Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking

The aim of this pilot study was to investigate whether single nucleotide polymorphisms in the gene encoding the catalytic subunit of glutamate cysteine ligase are associated with the risk and clinical features of psoriasi

Effect of erythropoietin on bone marrow mononuclear cells

Stem/progenitor cells are considered an alternative method of heart failure therapy by promoting regeneration of damaged myocardium in myocardial infarction. Effectiveness of cell therapy depends on the population composition and functional activity of the cell graft, and, in turn, it depends on the conditions of microenvironment. Cultivation of stem/progenitor cells with erythropoietin stimulates proliferative potential causing in vitro resistance to hypoxia, and in vivo stimulation of angiogenesis. We aimed for assessing effects of erythropoietin upon hematopoietic cells. We studied some effects of short-term incubation of bone marrow mononuclear cells (BM-MNCs) in patients with coronary heart disease (CHD) with erythropoietin upon cellular phenotype, cell cycle, apoptosis and their proliferative potential. BM-MNCs were isolated from bone marrow aspirate from patients with CHD in a density gradient, then incubated for 60 minutes with erythropoietin (33.4 IU/ml). Using flow cytometric assay of the total BM-MNCs pool, we have shown there endothelial progenitor cells at different stages of maturation and differentiation, mesenchymal stem cells are. Their total number did not exceed 30%. Short-term incubation of BM-MNCs with erythropoietin reduces expression of CD184 “homing receptor” molecules on CD34+ cells, and causes increase of CD184 on CD31+ cells in the BM-MNCs pool (p < 0.05). In addition, erythropoietin has been shown to cause a delay of CD34+ cells in the resting phase (G0G1), reduce a proportion of cells in the synthetic phase (S) and mitosis (G2/M) (p<0.05), and does not affect apoptosis, as shown by Annexin V-FITC Apoptosis Detection Kit. Erythropoietin had no significant effects on expression on BM-MNCs surface molecules involved in providing adhesion, such as CD18, CD29, CD44, CD49a, CD54, CD62E, CD146, and CD202b. MTT-method has shown that the short-term preincubation of BM-MNCs with erythropoietin contributed to a significant decrease in proliferative activity of BM-MNCs (p < 0.05). However, there was a tendency towards increased resistance of erythropoietin-pretreated BM-MNCs to oxidative stress induced by hydrogen peroxide. We have also revealed a correlation between the numbers of endothelial progenitor cells at different stages of differentiation, and numbers of hematopoietic stem cells in the total BM-MNCs pool. The number of CD34+/CD133+, CD34- / CD31+, CD45+/EpoR+, and CD34+/EpoR+ in BM-MNCs pool are dependent on the age of patients. Hence, a short-term incubation of BM-MNCs with erythropoietin promotes the cells to be retained in resting phase of the cell cycle, thus, in turn, helping to reduce proliferative potential of BM-MNCs

EFFECT OF ERYTHROPOIETIN ON CYTOKINE PRODUCTION BY STEM CELLS

Erythropoietin (EPO) is mainly used to stimulate erythropoiesis. Its cytoprotective effects upon other cells of the human body and animals were recently shown, in particular, anti-apoptotic effect was observed. EPO effect upon the cells is mediated by interaction with erythropoietin receptor, with a complex forming a heterodimeric bond with β-common chain (CD131). In the present work, we studied the changes in erythropoietin receptor expression, and production spectrum of biologically active molecules in bone marrow mononuclear cells (BM-MNC) of patients with coronary heart disease. The flow cytometric assays showed that short-term incubation of BM-MNC with erythropoietin caused increased expression of the erythropoietin receptors on hematopoietic stem cells and tended to reduce the number of endothelial progenitor cells carrying the erythropoietin receptors. Solid-phase enzyme immunoassay in conditioned media from BM-MNC revealed that long-term (72 hours) exposure of BM-MNC to erythropoietin promoted increased production of IL-1β, PDGF-AB, and Epo, if compared to the basal production level (p < 0.05). Short-term incubation of BM-MNC with erythropoietin (60 minutes) caused a significant increase in the IL-1β, PDGF-AB and CXCL-12 / SDF-1α production levels, as well as significant reduction in the IL-10 production levels compared to the basal levels (p < 0.05)

Modern anatomical and physiological bases for maintaining the transparency of the corneal stroma

