaks, simultaneously with isolation of V. cholerae O1 ctxAB^-tcpA^- strains during monitoring of environmental objects for cholera. A viewpoint is considered of the beginning of the eighth cholera pandemic in the context of emergence of V. cholerae-torstrains with CTXφ prophage carrying ctxB gene of cholera toxin of classical biovar. Main directions of further enhancement of epidemiological surveillance include the study of basic data structures used in the epidemiological surveillance system, the use of zoning of municipal units of federal subjects with corresponding surveillance tactics and expected economic effect.