CLINICAL AND IMMUNOLOGICAL FEATURES OF KIDNEY TRANSPLANT RECIPIENTS WITH CYTOMEGALOVIRUS INFECTION MANIFESTATION IN THE EARLY POSTOPERATIVE PERIOD

Aim. To optimize the management of postoperative renal allograft recipients through the introduction of methods for predicting risk of manifestation of cytomegalovirus infection on the basis of a comprehensive assessment of the clinical and immunological status. Materials and methods. We retrospectively analyzed the medical records of 303 patients with end-stage renal disease, among them – were the recipients of renal allograft – 136, among whom 29 within 2 months after the operation had clinical signs of CMV infection. Assessable "CMV syndrome", laboratory evidence of CMV infection, the incidence of antigens (genes) of HLA A, B and DRB *1, calculated goodness of fit χ2 and relative risk RR, changes MCP-1 in urine. Results. In renal allograft recipients with clinical and laboratory evidence of CMV infection in the early postoperative period, significantly more (χ2 > 3,8) met antigen B35. A positive association with CMV infection was detected also for DRB1 * 08, B21, B22, B41, A24 (9), B51 (5), DRB1*14 and DRB1*15. Protective effects possessed antigens / alleles of genes A26 (10), B14, B38 (16) B61 (40) and DRB1*16. MCP-1 levels in this group of recipients were raised to 2174,7 ± 296,3 pg/ml with a strong negative correlation with the levels of urea and creatinine in serum (r = 0,9, p < 0.001). Conclusion. Immunological markers of risk manifestation of CMV infection in recipients of kidneys in the early postoperative period are: the carriage of В35 и В55,56(22), В49(21), В41, DRB1*08 и DRB1*15, an increase of levels of MCP-1 in urine without increasing the levels of urea and creatinine in the serum

Comparative evaluation of immune parameters under different pathologic conditions

Immune cell subpopulations were studied with the help of flow cytometry technique under different pathologic conditions: chronic infectious inflammation and aseptic acute inflammation. Dispersion of immune parameters has increased in both cases (in comparison to the control group with normal individuals). Immune cells percentage has changed without common trend, but their absolute count has decreased in both examined groups. Received results are in agreement to concept of stereotypical immune response to different antigens.С помощью методов лазерной проточной цитофлюориметрии изучена направленность изменений в составе иммунокомпетентных клеток крови при патологических состояниях, возникающих при хроническом инфекционном воспалении и остром асептическом воспалении. Показано, что при изучаемых процессах увеличивается вариабельность иммунологических показателей по сравнению со здоровыми донорами; относительное содержание иммунокомпетентных клеток в крови меняется разнонаправлено, в то же время абсолютное их число снижается в обеих группах. Полученные результаты соответствуют концепции стереотипного реагирования иммунной системы на экзогенный и эндогенный антиген

Omega-3 Polyunsaturated Fatty Acids: the Role in Prevention of Atrial Fibrillation in Patients with Coronary Artery Disease after Coronary Artery Bypass Graft Surgery

Aim. To estimate the role of omega-3 polyunsaturated fatty acids (PUFAs) administration in atrial fibrillation (AF) prevention after planned coronary artery bypass graft (CABG) surgery.Material and Methods. Studied were 306 patients divided into two groups: patients of group I didn’t receive PUFAs (158 patients, 82.7% males) and patients of group II received PUFAs (148 patients, 89.3% males). PUFAs were prescribed in daily dose 2000 mg 5 days before surgery and in daily dose 1000 mg in postoperative period during 21 days.Results. Postoperative AF (POAF) occurred in 29.7% patients in group I and in 16.9% patients in group II (р=0.009). We found that after CABG in patients of the I group median IL-6 level was 39.3% higher (p=0.001), interleukin-10 – 20.2% higher (p=0.01), superoxide dismutase – 78.9% higher (р<0.001), malondialdehyde – 33.8% higher (p=0.03), docosahexaenoic acid – 31.8% lower (p=0.01) and omega-3 index – 43.4%    lower (p=0.04) than in patients of the II group.According to multivariate regression analysis we found significant association between the factors of inflammation, oxidative stress and the risk POAF development.Conclusions. In patients who took PUFAs, we found less activation of inflammation, oxidative stress, the increasing of docosahexaenoic acid and omega-3 index accompanied by the decreasing of POAF development rates up to 12.8%

