The international and legal framework for transregionalization of trade and economic cooperation of the BRICS countries

The emergence of a multipolar world is an integral part of the globalization processes. Strategic partnership at the regional, interregional and transregional levels is becoming a new institution and at the same time an instrument of modern international relations. The international and legal framework for the cooperation of BRICS as a transregional association is considered herein. The importance of converging the positions of the BRICS countries in the global political and economic system is emphasized. The research is aimed at the analysis of the international legal foundations of trade and economic cooperation of the BRICS countries within the system of transregional relations, factors, conditions and prospects for development. The measures to enhance and expand mutually beneficial trade and economic partnerships within the framework of BRICS will most effectively utilize their resource, technological, and trade and economic potential, creating the basis for the sustainable growth of the national economy and competitiveness in global development. The practical significance of the study lies in the analysis of the mechanisms of integration of BRICS. The results obtained may be useful in shaping the strategy of trade and economic cooperation within the framework of BRICS.peer-reviewe

Тяжелые респираторные осложнения как причина неблагоприятного исхода при гриппе А (H1N1sw2009) у больных с ожирением

Summary. Thirty three medical records and postmortem examination reports of patients died from influenza A virus (H1N1sw2009) in October and November, 2009, in the Transbaikal Territory were analyzed. The patients were divided into two groups. The first group consisted of 22 patients with obesity and the second group consisted of 11 patients with normal body weight. There was no difference between the groups in age, gender structure, and duration of the disease. Causes of death were pneumonia and progressive respiratory failure. The rate of acute respiratory distress syndrome was similar in both the groups. Thrombosis of various locations was seen more often in obese patients. A tendency was found to a higher rate of rhabdomyolisis, acute canalicular necrosis and intravascular coagulation blood syndrome in obese patients. Additional risk factors in those patients were diabetes mellitus, pancreatitis, and hypertension. Possible reasons of severe course of influenza A virus (H1N1sw2009) infection in obese patients, such as alveolar hypoventilation, production of proinflammatory cytokines by the fat tissue resulting in poor immune response, coagulation and metabolic disorders have been discussed in the article. All these conditions were responsible for complications and exacerbations of concomitant diseases but could not justify high mortality rate in this pandemic influenza A virus infection. The severe course of the infection may be attributable to virus A (H1N1sw2009) ability to damage the mitochondrial protein PB1-F2 and intervene into the fat exchange. Thus, obesity was the most considerable risk factor for death during influenza A virus (H1N1sw2009) outbreak in the Transbaikal Territory due to aggravation of underlying metabolic disorders by specific effects of pandemic influenza virus A strain.Резюме. Были проанализированы 33 истории болезни и протоколы вскрытий пациентов, умерших от гриппа А (H1N1sw2009) в октябре–ноябре 2009 г. в Забайкальском крае. Выделены 2 группы. Первая состояла из 22 человек, имеющих ожирение, вторая была сформирована из оставшихся 11 лиц с нормальным весом. В группах сравнения не получили разницы по возрастной и половой структуре, а также по длительности болезни. Все пациенты умерли от пневмонии и прогрессирующей дыхательной недостаточности. С одинаковой частотой развивался острый респираторный дистресс-синдром. У пациентов с избыточным весом достоверно чаще формировались тромбозы различных локализаций, имелась тенденция к более частому развитию рабдомиолиза, острого канальцевого некроза, синдрома внутрисосудистого свертывания крови. Среди дополнительных факторов риска в этой категории умерших чаще диагностировался сахарный диабет, панкреатит, артериальная гипертензия. В статье обсуждаются возможные причины тяжелого течения гриппа А (H1N1sw2009) у больных с избыточным весом: альвеолярная гиповентиляция, продукция жировой тканью провоспалительных цитокинов, ведущих к нарушению в иммунном ответе, в свертывающей системе крови, в метаболическом статусе, которые обусловили регистрируемые осложнения и сопутствующие заболевания, однако не объяснили высокую смертность именно при пандемическом гриппе. Причиной тяжелого течения инфекции, вероятно, послужила способность вируса А (H1N1sw2009) вмешиваться в жировой обмен за счет повреждения митохондрий с помощью белка PB1-F2. Таким образом, ожирение стало наиболее значимым фактором риска смерти при гриппе А (H1N1) в Забайкальском крае ввиду взаимно отягощающего влияния метаболических сдвигов, происходящих при ожирении, и особенностей пандемического штамма вируса гриппа

