Secretory immune system of saliva in irritable bowel syndrome on children

Background. It is known there are links between irritable bowel syndrome and development of allergy, between irritable bowel syndrome and hypoergical immunological reactions. On the other side, there is link between irritable bowel syndrome and non adequate activation of the mucosal immune system as the result of cytokin s dysbalance. That is why we investigated the secretory immune system of saliva in children with irritable bowel syndrome. The purpose of this study was to determine secretory immune system of saliva on children with different forms of irritable bowel syndrome. Methods. 102 children with irritable bowel syndrome were examined. The level of the immunoglobulins (slgA, IgA, IgG, IgM, IgE, lgG1-4), the concentration of TN F-a and lactoferrin, the total activity of the complement system (CH50) and its components (C1-C5) were obtained in the saliva. Results. It was revealed secretory immune system of saliva in children with irritable bowel syndrome was significantly differed from its of healthy children. The level of IgA, IgM in the saliva of children with irritable bowel syndrome was less than in healthy children, however, the level of IgG t-4, IgE in the saliva was significantly higher. The prevalence of the food allergy (atopy history and clinical symptoms) in children with irritable bowel syndrome was 42.2% and was differed from prevalence of the food allergy in population. Perhaps, this fact confirms the IgE-depending pathway of the irritable bowel syndrome. The saliva s level of the total activity of the complement system (CH50) and its components (C1-C5) and the concentration of TN F-a was decreased on children with irritable bowel syndrome. Also it was determined the increasing of the saliva s level of slgA, IgA, IgG, IgM, lgG1-4 was typical for the irritable bowel syndrome with abdominal pain and meteorism. The levels of some of these immune proteins in irritable bowel syndrome with diarrhea or obstipation were decreased. Conclusion Thus, these peculiarities of the secretory immunity of saliva in irritable bowel syndrome are dysregulating troubles. This fact confirms mucosal immune system takes part in development of the irritable bowel syndrome.В работе изучается характер изменений показателей секреторного иммунитета слюны у детей с синдромом раздраженного кишечника (СРК) в связи с предполагаемой связью СРК с формированием аллергии, с наличием гипзргических иммунологических реакций и напротив, с неадекватной активацией мукозальной иммунной системы в результате нарушения цитокинергической регуляции. Для проведения исследования секреторного иммунитета слюны обследовано 102 ребенка с СРК. В слюне определялось: количество иммуноглобулинов А, М. G, подклассы lg G1-4, количество slgA и IgE, активность СН50 и компонентов комплемента С1-С5, количество лактоферрина и туморнекротичский фактор TNF-a. Показатели секреторного иммунитета слюны у детей с синдромом раздраженного кишечника значительно отличаются от параметров здоровых детей. В общей группе больных детей с СРК отмечается снижение иммуноглобулинов lg A, lg М, тогда как количество IgG. Субклассов lg G1-4, IgE значительно и достоверно повышено. Происходит снижение активности отдельных компонентов комплемента и TNF-a. т.е. флогогенных факторов. Изменения показателей секреторного иммунитета слюны при синдроме раздраженного кишечника относятся к дизрегуляторным нарушениям и могут свидетельствовать об участии мукозального иммунитета в формировании данной дисфункции кишечника

The level of sex hormones and expression of hormone receptors in ovarian tissues in women with tubo-peritoneal infertility