Experimental models of pulmonary embolism

Pulmonary embolism (PE) ranks third in the structure of acute cardiovascular diseases. Every year there is a rapid increase in morbidity and mortality from PE. Laboratory biomarkers for PE diagnosis do not have the necessary specificity, and therefore are ineffective. PE requires timely active treatment, in particular for the prevention of serious complications. In this regard, further research is needed to study and search for novel promising biomarkers for the early detection of PE, pathophysiological mechanisms and targets for therapeutic effects. To a large extent, novel data on the pathophysiology of cardiovascular diseases, including PE, scientists receive from experimental studies using animal models. In this review, we summarize the main existing experimental models of PE, describe the principles and methods for modeling this disease. There are following models of PE: intravenous thrombin infusion, adenosine diphosphate-induced PE, PE induction by thromboplastin, recombinant human tissue factor or high molecular weight polyphosphates, collagen/adrenaline-induced PE, ex vivo thrombus intravenous administration, surgical model. This publication also presents our own experience in creating an artificial model of PE in animals using an intravenous thrombus. In our model, confirmation of PE was obtained during pathological examination and an increase in the level of following biomarkers: troponin, N-terminal pro-brain natriuretic peptide, and D-dimer. In this pilot study, a PE model was created to study the pathogenesis and novel treatment options for this disease. To confirm the effectiveness of the model, future studies are required

Дефицит витамина D как фактор риска неконтролируемого течения бронхиальной астмы

The aim of this study was to determine a relationship between IL-17, IL-10 and vitamin D concentrations and asthma control level in adult patients.Methods. This was a comparative study which involved 79 asthma patients. The patients were divided in two groups: 48 patients with good control of asthma (mean age, 52 ± 13 years; BMI, 24.9 (21.6 – 28.3) kg/m2) and 31 patients with uncontrolled asthma (mean age, 57.6 ± 7.9 years; BMI, 29.1 (27.3 – 33.6) kg/m2). Concentrations of IL-10, IL-17 and vitamin D were measured in blood serum using ELISA assay.Results. Vitamin D concentration was significantly lower in patients with uncontrolled asthma compared to well-controlled asthma. An inverse relationship was found between vitamin D and IL-17 blood concentrations but not between vitamin D and IL-10 blood concentrations.Conclusion. Serum concentration of vitamin D could be used as a predictor of asthma course and control.Несмотря на значительные достижения современной медицины в профилактике и лечении бронхиальной астмы (БА), до сих пор отмечается значительное число случаев неконтролируемого или частично контролируемого течения заболевания. При этом у больных снижается работоспособность, нарушается качество сна из-за ночных приступов удушья, снижается качество жизни. Целью исследования явилось определение взаимосвязи уровня витамина D, интерлейкинов (IL)-17 и -10 со степенью контроля над БА у взрослых.Материалы и методы. В исследовании приняли участие пациенты (n = 79), страдающие БА. Выделены 2 группы: 1-я (n = 48; возраст – 52 ± 13 лет; индекс массы тела (ИМТ) – 24,9 (21,6–28,3) кг / м2) – лица с контролируемой БА; 2-я (n = 31; возраст – 57,6 ± 7,9 года; ИМТ – 29,1 (27,3–33,6) кг / м2) – с неконтролируемой БА. При помощи метода иммуноферментного анализа изучено содержание витамина D, IL-17 и IL-10 в сыворотке крови. Результаты. По результатам исследования у пациентов с неконтролируемой БА выявлен более низкий уровень витамина D в сравнении с лицами группы контролируемой БА (p < 0,05). Также установлена обратная корреляционная связь между уровнем витамина D и уровнем IL-17 в сыворотке крови у больных БА (p < 0,05). Достоверной корреляции между уровнем витамина D и уровнем IL-10 не отмечено. Заключение. Установлено, что уровень витамина D можно рассматривать как прогностический фактор, определяющий течение БА и уровень контроля над указанным заболеванием, а при сопоставлении уровня витамина D и IL-17 подтверждена противовоспалительная роль витамина D при БА

Молекулярно-генетические маркеры риска развития кардиотоксичности, индуцированной химиотерапией, у больных онкогематологическими заболеваниями: обзор литературы