STUDY OF IMMUNE GENETIC RISK FACTORS OF ARTERIAL HYPERTENSION IN NATIVE AND NON-NATIVE POPULATION OF ALTAY REPUBLIC

There had been 935 people examined native to Turochaksky district of the Altai Republic (663 — indigenous people (Tubalars) and 272 — non-indigenous population) so as to identify the proportion of population with hypertension, assessment of risk factors and genetic predisposition to the disease according to the blood systems such as ABO, Rh, MN, P and Kell. The proportion of people with hypertension in the Altai Republic was 38.6 % among Tubalars and 40.8 % among non-indigenous population. The high body mass index (BMI) — (Quetelet index) values and. index: waist / hip and. waist circumference are associated, with risk of hypertension, for both ethnic groups, but only Tubalars have such risk factors as smoking and salt abuse. There had been revealed some ethnic differences in the distribution for such systems as blood group Rh factor, and MN. The indigenous ethnic group is marked with a risk of hypertension for the people with Rh(-) blood group, positive associative connection with the disease for those with the phenotype of MN and the resistance for the persons with the blood group Rh(+) and. the phenotype of NN

The NEU1-selective sialidase inhibitor, C9- butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-Nacetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to eukaryotic sialidases, C9-BA-DANA exerted far less inhibitory activity for three selected bacterial neuraminidases (IC50 \u3e 800 µM). Structural modeling of the four human sialidases and three bacterial neuraminidases revealed a loop between the seventh and eighth strands of the β-propeller fold, that in NEU1, was substantially shorter than that seen in the six other enzymes. Predicted steric hindrance between this loop and C9-BA-DANA could explain its selectivity for NEU1. Finally, pretreatment of mice with C9-BA-DANA completely protected against flagellin-induced increases in lung sialidase activity. Our combined data indicate that C9- BA-DANA inhibits endogenous and ectopically expressed sialidase activity and established NEU1-mediated bioactivities in human airway epithelia, lung microvascular endothelia, and fibroblasts in vitro and murine lungs in vivo

ИНДЕКС МАССЫ ТЕЛА И ФОРМИРОВАНИЕ СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИИ У ПАЦИЕНТОВ, ПОЛУЧАЮЩИХ ЛЕЧЕНИЕ СУПРЕССИВНЫМИ ДОЗАМИ ЛЕВОТИРОКСИНА

One of the most important problems of a long monitoring of the patients operated for thyroid carcinoma and receiving suppressive therapy with levothyroxine is the prevention of the adverse effects of treatment on the cardiovascular system. The purpose of the work is to identify the features of formation of symptoms and signs of cardiovascular diseases, as well as heart rhythm abnormalities in young patients receiving suppressive therapy with levothyroxine depending on their body mass index (BMI). Changes in the heart rate variability in patients with tachycardia and high blood pressure are studied. It is shown that patients with normal and overweight have alternative tendencies in the changes of heart rate and the formation of cardiovascular diseases.Одной из важнейших проблем длительного мониторинга пациентов, прооперированных по поводу карциномы щитовидной железы и получающих супрессивную терапию левотироксином, является профилактика побочных влияний лечения на сердечно-сосудистую систему. Цель работы – выявить особенности формирования симптомов и признаков болезней системы кровообращения, а также отклонений сердечного ритма у молодых пациентов, получающих супрессивную терапию левотироксином более 10 лет, в зависимости от их индекса массы тела. Изучены сдвиги показателей вариабельности сердечного ритма у пациентов с тахикардией и повышенным артериальным давлением. Показано, что у пациентов с нормальной и избыточной массой тела существуют альтернативные тенденции в изменениях сердечного ритма и формировании болезней системы кровообращения. Пациенты, имеющие избыточную массу тела, являются группой риска по развитию артериальной гипертензии при снижении вариабельности сердечного ритма и повышении индекса централизации, а также тонуса симпатической вегетативной нервной системы за пределы нормы. Пациенты с нормальной массой тела, имеющие повышенную вариабельность сердечного ритма, являются группой риска по развитию тахикардии и аритмии

