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β-ЭНДОРФИН И ЦИТОКИНОВЫЙ ПРОФИЛЬ В ДИНАМИКЕ ЭКСПЕРИМЕНТАЛЬНОГО ИШЕМИЧЕСКОГО ИНСУЛЬТАТрофименко А.И., Каде А.Х., Мясникова В. В., Пирогова Н.П., Занин С.А. Федерации, Краснодар, Россия (350063, г. Краснодар, ул. Седина, 4) zanin77@mail.ru В основе развития синдрома системного воспалительного ответа при неинфекционной патологии лежит значительный рост концентрации провоспалительных цитокинов (ИЛ-1β, ИЛ-6, ФНО-α) в системной циркуляции, развивающийся при повреждении тканей. Во многом его возникновение обусловлено нарушением регуляторных механизмов контролирующих развитие воспаления, центральное место среди которых занимает эндогенная опиоидергическая система. При моделировании ишемического инсульта у крыс путем коагуляции ПСМА нарушение кровотока приводит к развитию инфаркта мозга, который локализуется преимущественно в неокортексе и захватывает небольшую область каудопутамена. На 3 сутки имеет место прирост его объема на 18,3%. Моделирование ишемического инсульта сопровождается значительным ростом содержания провоспалительных цитокинов (ИЛ-1β, ИЛ-6, ФНО-α) в периферической крови. Это явление сопровождается прогрессирующим снижением уровня β-эндорфина, что указывает на депрессию эндогенной опиоидергической стресс-лимитирующей системы при экспериментальном ишемическом инсульте. Ключевые слова: инсульт, β-эндорфин, оксидативный стресс. ГБОУ ВПО Кубанский государственный медицинский университет Министерства здравоохранения и социального развития Российской β-ENDORPHIN AND CYTOKINE PROFILE IN THE DYNAMICS OF EXPERIMENTAL IS ISCHEMIC STROKETrofimenko A.I., Kade A.H., Myasnikova V.V., Pirogova N.P., Zanin S.A. Krasnodar, Russia (350063, Krasnodar, Sedina street,4), zanin77@mail.ru At the heart of the development of systemic inflammatory response syndrome with non-infectious disease is a significant increase in the concentration of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the systemic circulation, the developing tissue injury. In many ways, his appearance due to a violation of regulatory mechanisms controlling the development of inflammation, central among which is endogenous opioidergic system. In the simulation of ischemic stroke in rats by coagulation PSMA blood flow disturbance leads to the development of cerebral infarction, which is localized mainly in the neocortex and captures a small region kaudoputamena. On day 3 there is an increase in its volume by 18.3%. Simulation ischemic stroke accompanied by significant pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the peripheral blood. This phenomenon is accompanied by a progressive decrease in the level of β-endorphins, which indicates depression of endogenous opioidergic stress-limiting system in experimental ischemic stroke. Kuban state medical university of the Ministry of Health Care of the Russian Federation,

BackgroundThe systemic scleroderma (SSc) is connective tissue disease of unknown cause. The key points in development of SSc are the increased number of high collagen-producing fibroblasts in the skin, endothelial dysfunction and immune activation. Recent studies report various metabolic disturbances in SSc patients. Purine and pyrimidine metabolic pathways are underlies the central processes of cellular life. The changes in activity of purine and pyrimidine metabolism enzymes in blood plasma and lysed lymphocytes depending on the SSc activity were described by us earlier [1]. At the same time, there are publications that confirm the relationship between changes in ADA activity in red blood cells and pronounced immune disorders [2].Objectivesto characterize enzymatic patterns of the major purine and pyrimidine metabolic pathways enzymes in lysed red blood cells depending on the SSc activity.Methods51 SSc patients and 30 healthy controls were enrolled in the study. The diagnosis was verified in accordance with the international standards (ACR/EULAR 2013). Disease activity was assessed in accordance with the national classification [3]. Adenosine deaminase (ADA; EC 3.5.4.4); adenosine kinase (AK; EC 2.7.1.20); guanylate kinase (GK; EC 2.7.4.8), dihydroorotate dehydrogenase (DODH; DC 1.3.1.14); IMP dehydrogenase (IMPDH; EC 1.1.1.205); purine nucleoside phosphorylase (PNP; EC 2.4.2.1); thymidine kinase (TK; EC 2.7.1.21); thymidine phosphorylase (TP; EC 2.4.2.4); uracil/thymidine dehydrogenase (UDH; EC 1.17.99.4); cytidine deaminase (CDA; EC 3.5.4.5) activities were measured in lysed red blood cells.ResultsMean age of patients (Mean± SD) was 42.8±1.3years, mean SSc duration was 7.9±0.7 years. We revealed substantial changes in enzymatic activities related to both purine and pyrimidine metabolism in lysed red blood cells of SSc patients. The increased ADA (p<0,001), AK (p<0,001), IMPDH (p<0,001), TK (p<0,001), UDH (p<0,001) activities and the decreased DODH (p<0,001), PNP (p<0,001) activities in lysed red blood cells were observed of SSc patients in comparison with healthy controls. AK, IMPDH, TK, UDH activities positively correlated with SSc activity. Negative correlations with SSc activity were revealed for ADA, CDA, DODG, GK, PNP, TP activities.ConclusionThe progression of SSc goes with the imbalance of the purine and pyrimidine enzymes in a regular manner. Activity of the autoimmune inflammation is the factor that underlies the enzymatic pattern of purine and pyrimidine metabolism.References[1] Mozgovaya E., Bedina S., Trofimenko A., Zborovskaya I. The association between activity of purine and pyrimidine metabolism enzymes and disease activity in systemic scleroderma patients. Annals of the Rheumatic Diseases2018;77(2):1280.[2] Cowan M.J., Brady R.O., Widder K.J. Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1986Feb;83(4):108.[3] Guseva N.G. Systemic scleroderma. M.: Medicine,1993.268 p.Disclosure of InterestsNone declared

Background:The oxidative-related enzymes are involved in the pathogenesis of various stages of systemic sclerosis (SSc). SSc is a chronic autoimmune disorder that is intimately associated with vascular damage and therefore with chronic perfusion/reperfusion and oxidative organ injury. Mesenchymal cell activation in SSc is now also considered to be mediated primarily through oxidative burst. Regulation of oxidative stress by specific enzymes including several purine metabolism enzymes is likely to play an important role in SSc progression.Objectives:to characterize interrelationships among circulating xanthine oxidase (XO), xanthine dehydrogenase (XDH), superoxide dismutase (SOD) activities and SSc activity.Methods:The study was performed according to bioethical standards. 51 patients with verified SSc and 30 healthy controls were included in the study. The diagnosis was verified according to ACR/EULAR 2013 criteria. We assessed SSc activity in compliance with the original activity scale that is commonly used in Russia [Guseva N.G., 1993] and by the 2001 European Scleroderma Study Group Activity Index. XO (EC 1.17.3.2), XDH (EC 1.17.1.4), and SOD (EC 1.15.1.1) plasma activities were measured using spectrophotometric techniques as previously described [Dubinina E.E., 1986; Karpova O.V., 2006]. Results are expressed as mean±SD. The Mann-Whitney U test and Spearman’s correlation coefficient were used for statistical analysis.Results:Mean age of patients was 42.8±1.3 years, mean SSc duration was 7.9±0.7 years. Mean enzymatic activities in normal controls were 3.43±0.56 nmol/ml min (for XO), 5.19±0.71 nmol/ml min (for XDH), and 5.40±1.03 units (for SOD). The respective enzymatic activities in SSc group were 3.91±0.62 nmol/ml min, 7.10±0.71 nmol/ml min, and 7.10±2.19 units. All these mean activities were significantly higher in SSc patients comparing to healthy individuals (p<0.001). XO and XDH activities positively correlated with SSc activity (r=0.499, p<0.001, and r=0.741, p<0.001, respectively). The opposite but weaker trend was observed for SOD activity and SSc disease activity (r=-0.190, p=0.188).Conclusion:SSc is characterized by an increase in the intensity of oxidative and antioxidant processes, more pronounced in high disease activity. A close relationship between function of prooxidant/antioxidant enzymes and some of the key SSc pathogenetic mechanisms, especially vascular disease and fibroblast activation, is widely considered. Overall increase of oxidative stress in patients with higher disease activity, as well as depletion of antioxidant capacity can be also linked with disturbance of purine metabolism through XO and XDH modulation. Pathogenetic influence of this imbalance can also be mediated through initial phase of neutrophil extracellular traps (NETs) formation, an eventual source of nucleoprotein containing autoepitopes.Disclosure of Interests:None declared