Cardiotoxicity of anticancer therapy is a severe adverse cardiovascular event affecting the survival of cancer patients. Modern methods for diagnosing cardiotoxicity allow to identify already occurred myocardial transformations, accompanied by symptoms of heart failure and are not predict and detect early changes in the heart tissue during treatment. Recently, increasing attention is paid to the search for molecular genetic markers, a single identification of which before starting treatment will make possible to determining the risks of cardiotoxicity and change treatment taking into account individual genetic characteristics. At the same time, most research on the effect of allelic variants of genes on cardio-vascular complications relate to chemotherapy of solid tumors. The review considered possible prognostic genetic variants of cardiotoxicity induced by chemotherapy in patients with the hematopoietic and lymphatic malignancies.Кардиотоксичность противоопухолевых препаратов является серьезным нежелательным явлением со стороны сердечно-сосудистой  системы, неблагоприятно  влияющим на выживаемость онкологических больных. Современные методы диагностики кардиотоксических эффектов основаны на выявлении уже существующих повреждений,  сопряженных с симптомами сердечной недостаточности, и не подходят для прогнозирования ранних изменений в сердечной ткани на фоне лечения. В последнее время все больше внимания уделяется поиску молекулярно-генетических маркеров, однократная идентификация которых до начала лечения позволит определить риск развития кардиотоксичности и скорректировать терапию с учетом индивидуальных генетических особенностей пациентов. при этом большинство исследований влияния аллельных вариантов генов на сердечно-сосудистые осложнения относятся к химиотерапии солидных опухолей. В данном  обзоре рассмотрены возможные прогностические генетические варианты риска развития кардиотоксичности, индуцированной химиотерапией, у пациентов со злокачественными новообразованиями  лимфатической и кроветворной тканей

КЛИНИКО-ИММУНОЛОГИЧЕСКИЕ ОСОБЕННОСТИ РЕЦИПИЕНТОВ АЛЛОТРАНСПЛАНТАТА ПОЧКИ С МАНИФЕСТАЦИЕЙ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ В РАННЕМ ПОСТОПЕРАЦИОННОМ ПЕРИОДЕ

Aim. To optimize the management of postoperative renal allograft recipients through the introduction of methods for predicting risk of manifestation of cytomegalovirus infection on the basis of a comprehensive assessment of the clinical and immunological status. Materials and methods. We retrospectively analyzed the medical records of 303 patients with end-stage renal disease, among them – were the recipients of renal allograft – 136, among whom 29 within 2 months after the operation had clinical signs of CMV infection. Assessable "CMV syndrome", laboratory evidence of CMV infection, the incidence of antigens (genes) of HLA A, B and DRB *1, calculated goodness of fit χ2 and relative risk RR, changes MCP-1 in urine. Results. In renal allograft recipients with clinical and laboratory evidence of CMV infection in the early postoperative period, significantly more (χ2 > 3,8) met antigen B35. A positive association with CMV infection was detected also for DRB1 * 08, B21, B22, B41, A24 (9), B51 (5), DRB1*14 and DRB1*15. Protective effects possessed antigens / alleles of genes A26 (10), B14, B38 (16) B61 (40) and DRB1*16. MCP-1 levels in this group of recipients were raised to 2174,7 ± 296,3 pg/ml with a strong negative correlation with the levels of urea and creatinine in serum (r = 0,9, p < 0.001). Conclusion. Immunological markers of risk manifestation of CMV infection in recipients of kidneys in the early postoperative period are: the carriage of В35 и В55,56(22), В49(21), В41, DRB1*08 и DRB1*15, an increase of levels of MCP-1 in urine without increasing the levels of urea and creatinine in the serum. Цель: оптимизировать постоперационное ведение реципиентов почечного аллотрансплантата за счет прогнозирования рисков манифестации цитомегаловирусной инфекции на основании комплексной оценки клинико-иммунологического статуса. Материалы и методы. Ретроспективно были проанализирова- ны истории болезни 303 пациентов с терминальной стадией хронической почечной недостаточности, из них 136 являлись реципиентами аллопочки, среди которых у 29 в течение двух месяцев после операции имели место клинические признаки ЦМВ-инфекции. Оценивали проявления ЦМВ-синдрома, наличие лабораторных признаков ЦМВ-инфекции, частоту встречаемости антигенов (генов) системы HLA локусов А, В и DRB*1 с расчетом критерия согласия χ2 и относительного риска RR, изменение уровня МСР-1 в моче. Результаты. У реципиентов аллотрансплантата почки с клиническими и лабораторными признаками ЦМВ-инфекции в раннем постоперационном периоде статистически значимо чаще (χ2 > 3,8) встречался антиген В35. Положительная ассоциация с ЦМВ-инфекцией была выявлена также для DRB1*08, В21, В22, В41, А24(9), В51(5), DRB1*14 и DRB1*15. Протективными свойствами обладали антигены / аллели генов А26(10), В14, В38(16), В61(40) и DRB1*16. У данной группы реципиентов уровни МСР-1 поднимались до 2174,7 ± 296,3 пг/мл при сильной отрицательной корреляции с уровнями мочевины и креатинина в сыворотке крови (r = 0,9, р < 0,001).Заключение. Иммунологическими маркерами высокого риска манифестации ЦМВ-инфекции у реципиентов почки в раннем постоперационном периоде явля- ются: носительство В35 и В55,56(22), В49(21), В41, DRB1*08 и DRB1*15 и увеличение уровней МСР-1 в моче без увеличения уровней мочевины и креатинина в сыворотке крови.