Факторы риска микробиологической неэффективности комплексной пробиотической терапии в отношении облигатной микрофлоры кишечника больных туберкулезом с множественной лекарственной устойчивостью возбудителя

The aim of the work was to identify risk factors for the absence of a microbiological effect when using complex probiotic therapy in patients with drug-resistant tuberculosis.Material and methods. The object of the study was 30 patients with tuberculosis in the course of anti-tuberculosis therapy, who received a course of complex probiotic therapy. The patients were divided into groups according to the microbiological effect of using the probiotic against Bifido and Lactobacterium spp .: Group 1 – restoration of Lactobacterium spp. Happened, 2 – did not happen, 1A – recovery of Bifidobacterium spp. Happened, 1B did not happen. With the help of statistical processing of the material, the main risk factors for reducing its effectiveness have been identified.Research results. Among all factors (gender, social status, HIV infection, immunodeficiency, smoking, alcohol dependence, clinical form of tuberculosis and anti-tuberculosis drugs taken), the risk of reducing the efficiency of the Lactobacterium spp. in tuberculosis patients it is shown in males (OR 2.500, p = 0.029) over the age of 50 (p = 0.008). However, a significant decrease in the effectiveness of complex probiotic therapy to restore the pool of Lactobacterium spp. in the intestinal biotope is statistically significant due to the male sex (OR 8,000, p = 0.013 and the number of CD4 + lymphocytes (p = 0.005).Conclusion. The main risk factors for a decrease in the rate of recovery of the pool of Lactobacterium spp. in patients with multidrug-resistant tuberculosis, the pathogen was male and female, and the recovery of the Bifidobacterium spp. depended on the male sex and the severity of immunodeficiency in the presence of HIV infection.Целью работы являлось выявление факторов риска отсутствия микробиологического эффекта при применении комплексной пробиотической терапии у пациентов с лекарственно резистентным туберкулезом.Материалы и методы. Объектом исследования явились 30 пациентов с туберкулезом в процессе противотуберкулезной терапии, получивших курс комплексной пробиотической терапии. Пациенты были разделены на группы согласно микробиологическому эффекту применения пробиотика в отношении Bifido- и Lactobacterium spp.: 1 группа – восстановление Lactobacterium spp. произошло, 2 – не произошло, 1А – восстановление Bifidobacterium spp. произошло, 1Б – не произошло. При помощи статистической обработки материала определены основные факторы риска снижения его эффективности.Результаты. Среди всех факторов (пол, социальный статус, ВИЧ-инфекция, иммунодефицит, курение, зависимость от алкоголя, клиническая форма туберкулеза и принимаемые противотуберкулезные препарты) риск снижения эффективности восстановления пула Lactobacterium spp. у больных туберкулезом показан у лиц мужского пола (ОШ 2,500, р=0,029) в возрасте старше 50 лет (р=0,008). Однако значительное снижение эффективности комплексной пробиотической терапии на восстановление пула Lactobacterium spp. в кишечном биотопе статистически значимо обусловлено мужским полом (ОШ 8,000, р=0,013 и количеством CD4+лимфоцитов (р=0,005).Заключение. Основными факторами риска снижения скорости восстановления пула Lactobacterium spp. у больных туберкулезом с множественной лекарственной устойчивостью возбудителя явились мужской пол и возраст, а восстановление пула Bifidobacterium spp. зависело от мужского пола и выраженности иммунодефицита при наличии ВИЧ-инфекции