The aim of this study was to determine the level of sex hormones and expression of receptors to them in different phases of menstrual circle in women with tubo-peritoneal infertility (TPI). Methods/data base: 100 women with TPI were investigated. Measure of hormone concentration was performed by enzyme -linked immunosorbent assay (ELISA) technique, determination of expression of receptors in ovarian tissue by immunofluorescent method. Results: The decreasing of estradiol level in serum was revealed in proliferative phase of menstrual circle in women with TPI without essential fluctuation of expression of receptors for this hormones in both phases: proliferative and secretory. The number cells with receptors for androgens were increased in active phase of chronic inflammation in ovarian glands. Conclusions: The selective decreasing of estradiol concentration in serum without changing of estradiol receptor expression in ovarian glands is one from possible mechanisms of patogenesis of estrogen insufficiency in women with TPI.Цель исследования: определить у женщин с трубно-перитонеальным беслодием (ТПБ) в разные фазы менструального цикла уровень половых гормонов в сыворотке крови и их взаимосвязь с количеством клеток в яичнике, экспрессирующих рецепторы к этим гормонам. Материал и методы: обследовано 100 женщин с трубно-перитонеальным бесплодием. Методы исследования: общеклиническое, биохимическое, микробиологическое, иммуногистохимическое, гистологическое, ПЦР диагностика. УЗИ, лапароскопия. Результаты: при лапароскопии у 88,9% пациенток с ТПБ диагностирован хронический сальпингоофорит. При исследовании гормонов в сыворотке крови в фазе пролиферации наблюдалось снижение уровня эстрадиола, при этом, существенных колебаний числа клеток в яичниках, экспрессирующих рецепторы к половым гормонам при сравнении пролиферативной и секреторной фаз цикла не наблюдалось. На фоне активности воспалительного процесса в яичниках повышается количество клеток с рецепторами к андрогенам. Выводы: при ТПБ селективно снижается содержание эстрадиола в крови и при этом не происходит изменения экспрессии рецепторов к нему в яичниках, что может лежать в основе патогенеза формирования эстрогенной недостаточности при ТПБ

Mitochondrial toxicity of triclosan on mammalian cells

Effects of triclosan (5-chloro-2’-(2,4-dichlorophenoxy)phenol) on mammalian cells were investigated using human peripheral blood mono nuclear cells (PBMC), keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine pancreatic islets (MIN-6) and neuroblastoma cells (MNA) as targets. We show that triclosan (1 – 10 μg ml-1) depolarised the mitochondria, upshifted the rate of glucose consumption in PMBC, HaCaT, PK-15 and MNA, and subsequently induced metabolic acidosis. Triclosan induced a regression of insulin producing pancreatic islets into tiny pycnotic cells and necrotic death. Short exposure to low concentrations of triclosan (30 min, ≤ 1 μg / ml) paralysed the high amplitude tail beating and progressive motility of spermatozoa, within 30 min exposure, depolarized the spermatozoan mitochondria and hyperpolarised the acrosome region of the sperm head and the flagellar fibrous sheath (distal part of the flagellum). Experiments with isolated rat liver mitochondria showed that triclosan impaired oxidative phosphorylation, downshifted ATP synthesis, uncoupled respiration and provoked excessive oxygen uptake. These exposure concentrations are 100 - 1000 fold lower that those permitted in consumer goods. The mitochondriotoxic mechanism of triclosan differs from that of valinomycin, cereulide and the enniatins by not involving potassium ionophoric activity.Peer reviewe

Tenascin-C as a cardiovascular marker

Novel biological markers, such as fibrosis marker galectin-3, peptide hormone adrenomedullin, soluble ST2, chemokine CX3CL1, surrogate marker of vasopressin, and others, are every year one step closer to being introduced into health practice. Over the past decades, significant progress has been made in the study of cardiovascular biomarkers. A key moment was the introduction of deter mining the concentration of natriuretic peptides used as markers for the diagnostic and prognostic evaluation of patients with heart failure. Currently, in order to search for novel markers for early diagnosis and risk stratification, studies have been conducted on the analysis of promising inflammatory marker tenascin-C (TNC) in cardiovascular patients. Data have been obtained that allow us to consider TNC as a tool for risk stratification and assessment of cardiovascular disease prognosis. The combination of TNC with other biological markers, in particular brain natriuretic peptide, may improve prognostic power. Nevertheless, serial testing to assess the prognosis and effectiveness of ongoing treatment, including in the conditions of a multimarker model, requires further research

