DYNAMICALLY DETERMINE TOLL-RECEPTORS PATIENTS WITH ULCERATIVE COLITIS

Purpose: Dynamic determination of TLR 2,4,6 in patients with relapsed UC with an assessment of the use of indicators characterizing the state of TLR, as markers of remission.Materials and Methods: The study included 86 patients with recurrent UC, 39 of which have reached clinical and endoscopic remission. TLR expression on peripheral blood monocytes was determined in immunofluorescence test using monoclonal antibodies to TLR2 (СD14+CD282+), TLR4 (СD14+CD284+) и TLR6 (СD14+CD286+), conjugated with FITC (fluorescein isothiocyanate) and PE (phycoerythrin) - labeled (HyCultbiotechnology, Holland).Results: number of monocytes expressing TLR 2,4,6 increased activation of the inflammatory process, with remission rates expression of TLR 2,4,6 not different from those in the control group.Conclusion: you can use the number of monocytes expressing TLR 2,4,6 as a marker of remission

RISK ASSESSMENT MODEL FOR CORONARY ATHEROSCLEROSIS IN PATIENTS WITH VISCERAL OBESITY

Aim. To invent a model for coronary atherosclerosis risk prediction in patients with visceral obesity and to conduct comparison research for this model with the other known Framingham and PROCAM.Material and methods. Totally 67 men included, of the age 40-65 (50,95±6,54 y.o.) without angina pectoris and clinical signs of another localization atherosclerosis. Patients had general obesity of I-III grade with BMI 35,16±3,32 kg/m , and visceral obesity by the thickness of epicaridal fat >7 mm. After coronary arteriography or multidetector computed tomography of coronary arteries we selected 2 comparison groups: group I (n=25) — patients with coronary atherosclerosis, group II (n=42) — without. For the invention of the prognostic score we used regression model with regression and optimal scaling.Results. Potential predictors of coronary atherosclerosis riskas a result of two groups comparison were: arterial hypertension, carbohydrate metabolism disorders, triglycerides, leptin, adiponectin and C-rective protein. As the result of regression analysis each predictor got its own significance mark. The rate of correctclassifications reached 79,1% that shows good prognostic value of this regression model. While using Framingham and PROCAM model the prognostic value of subclinical coronary atherosclerosis was 24,6% and 21,6% lower, resp., than the new risk assessment. Conclusion. The model invented of the risk assessment in visceral obesity patients makes it possible to take into account the main pathogenetic mechanisms that connect obesity and coronary atherosclerosis

Сывороточные биомаркеры сердечной недостаточности и параметры механики левого желудочка в ранней диагностике диастолической дисфункции у пациентов с эпикардиальным ожирением