CD(8+ )T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

BACKGROUND: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD(8+ )TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD(3+), CD(4+ )and CD(8+)) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. METHODS: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD(68 )for macrophages, anti-elastase for neutrophils, and anti-CD(3), anti-CD(4), anti-CD(8 )for CD(3+)TLs, CD(4+)TLs, and CD(8+)TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV(1), FVC, TLC, DLCO, PaO(2), PaCO(2 )and P(A-a)O(2))] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. RESULTS: Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD(68+ )cells for the 16.6% ± 2, CD(3+ )TLs for the 28.8% ± 7, CD(4+ )TLs for the 14.5 ± 4 and CD(8+ )TLs for the 13.8 ± 4. CD(8+)TLs correlated inversely with FVC % predicted (r(s )= -0.67, p = 0.01), TLC % predicted (r(s )= -0.68, p = 0.01), DLCO % predicted (r(s )= -0.61, p = 0.04), and PaO(2 )(r(s )= -0.60, p = 0.04). Positive correlations were found between CD(8+)TLs and P(A-a)O(2 )(r(s )= 0.65, p = 0.02) and CD(8+)TLs and MRC score (r(s )= 0.63, p = 0.02). Additionally, CD(68+ )cells presented negative correlations with both FVC % predicted (r(s )= -0.80, p = 0.002) and FEV(1 )% predicted (r(s )= -0.68, p = 0.01). CONCLUSION: In UIP/IPF tissue infiltrating mononuclear cells and especially CD(8+ )TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis

WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity

In a manner dependent on CD4 T cell help and Toll-like receptor signals, B cells lacking WASp induce autoantibody production and autoimmune disease in mice

Effectiveness of mebeverine in patients with post-cholecystectomy gastrointestinal spasm: results of prospective observational program “odyssey”

Aim: to assess the effectiveness of mebeverine 200 mg BID in patients with post-cholecystectomy gastrointestinal spasm not requiring surgical treatment. Materials and methods. 218 patients were included in 16 clinical centers in 14 cities in Russia. All patients had post-cholecystectomy gastrointestinal spasms, not requiring surgical treatment and received mebeverine (Duspatalin®) 200 mg BID. The observational assessment period lasted from the moment of their inclusion into the study up to 6 weeks post inlusion. The therapy results were evaluated using visual analog scales (GPA and 11-point numeric rating scale) by patient self-assessment of the dynamics of spasm/discomfort and other post-cholecystectomic gastrointestinal symptoms after 2 and 6 weeks of treatment. Gastrointestinal Quality of Life Index (GIQLI) was used to assess patient quality of life. Results and discussion. All 218 patients completed the 2-week mebeverine treatment course, 101 of them finished the 6-week course (“prolonged population”). Significant positive changes in the relief of abdominal pain and dyspepsia were noted as well as normalization of stool frequency and consistency. A more marked change in values was observed during prolonged (up to 6 weeks) therapy. Both 2-week and 6-week mebeverine courses led to a normalization of patient quality of life. After 6 week therapy, an effect of mebeverine on the quality of life 91% of patients was observed comparable to cholecystectomy itself, speficially related to the quality of life subscore ‘symptoms’. Conclusion. The results of our study demonstrate that mebeverine (Duspatalin®) therapy leads to an effective elimination of clinical symptoms associated with post-cholecystectomy GI-spasm disorders, like abdominal pain, symptoms of dyspepsia and stooldisorders. A more marked change in values was observed during prolonged (up to 6 weeks) therapy

IL-21 Limits Peripheral Lymphocyte Numbers through T Cell Homeostatic Mechanisms

IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents.To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non-autoimmune C57BL/6 and autoimmune NOD mice. Our data indicate that IL-21R knockout C57BL/6 and NOD mice show increased size of their lymphocyte population and decreased homeostatic proliferation. In addition, our experimental results demonstrate that IL-21 inhibits T cell survival. These data suggest that IL-21 acts to limit the size of the T cell pool. Furthermore, our data suggest IL-21 may contribute to the development of autoimmunity.Taken together, our results suggest that IL-21 plays a global role in regulating T cell homeostasis, promoting the continuous adaptation of the T cell lymphoid space