A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation

Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50 % with P,0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression

Gamma-glutamyl transpeptidase is a promising biological marker of heart failure

Introduction. Currently, the search and study of new biological markers that can help early diagnosis of heart failure, serve as a laboratory tool for assessing the effectiveness of therapy, be a predictive marker of possible adverse clinical outcomes and a significant criterion for risk stratification is very relevant. While cardiospecific markers, including natriuretic peptides, their precursors, and highly sensitive troponins, are widely used in clinical practice, the need to use other markers does not have sufficient evidence. aspect of a biological marker of heart failure.Gamma-glutamyl transpeptidase is an enzyme localized on the outer side of cell membranes and involved in the metabolism of glutathione and cysteine. This enzyme is a dimeric glycoprotein (68 kDa), consisting of 2 subunits – a large and a small (46 and 22 kDa). Gamma-glutamyl transpeptidase is encoded by a multigene family consisting of at least 7 different genes located on chromosome 22; however, only 1 of these genes is involved in the formation of a functional enzyme. Gamma-glutamyl transpeptidase was found in all cells except erythrocytes. There is a significant variability in enzyme activity, which is especially high in tissues with a secretory and absorptive function, such as the kidneys, biliary tract, intestines, and epididymis.Purpose of the review is to present an overview of current publications devoted to the study of γ-glutamyl transpeptidase in the aspect of a biological marker of heart failure.Materials and methods. The analysis of literature sources (foreign and domestic articles) was carried out in the databases: PubMed, RSCI, MedLine, Google Scholar, Science Direct. The search was performed according to the following keywords: biological markers, heart failure, γ-glutamyl transpeptidase, biological markers, heart failure, γ-glutamyl transpeptidase.Results. In addition to its clinical use as a test for liver disease, biliary tract disease, and alcohol abuse, γ-glutamyl transpeptidase is of great interest because of its association with cardiovascular disease, diabetes, metabolic syndrome, and cancer. In the literature available to us, we found a small number of works devoted to the study of γ-glutamyl transpeptidase in patients with heart failure. In the review, we have presented data from experimental and clinical studies indicating a clear link between γ-glutamyl transpeptidase and heart failure. The pathogenetic mechanism of the possible relationship between γ-glutamyl transpeptidase and heart failure is not completely clear. The localization of this enzyme in tissues with a transport function has led to the assumption that it is involved in the transport of amino acids through the γ-glutamyl cycle.Conclusion. Further deeper understanding of the structure and function of the enzyme is needed, as well as future clinical studies to determine the diagnostic, prognostic and possibly therapeutic significance of this biological marker

STUDY OF THE EFFICIENCY AND SAFETY OF MYCOPHENOLATE MOFETIL THERAPY IN PATIENTSWITH SYSTEMIC SCLERODERMA

Interstitial lung disease (ILD) is one of the major causes of death in systemic scleroderma (SSD). Treatment of these patients remains difficult and controversial. Mycophenolate mofetil (MPM) has been in vitro shown to inhibit overproduction of type I collagen and hence may be effective against SSD. Objective: to study the efficiency and safety of MPM therapy in patients with SSD and clinically relevant ILD in an open-label prospective study. Subjects and methods. Ten patients with SSD (7 and 3 with its diffuse and limited forms, respectively) and ILD were given MPM in combination with glucocorticoids (mean daily dose was 10+4 mg). The mean MPM therapy duration was 11.4+1.3 months. The Rodnan total skin thickness score, flexion index, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and European Scleroderma Study Group (EScSG) activity index were estimated and a 6-minute walk test (6MWT) was carried out before and after MPM therapy. Results. After therapy, the whole group showed a significant reduction in skin scores from 12.9+9.8 to 5.6+3.2 (p=0.036) and EScSG from 3.9+1.4 to 2.25+1.03 (p=0.015) and an increase in exercise tolerance from 446+155 to 535+78 m (p=0.03) as evidenced by 6MWT. The degree of flexion contractures decreased from 15+21 to 3.7+11.3 mm (p>0.05). FVC (77.8+18.7% versus 73.8+11.3%) and DLCO (45+14.4% versus 42+16.4%) were significantly unchanged. A 10% or more clinically significant fall was noted in FVC and DLCO in 3 and 1 patients, respectively. In the remaining patients, the lung functional test results remained stable. MPM tolerability was satisfactory. All the patients completed their course of treatment. Conclusion. Stabilization of lung function with higher exercise tolerance and significantly reduced skin density allow therapy with MPM in combination with low-dose glucocorticoids to be regarded as an effective and well-tolerated treatment in patients with ILD in the presence of SS