Эффективность и безопасность эрибулина при различных подтипах рака молочной железы: данные из реальной клинической практики в России

The article presents a pooled experience of the use of eribulin in the real clinical practice of treatment of metastatic breast cancer in Russian oncological institutions. The effectiveness of the drug in monotherapy with HER2‑negative breast cancer was analyzed, groups of patients with most effective use of eribulin were identified depending on the localization of metastases, the most effective lines of therapy. The effectiveness of the drug in combination with trastuzumab in HER2‑positive breast cancer is described, as well as toxic reactions. В статье представлен обобщенный опыт применения эрибулина в реальной клинической практике онкологических учреждений РФ при метастатическом раке молочной железы. Проанализирована эффективность препарата в монотерапии при HER2-отрицательном раке молочных желез, выделены группы больных в зависимости от локализации метастазов, линии терапии, в которых препарат оказался максимально эффективным. Описана эффективность препарата в комбинации с трастузумабом при HER2-положительном раке молочной железы, а также токсические реакции. 

Dynamical downscaling of historical climate over CORDEX Central America domain with a regionally coupled atmosphere–ocean model

The climate in Mexico and Central America is influenced by the Pacific and the Atlantic oceanic basins and atmospheric conditions over continental North and South America. These factors and important ocean–atmosphere coupled processes make the region’s climate a great challenge for global and regional climate modeling. We explore the benefits that coupled regional climate models may introduce in the representation of the regional climate with a set of coupled and uncoupled simulations forced by reanalysis and global model data. Uncoupled simulations tend to stay close to the large-scale patterns of the driving fields, particularly over the ocean, while over land they are modified by the regional atmospheric model physics and the improved orography representation. The regional coupled model adds to the reanalysis forcing the air–sea interaction, which is also better resolved than in the global model. Simulated fields are modified over the ocean, improving the representation of the key regional structures such as the Intertropical Convergence Zone and the Caribbean Low Level Jet. Higher resolution leads to improvements over land and in regions of intense air–sea interaction, e.g., off the coast of California. The coupled downscaling improves the representation of the Mid Summer Drought and the meridional rainfall distribution in southernmost Central America. Over the regions of humid climate, the coupling corrects the wet bias of the uncoupled runs and alleviates the dry bias of the driving model, yielding a rainfall seasonal cycle similar to that in the reanalysis-driven experiments.Universidad de Costa Rca/[805-B7-507]/UCR/Costa RicaCRYOPERU/[144-2015]//PerúUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Prognostic value of neutrophil gelatinase-associated lipocalin and cystatin C in patients with heart failure and previous myocardial infarction

Aim. To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2) and cystatin C in patients with heart failure (HF) and myocardial infarction (MI).Material and methods. Baseline plasma concentrations of NGAL and cystatin C were measured in 119 participants (median age, 50-61 years; men, 101) with HF and primary MI (4-6 weeks old) who underwent percutaneous coronary intervention in the acute period. Adverse cardiovascular events within 1 year were considered as the endpoint.Results. Patients with elevated NGAL levels were significantly more likely to have adverse events (p<0,001). The optimal cut-off value for NGAL was 18,75 ng/ml (odds ratio, 10, 95% CI, 3,09-32,45; p=0,0001). Multivariate logistic regression showed that NGAL, N-terminal pro-brain natriuretic peptide, left ventricular aneurysm, and SYNTAX score were significant predictors of adverse events. Cystatin C did not affect prognosis in the study cohort.Conclusion. Increased NGAL levels is a predictor of unfavorable clinical outcome in patients with HF and previous MI