The article presents a literature review of the modern concept of anatomical and physiological structure and functioning of the cornea. The strict morphological structure and corneal tissue homeostasis ensure its transparency. Studying the mechanisms that regulate the constancy of the corneal tissue internal environment allows us to get closer to understanding the prospects forregenerative therapy for the corneal stroma pathology. The article discusses in detail the role and functional potential of corneal stromal cells, which are capable of reverse cytologic differentiation, which primarily ensures the maintenance of tissue homeostasis and corneal transparency. The functional activity of corneal cells can change for a number of reasons, which may be exogenous, iatrogenic (trauma, infection, etc.) or endogenous. Endogenous causes include: cell autoregulation pathologies (for example, enzyme defects); defects in transport systems leading to tissue hypoxia; disorders of the neuro-humoral regulation of trophism. The physical reason forthe violation of the corneal transparency is an increase in the light scattering. The article presents five main causes of increased light scattering in the opaque cornea, and also provides an overview of the main substances – components and products of cellular synthesis of corneal stromal cells: cytokines and growth factors (complex of the signal molecule and the SDF1/CXCR4 receptor, insulin-like growth factor 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, erythropoietin, neurotrophic factors, etc.). Thus, corneal opacity can be caused by a single pathogenic mechanism or be the result of a complex effect of several factors. The main processes of tissue homeostasis regulation are aimed at maintaining the unique morphological structure of the cornea

Clinico-laboratorial characteristic of acute enteric infection of tender-aged children.

The article presents the results of clinical and laboratory examination of 123 young children with viral and mixed etiology infections. The analysis of the age structure of children, as well as the frequency of occurrence of conditionally pathogenic flora in viral-microbial associations, was made.В статье представлены результаты клинико-лабораторного обследования 123 детей раннего возраста с инфекцией вирусной и смешанной этиологии. Произведен анализ возрастной структуры детей, а также частоты встречаемости условно-патогенной флоры в вирусно-микробных ассоциациях

Features of bronchial asthma combined with gastroesophageal reflux

the article presents the results of clinical, laboratory and instrumental examination of 46 school-age children with bronchial asthma and gastroesophageal reflux disease. The absence of significant features of bronchial asthma against the background of gastroesophageal reflux disease was revealed. The importance of including fibrogastroduodenoscopy in the examination plan of a patient with bronchial asthma is shownв статье представлены результаты клинико-лабораторного и инструментального обследования 46 детей школьного возраста с бронхиальной астмой и гастроэзофагеальной рефлюксной болезнью. Выявлено отсутствие значимых особенностей течения бронхиальной астмы на фоне гастроэзофагельной рефлюксной болезни. Показано значение включения фиброгастродуоденоскопии в план обследования пациента с бронхиальной астмо

Assessment of the degree of dehydration in infectious gastroenteritis in young children

The article discusses two ways to determine the severity of the condition in infectious gastroenteritis. The possibility of using the VESIKARI scale for assessing the condition in children is being determined.В статье рассматривается два способа определения степени дегидратации при инфекционных гастроэнтеритах. Определяется возможность использования шкалы VESIKARI для оценки состояния у детей

Нейрореспираторный синдром у больных бронхиальной астмой

Personal features, cerebral bioelectrical activity, vegetative regulation, bronchial hyperreactivity and lung function regulation were analyzed in 219 bronchial asthma patients. The detected disorders allowed to characterize two-staged neuro-respiratory disadaptation syndrome. The mild disorders (the 1st stage) are described as adjusting overwork of neuro-regulatory systems. More severe disorders (the 2nd stage) are less adaptive and enhance the disease resulting in ventilation disorders and bronchial hyperreativity.У 219 больных бронхиальной астмой проанализированы особенности личности, биоэлектрической активности мозга, вегетативной регуляции, бронхиальной гиперреактивности и регуляции внешнего дыхания. Выявленные нарушения позволили выделить синдром нейрореспираторной дезадаптации, в течении которого выявлена этапность. При легком течении заболевания (первый этап) обнаружено напряжение нейрорегуляторных систем, носящее в основном адаптивный характер. При более тяжелом течении заболевания (второй этап) выявлены нарушения, которые носят не столько приспособительный характер, сколько усугубляют течение болезни и приводят к нарушению вентиляции легких и бронхиальной гиперреактивности

Особенности субпопуляционного состава дендритных клеток у больных ревматоидным артритом

Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Dendritic cells (DCs) as the main antigen-presenting cells play an important role in the pathogenesis of RA. There are two major DC populations: myeloid and plasmacytoid DCs (mDCs and pDCs). B cells as antibody-producing cells also play an important role in the pathogenesis of RA. The probability of achieving low disease activity and clinical and laboratory remission has been proven to be maximal in the very early period of the disease and in the patients who have not been previously prescribed disease-modifying antirheumatic drugs (DMARDs). In this connection, it is necessary to elaborate additional criteria and biomarkers for early RA.Objective: to investigate the subpopulation composition of DCs in patients with early-stage RA.Patients and methods. The investigation enrolled 60patients with RA who met the 2010 ACR/EULAR and the 1987ACR criteria. The patients with RA were divided into two groups: 1) 30patients with early RA (the disease duration was not more than 1 year); 2) 30 patients with advanced RA. A control group consisted of 30 patients with osteoarthritis (OA) who met the ACR criteria. All the patients with RA were treated with DMARDs. The patients with early RA had not previously received DMARDs; after being included in the study, they were prescribed methotrexate 15-20 mg/week. The patients with advanced RA took methotrexate 15-25 mg/week (n=24), sulfasalazine 2 g/day (n=5), or leflunomide 20 mg/day (n=1).At the first stage, the levels of different subpopulations of DCs and B lymphocytes were studied in the patients with early RA before initiation of therapy and in those with advanced RA and in the control persons. At the following stage, the time course of changes was investigated in the subpopulation composition of DCs and B lymphocytes during therapy.Results and discussion. The subpopulations of peripheral blood DCs in early RA were characterized. A subpopulation of mDCs was shown to dominate in the patients with early RA versus those with advanced RA or osteoarthritis (OA). In addition, the patients with RA showed a high B lymphocyte level. It was noted that there was no significant differences in the level of pDCs between RA and OA patients and there was an inverse relationship between the relative peripheral blood level of pDC and disease activity, which confirms the immunosuppressive role of pDCs in the pathogenesis of RA. The levels of mDCs and B lymphocytes during DMARD therapy were ascertained to significantly decrease to those seen in healthy donors.Conclusion. Thus, the findings suggest that the number of mDCs and B lymphocytes increases in patients with early RA, unlike those with OA. In addition, the change in the number of mDCs and B cells during therapy is associated with the dynamics of disease activity and may suppose that mDCs are a target for the action of DMARDs.Ревматоидный артрит (РА) является одним из наиболее распространенных ревматических заболеваний. Дендритные клетки (ДК) играют важную роль в патогенезе РА как основные антиген-презентирующие клетки. Выделяют две основные популяции ДК: миелоидные (мДК) и плазмоцитоидные (пДК). Также важную роль в патогенезе РА играют В-клетки как клетки-антителопродуценты. Доказано, что вероятность достижения низкой активности и клинико-лабораторной ремиссии максимальна в самом раннем периоде заболевания и у тех пациентов, которым базисные противовоспалительные препараты (БПВП) ранее не назначали. В связи с этим необходима разработка дополнительных критериев, а также биомаркеров раннего РА.Цель исследования — изучить субпопуляционный состав ДК у больных РА на ранних стадиях заболевания.Пациенты и методы. В исследование включено 60 пациентов с РА, соответствующих критериям ACR/EULAR 2010 г. и ACR 1987 г. Пациенты с РА были разделены на две группы: в 1-ю группу вошли больные с ранним РА (длительность заболевания не более 1 года, n=30), во 2-ю — с развернутым РА (n=30). Контрольную группу составили 30 пациентов с остеоартритом (ОА), соответствующих критериям ACR. Всем пациентам с РА проводили терапию БПВП. Пациенты с ранним РА ранее не получали БПВП, после включения в исследование им был назначен метотрексат 15—20 мг/нед. Пациенты с развернутым РА получали метотрексат по 15—25мг/нед (n=24), сульфасалазин 2 г/сут (n=5) или лефлуномид 20мг/сут (n=1).На первом этапе проведено исследование уровня различных субпопуляций ДК, а также В-лимфоцитов у пациентов с ранней стадией РА до начала терапии, а также у пациентов с развернутым РА и в контрольной группе. На следующем этапе была изучена динамика субпопуляционного состава ДК и В-лимфоцитов на фоне терапии.Результаты и обсуждение. Охарактеризованы субпопуляции ДК периферической крови при раннем РА. Показано, что у пациентов с ранним РА, в отличие от пациентов с развернутым РА и остеоартритом (ОА), наблюдается доминирование субпопуляции мДК. Кроме того, пациенты с РА характеризуются высоким уровнем В-лимфоцитов. Отмечено отсутствие значимых различий в уровне пДК между пациентами с РА и ОА, также выявлена обратная связь между относительным содержанием пДК в периферической крови и активностью заболевания, что подтверждает иммуносупрессивную роль пДК в патогенезе РА. Установлено значимое снижение содержания мДК и В-лимфоцитов на фоне терапии БПВП до уровня здоровых доноров.Выводы. Таким образом, полученные данные свидетельствуют об увеличении числа мДК и В-лимфоцитов у пациентов с ранним РА в отличие от пациентов с ОА. Кроме того, изменение количества мДК и В-клеток на фоне терапии ассоциировано с динамикой активности заболевания и позволяет предположить, что мДК являются мишенью для воздействия БПВП