Highlights. Patients with epicardial obesity develop myocardial fibrosis (the underlying mechanism of left ventricular diastolic dysfunction) the preclinical diagnosis of which is difficult to perform. In this regard, the search for non-invasive methods for diagnosing diastolic dysfunction at an early stage, including the methods of determining the serum level of biomarkers of heart failure and studying the parameters of left ventricular mechanics using speckle-tracking echocardiography, seems quite relevant.Background. Currently, the search for serum biomarkers and non-invasive methods for diagnosing diastolic dysfunction (DD) of the left ventricle (LV) at the preclinical stage in obese patients is relevant.Aim. To study the levels of heart failure biomarkers and their association with profibrotic factors and LV mechanics in patients depending on the presence of epicardial obesity (EO).Methods. Out of 143 men with general obesity, depending on the severity of EO, determined by the thickness of epicardial adipose tissue (tEАT), 2 groups of patients were identified: the EO (+) group with tEАT 7 mm or more (n = 70), and the EO (–) group with tEАT less than 7 mm (n = 40). The exclusion criteria from the study were: arterial hypertension, type 2 diabetes mellitus, coronary artery disease, and the presence of LVDD detected by echocardiography (echo). Levels of profibrotic factors (type I and type III collagen, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase-3 (MMP-3), transforming growth factor-β (TGF-β), vascular endothelial growth factor A (VEGF-A), sST2, and NT-proBNP were determined in all patients using enzyme immunoassay. With the help of speckle-tracking echocardiography, the mechanics of LV were analyzed.Results. The EO (+) group presented with increased sST2 level (22.11±7.36 ng/mL) compared to the EO (–) group (sST2 level 9.79±3.14 ng/mL (p<0.0001). In the EO (+) group, a significant influence of tEAT on sST2 level was identified (F = 8.57; p = 0.005). In the EO (+) group, an increase in the level of MMP-3, type I collagen, type III collagen, PICP, transforming growth factor-β, and VEGF-A was revealed. Moreover, in the EO (+) group, a statistically significant relationship between sST2 and type III collagen was revealed (p = 0.01). When comparing the parameters of speckle-tracking echo, the EO group (+) presented with increased LV untwisting rate of –128.31 (–142.0; –118.0) deg/s-1 (p = 0.002), and increased time to LV peak untwisting rate of – 476.44 (510.0; 411.0) msec compared with the EO group (–) (p = 0.03). Moreover, a significant association between LV untwisting rate and sST2 level was revealed in the EO (+) group (r = 0.35; p = 0.02).>˂0.0001). In the EO (+) group, a significant influence of tEAT on sST2 level was identified (F = 8.57; p = 0.005). In the EO (+) group, an increase in the level of MMP-3, type I collagen, type III collagen, PICP, transforming growth factor-β, and VEGF-A was revealed. Moreover, in the EO (+) group, a statistically significant relationship between sST2 and type III collagen was revealed (p = 0.01). When comparing the parameters of speckle-tracking echo, the EO group (+) presented with increased LV untwisting rate of –128.31 (–142.0; –118.0) deg/s-1 (p = 0.002), and increased time to LV peak untwisting rate of – 476.44 (510.0; 411.0) msec compared with the EO group (–) (p = 0.03). Moreover, a significant association between LV untwisting rate and sST2 level was revealed in the EO (+) group (r = 0.35; p = 0.02).Conclusion. The data obtained indicate that patients with EO have LVDD, which could not be detected using echo criteria for LVDD, and the determination of serum levels of the heart failure biomarker - sST2 can be used for the diagnosis of LVDD at the early stage.Основные положения. У пациентов с эпикардиальным ожирением развивается фиброз миокарда, лежащий в основе нарушения диастолической функции левого желудочка, доклиническая диагностика которого затруднительна. В связи с этим крайне актуален поиск неинвазивных методов диагностики диастолической дисфункции на ранней стадии, в том числе с помощью определения сывороточного уровня биомаркеров сердечной недостаточности и изучения параметров механики левого желудочка с применением speckle-tracking эхокардиографии.Актуальность. В настоящее время актуален поиск неинвазивных методов диагностики диастолической дисфункции (ДД) левого желудочка (ЛЖ) на доклиническом этапе, в том числе у пациентов с ожирением.Цель. Изучить уровни биомаркеров сердечной недостаточности и их ассоциацию с профибротическими факторами и параметрами механики ЛЖ у пациентов в зависимости от наличия эпикардиального ожирения (ЭО).Материалы и методы. Из 143 мужчин с общим ожирением в зависимости от степени выраженности ЭО, определенного по толщине эпикардиальной жировой ткани (тЭЖТ), выделены две группы: ЭО(+) – тЭЖТ 7 и более мм (n = 70), ЭО(–) – тЭЖТ менее 7 мм (n = 40). Критерии исключения из исследования: артериальная гипертензия, сахарный диабет 2-го типа, ишемическая болезнь сердца, а также наличие ДД ЛЖ, выявленной по данным эхокардиографии (ЭхоКГ). Всем пациентам определяли уровень профибротических факторов (коллаген I и III типов, проколлаген I C-концевого пропептида (PICP), матриксная металлопротеиназа-3 (MMП-3), трансформирующий фактор роста-β (TGF-β), сосудистый эндотелиальный фактор рост (VEGFA)), sST2 и NT-proBNP исследовали с использованием иммуноферментного анализа. С помощью speckle-tracking ЭхоКГ изучена механика ЛЖ.Результаты. В группе ЭО(+) выявлено повышение уровня sST2 до 22,11±7,36 нг/мл в сравнении с группой ЭО(–), где уровень sST2 составил 9,79±3,14 нг/мл (р<0,0001). В группе ЭО(+) определено значимое влияние тЭЖТ на уровень sST2 (F = 8,57; p = 0,005). Также в группе ЭО(+) зарегистрировано увеличение уровня ММП-3, коллагена I и III типов, PICP, TGF-β, VEGFA; определена статистически значимая взаимосвязь sST2 и коллагена III типа (p = 0,01). При сравнении показателей speckle-tracking ЭхоКГ в группе ЭО(+) в сравнении с группой ЭО(–) отмечено повышение скорости раскручивания ЛЖ до –128,31 (–142,0; –118,0) градуса/с–1 (p = 0,002) и времени до пика раскручивания ЛЖ до 476,44 (510,0; 411,0) мсек (p = 0,03). В данной группе выявлена взаимосвязь скорости раскручивания ЛЖ и уровня sST2 (r = 0,35; p = 0,02). >˂0,0001). В группе ЭО(+) определено значимое влияние тЭЖТ на уровень sST2 (F = 8,57; p = 0,005). Также в группе ЭО(+) зарегистрировано увеличение уровня ММП-3, коллагена I и III типов, PICP, TGF-β, VEGFA; определена статистически значимая взаимосвязь sST2 и коллагена III типа (p = 0,01). При сравнении показателей speckle-tracking ЭхоКГ в группе ЭО(+) в сравнении с группой ЭО(–) отмечено повышение скорости раскручивания ЛЖ до –128,31 (–142,0; –118,0) градуса/с–1 (p = 0,002) и времени до пика раскручивания ЛЖ до 476,44 (510,0; 411,0) мсек (p = 0,03). В данной группе выявлена взаимосвязь скорости раскручивания ЛЖ и уровня sST2 (r = 0,35; p = 0,02).Заключение. Полученные данные позволяют предположить, что у пациентов с ЭО может быть ДД ЛЖ, не выявленная с помощью ЭхоКГ-критериев нарушения диастолической функции ЛЖ, а определение уровня сывороточного биомаркера сердечной недостаточности sST2 возможно для диагностики ДД на ранней стадии