Resistance to antihypertensive therapy in hypertensive patients. The value of the renal and hemodynamic factors

In order to assess the significance of renal, renovascular lesions and dysfunctions in the development and progression of severe and resistant to combination antihypertensive therapy (GRA), arterial hypertension (AH) in 286 patients with primary hypertension of 1-3 degrees of severity, including 105 patients from the II century, and Article III. with signs of RAG. Use the classification AG European medical societies ES HI ESC 2013 (6). In 87 patients diagnosed with hypertension 1 severity, age from 27 to 65 years, on average 49,5 ± 1,4 years, 36 men, women - 51.2 patients with hypertension severity was 82, the age from 34 to 68 years, on average 58,4 ± 3,0 years, 38 men and women - 44; AH 3 tbsp. -117 people, 49 men, women - 68, age from 42 to 72 years, on average 58,3 ± 3,8 years. Target values of blood pressure (120/80 mm Hg or less) achieved on such antihypertensive therapy in 87 patients with I st. and 29 with hypertension II degree. - They were 1 study group - PN). Partial normalization of blood pressure - a level not higher than 140/90 mm Hg It was in 65 patients (53 with hypertension II degree, and 12 with Stage III AH.) - Group 2 - CHN. In 105 patients (with Stage II St.- 34 and 83 с Stage III AH. Failed to achieve a sustainable normalization of blood pressure, even when using a 3-4 component complex antihypertensive therapy on the results of blood pressure measurements over 6-8 office hours reached 180 GARDEN and (or) diastolic blood pressure of 110 mm Hg .st. - Group 3 patients - resistant AG (RAG). Resistance for hypertension was considered in cases with SBP above 180 mmHg. Art., Dad - above 110 mm Hg. St., in the absence of normalization on the background of a complex, three-component antihypertensive therapy and the worsening of concomitant coronary, cerebrovascular and renal failure, as well as the progression of visual impairment. We performed a comprehensive study of the function and structure of the MBC, which included urine and urinary sediment analysis by Nechiporenko on Zimnitsky, renal excretion and endogenous creatinine clearance. Diagnostics included dynamic renal scintigraphy, static renal scintigraphy, ultrasound of the kidneys and of the MBC, according to testimony - excretory urography, computed tomography of the adrenal glands, aortography and renal angiography. Found that patients with resistant ongoing combination antihypertensive therapy is different from the patients with stable disease rate of violations absorptive-excretory function - secretion and excretion of one or both kidneys, without significantly reducing function azotovyvedeniya. Renal artery stenosis is 4-5 times more frequently detected in patients with stable and malignant primary hypertension than in patients with labile its passage, and all vascular lesions, including pathology of the infrarenal aorta and the renal vein, almost 2 times more often. A number of forms of congenital and acquired diseases of the renal arteries and veins (7 species) were detected only in patients with resistant hypertension. Identification of the mechanisms of renal and renovascular hypertension severe allow some patients to increase the effectiveness of antihypertensive drug therapy or to achieve complete control of blood pressure.