Organizational-administrative Features of the Implementation of Educational Services in the Two-level System of Training of Highly Qualified Personnel

It is education - the system of formation of the nation's intellectual capital and as one of the main areas of production innovation - creating the basic conditions for intensive growth of the markets on the basis of rapid updating of technologies and products. Education acts as the first link "education - research - innovation development of mass" of the innovation cycle. This educational sphere acts not only as a necessary element of reproduction of intellectual capital, but also as a dominant element of economic growth, which determines the stability of the external and internal competitive advantages of national economic systems. From the power of the national economy play an individual and a public intellectual capital, which implements the level of economic thinking of the nation, it is largely determined by economic strength, well-being, and the choice of its strategy and the subsequent trajectory of development in a global world order. In this connection, the Russian education there are urgent tasks related to the need to comply with the transformation of the education sector changes. Keywords: economic growth, educational service, training, educational organization JEL Classifications: G20, L00, O4

Expression of CD80 and HLA-DR molecules on blood monocytes in patients with pulmonary tuberculosis

We examined expression pattern of CD80 and HLA-DR pro-inflammatory molecules on the monocytes in patients with pulmonary tuberculosis (TB), depending on the clinical form of the disease and susceptibility of the pathogen to anti-tuberculosis drugs. The study involved forty-five patients with newly diagnosed pulmonary TB (25 men and 20 women aged 18 to 55 years, average age — 44.0±12.4 years). The control group included 15 healthy donors with similar socio-demographic characteristics as in TB patients. Venous blood was used as biomaterial for assays. Studies of the monocyte immunophenotype were carried out by flow cytometry of whole blood cells using Cytoflex flow cytometer (Beckman Coulter, USA) with specific monoclonal antibodies (eBioscience, USA). We determined the content of cells expressing surface markers of monocytes, i.e., CD14, CD45, CD80, and HLA-DR. The results of this study were evaluated using SPSS Statistics 17.0 standard software package and Microsoft Excel. In the course of the study, we have suggested a working hypothesis that the monocytes in TB patients, still being in circulation, can express activation markers during their migration to inflammation focus, especially CD80 and HLA-DR molecules. Analysis of the total CD14+ monocyte number showed its decrease in all forms and variants of clinical course of pulmonary tuberculosis compared with the control group. Assessment of pro-inflammatory markers expressed on CD14 positive monocytes, i.e., HLA-DR activation marker and CD80 co-stimulatory molecule, showed that the number of monocytes with HLA-DR expression in all TB patients was higher than in healthy donors. HLA- DR expression on CD14+ monocytes in the group of patients with infiltrative TB proved to be 15% higher than in patients with disseminated TB. The expression of CD80 on CD14+ monocytes in TB patients showed no differences between the groups and varied within the normal range. Hence, an imbalance within monocyte population in patients with pulmonary tuberculosis, regardless of its clinical form and drug sensitivity of the pathogen is developed, due to decrease in total number of CD14+ cells, along with increased relative number of monocytes expressing HLA-DR activation marker (pro-inflammatory phenotype). Meanwhile, expression of the CD80 co-stimulatory molecule on monocytes was within normal values

Дифференциация и субпопуляционный состав VEGFR2+ моноцитов крови и костного мозга при ишемической кардиомиопатии

Aim. To identify disturbances of differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow associated with the features of the cytokine profile in the blood and bone marrow in patients with coronary artery disease (CAD) with and without ischemic cardiomyopathy (ICM).Materials and methods. The study included 74 patients with СAD with and without ICM (30 and 44 people, respectively) and 18 healthy donors. In all patients with СAD, peripheral blood sampling was performed immediately before coronary artery bypass grafting, and bone marrow samples were taken during the surgery via a sternal incision. In the healthy donors, only peripheral blood sampling was performed. In the bone marrow and blood samples, the number of VEGFR2+ cells (CD14+VEGFR2+ cells) and their immunophenotypes CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was determined by flow cytometry. Using enzyme-linked immunosorbent assay, the levels of VЕGF-А, TNFα, M-CSF, and IL-13, as well as the content of MCP-1 (only in the blood) and the M-CSF / IL-13 ratio (only in the bone marrow) were determined.Results. The content of CD14+VEGFR2+ cells in the blood of CAD patients with and without ICM was higher than normal values due to the greater number of CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, and CD14+CD16++VEGFR2+. In the bone marrow of the patients with ICM, the content of CD14++CD16-VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was lower than in patients with CAD without ICM, and the number of CD14++CD16+VEGFR2+ cells corresponded to that in the controls. Regardless of the presence of ICM in CAD, a high concentration of TNFα and normal levels of VEGF-A and IL-13 were observed in the blood. In CAD without ICM, an excess of MCP-1 and deficiency of M-CSF were revealed in the blood. In the bone marrow, the levels of VEGF-A, TNFα, M-CSF, and IL-13 were comparable between the groups of patients against the background of a decrease in the M-CSF / IL-13 ratio in the patients with ICM.Conclusion. Unlike CAD without cardiomyopathy, in ICM, no excess of VEGFR2+ cells and MCP-1 in the blood is observed, which hinders active migration of CD14+CD16++VEGFR2+ cells from the myeloid tissue, and a decrease in the M-CSF / IL-13 ratio in the bone marrow disrupts differentiation of other forms of VEGFR2+ cells, preventing vascular repair.Цель: установить нарушения дифференцировки и субпопуляционного состава VEGFR2+ моноцитов в крови и костном мозге во взаимосвязи с особенностями цитокинового профиля крови и костного мозга у больных ишемической болезнью сердца (ИБС), страдающих и не страдающих ишемической кардиомиопатией (ИКМП).Материалы и методы. В исследование вошли 74 больных ИБС, страдающих и не страдающих ИКМП (30 и 44 человека соответственно), и 18 здоровых доноров. У всех больных ИБС забор периферической крови производился непосредственно перед операцией коронарного шунтирования, а костного мозга – из разреза грудины во время операции. У здоровых доноров забирали только периферическую кровь.  В костном мозге и крови методом проточной цитофлуориметрии определяли численность VEGFR2+ моноцитов (CD14+VЕGFR2+ клеток) и их иммунофенотипов CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, CD14+CD16++VEGFR2+, CD14+CD16-VEGFR2+, методом иммуноферментного анализа регистрировали концентрацию VЕGF-А, TNFα, M-CSF, IL-13, а также содержание MCP-1 (только в крови) и соотношение M-CSF/IL-13 (только в костном мозге).Результаты. Содержание CD14+VEGFR2+ клеток в крови у больных ИБС без кардиомиопатии и с ИКМП было выше нормы из-за большей численности CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+ и CD14+CD16++VEGFR2+ форм. В костном мозге у больных ИКМП содержание CD14++CD16-VEGFR2+, CD14+CD16++VEGFR2+ и CD14+CD16-VEGFR2+ форм было ниже, чем у больных ИБС без кардиомиопатии, а количество CD14++CD16+VEGFR2+ клеток соответствовало их числу в группе сравнения. Вне зависимости от наличия ИКМП при ИБС в крови отмечалась высокая концентрация TNFα, нормальный уровень VEGF-А и IL-13; при ИБС без кардиомиопатии – избыток МСР-1 и дефицит M-CSF в крови. В костном мозге концентрация VЕGF-А, TNFα, M-CSF, IL-13 была сопоставимой между группами больных на фоне снижения M-CSF/IL-13 у пациентов с ИКМП.Заключение. В отличие от ИБС без кардиомиопатии при ИКМП не формируется избыток VEGFR2+ моноцитов и МСР-1 в крови, что затрудняет активную миграцию CD14+CD16++VEGFR2+ клеток из миелоидной ткани, а снижение M-CSF/IL-13 в костном мозге нарушает дифференцировку остальных форм VEGFR2+ моноцитов, препятствуя репарации сосудов