С целью оценки значимости почечных, вазоренальных поражений и дисфункций в развитии и прогрессировании тяжелой и резистентной к комбинированной гипотензивной терапии (РАГ) артериальной гипертензии (АГ) у 286 больных с первичной АГ 1 -3 степени тяжести, в том числе у 105 больных II ст. и III ст. с признаками РАГ. Использовали классификацию АГ европейских медицинских обществ ЕОГ/ЕОК, 2013 [6]. У 87 больных диагностировали АГ 1 степени тяжести, возраст от 27 до 65 лет, в среднем 49,5+1,4 года, мужчин 36, женщин - 5 1 . Больных с АГ 2 степени тяжести было 82 .возраст от 34 до 68 лет, в среднем 58,4+ 3,0 года, мужчин 38 и женщин - 44; с АГ 3 ст. -1 1 7 человек, мужчин 49, женщин - 68,возраст от 42 до 72 лет, в среднем 58,3+3,8 года. Целевых значений уровня АД (120/80 мм рт.ст. и ниже) удалось достичь на такой гипотензивной терапии у 87 больных I ст. и у 29 с АГ II ст. - они составили 1 группу исследования - ПН). Частичная нормализация АД - с уровнем не выше 140/90 мм рт.ст. была у 65 больных ( у 53 с АГ II ст. и у 12 с АГ III ст.) - 2 группа - ЧН. У 105 больных (с АГ II ст.- 34 и у 83 с АГ III ст. не удалось добиться устойчивой нормализации АД, даже при использовании 3-4 компонентной комплексной гипотензивной терапии уровень АД по результатам 6-8 офисных измерений за сутки достигал САД 180 и (или) ДАД 110мм рт .ст.- 3 группа больных - резистентной АГ (РАГ). Резистентным течение АГ считали в случаях с уровнем сАД выше 180 мм рт. ст., дАД - выше 110 мм рт. ст., при отсутствии нормализации на фоне проводимой комплексной, трехкомпонентной гипотензивной терапии и ухудшении течения сопутствующей коронарной, цереброваскулярной и почечной недостаточности, а также при прогрессировании нарушений зрения. Выполняли комплексное исследование функции и структуры органов МВС, которое включало исследование мочи и мочевого осадка, анализ по Нечипоренко, по Зимницкому, почечное выведение и клиренс эндогенного креатинина. Инструментальная диагностика включала динамическую сцинтиграфию почек, статическую сцинтиграфию почек, ультразвуковое исследование почек и органов МВС, по показаниям - экскреторную урографию, компьютерную томографию надпочечников, аортографию и ангиографию сосудов почек. Установили, что больных с резистентных к проводимой комбинированной гипотензивной терапией, отличала от больных со стабильным течением заболевания частота нарушений поглотительно-выделительной функции - секреции и экскреции одной или двух почек, без существенного снижения функции азотовыведения. Стенозы почечных артерий в 4-5 раз чаще выявлялись у больных со стабильной и злокачественной первичной гипертензией, чем у больных с лабильным ее течением, а все сосудистые поражения, включая патологию инфраренального отдела аорты и почечных вен, почти в 2 раза чаще. Целый ряд форм врожденной и приобретенной патологии почечных артерий и вен (7 видов) выявлялись только у больных с резистентной гипертензией. Идентификация вазоренальных и нефрогенных механизмов тяжелой артериальной гипертензии позволяла у части больных повысить эффективность медикаментозной гипотензивной терапии или добиться полного контроля АД

Hypotensive therapy of arterial hypertension in chronic limb ischemia and acute thrombotic occlusion

The aim of the investigation was to evaluate the efficacy and safety of the treatment of arterial hypertension syndrome in patients with peripheral arterial disease of the lower and upper extremities and to analyze the efficiency of the effect of operative revascularization of the limb arteries on the course of arterial hypertension.Цель исследования – оценить эффективность и безопасность лечения синдрома артериальной гипертензии у больных с заболеваниями периферических артерий нижних и верхних конечностей и проанализировать эффективность воздействия оперативной реваскуляризации артерий конечностей на характер течения артериальной гипертензии