Production of angiogenesis mediators and the structure of the vascular wall in the heart in ischemic cardiomyopathy

Background. In the pathogenesis of ischemic cardiomyopathy (ICMP), angiopoiesis remains unexplored.The aim. To describe the vasculature of the heart and the imbalance of angiogenesis mediators in the coronary circulation in association with the number of endothelial progenitor cells (EPC) and desquamated endothelial cells (DEC) in the blood of patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Methods. Fifty-two patients with CHD (30  patients with ICMP, 22  patients without  ICMP), 15  healthy donors were examined. The content of EPC (CD14+CD34+VEGFR2+) in the blood from the cubital vein and DEC (CD45–CD146+) in the blood from the coronary sinus and the cubital vein was determined by flow cytometry. The concentrations of VEGF-A (vascular endothelial growth factor A), PDGF (platelet-derived growth factor), and SDF-1 (stromal cell-derived factor 1) in blood plasma were recorded using immunofluorescence assay; the angiopoietin-2, MMP-9 (matrix metallopeptidase 9) were recorded using enzyme immunoassay. In myocardial biopsies the specific area of vessels and the expression of αSMA (smooth muscle alpha-actin) were determined by morphometric and immunohistochemical methods.Results. In the peripheral blood of patients with CHD, regardless of the presence of ICMP, the DEC content exceeded the physiological level, and the VEGF-A, PDGF, angiopoietin-2, and MMP-9 corresponded to the norm. In CHD patients without cardiomyopathy, there was an excess of SDF-1 and EPC in the blood from the cubital vein, and in ICMP, their physiological significance was noted. In the coronary blood flow in patients with CHD without cardiomyopathy, an increase in the concentration of PDGF was found, which was not determined in patients with ICMP, who had an increased content of DEC, angiopoietin-2 and MMP-9. The specific area of the vessels in the patients of the two groups was comparable; the expression of αSMA in ICMP was 6.2 times lower than in patients with CHD without cardiomyopathy.Conclusion. The development of ICMP is accompanied by impaired maturation of vessels in the myocardium, associated with the absence of a compensatory reaction of activation of cellular and humoral factors of angiogenesis

Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins