FEATURES OF SYSTEM IMMUNITY IN WOMEN WITH ENDOMETRIOSIS AND GENITAL INFECTION

External genital endometriosis is an inflammatory, estrogen-dependent disease that develops predominantly in women of reproductive age and is characterized by the presence of pain syndrome and infertility. Today, endometriosis is one of the most common gynecological diseases in women of reproductive age, however, the etiology and pathogenesis of it are not completely clear. Violations of systemic immunity are most important in the pathogenesis of endometriosis. The literature data on the features of the immune response in endometriosis in combination with genital infection are few and contradictory. Purpose – to study the features of systemic immunity in women with external genital endometriosis and pathogens of genital infection.A total of 159 women with external genital endometriosis were examined. The main lymphocyte subpopulations, the functional activity of neutrophils and peripheral blood monocytes, and the content of cytokines in the blood serum were studied. A study of systemic immunity was performed in women with 1-2 and 3-4 stages of endometriosis, as well as depending on the presence of pathogens of genital infection. The presence of Chlamydia trachomatis, Ureaplasma spp., Mycoplasma genitalium, HSV1, 2/CMV, HPV in the endometrium, peritoneal fluid, and endometrioid heterotopies was determined. Statistical processing was performed using the IBM SPSS Statistics Version 22.2 statistical analysis software package.According to the results of the study, it was found that women with endometriosis of stages 1-2 show signs of systemic inflammation with a predominance of the Th2 type of immune response and inhibition of cellular immunity. A particular feature of HPV was an increase in T-NK lymphocytes, a decrease in IL-2 and neutrophil functional activity. The presence of Ureaplasma spp./Mycoplasma genitalium was characterized by a decrease in cellular immunity and an increase in T-NK cells. Only with HPV and Ureaplasma spp./Mycoplasma genitalium decreased synthesis of IL-2, IL-6. With 3-4 stages, the most significant changes in immunity were found in groups of women with genital infection. When HPV – a high level of IgA, increased IgM, IL-8. With Ureaplasma spp./Mycoplasma genitalium – inhibition of cellular immunity, high levels of IgA, reduction of neutrophil phagocytic activity.Thus, in women with endometriosis in the presence of pathogens of genital infection revealed features that may contribute to the development and progression of the disease

Triggers and markers of skin aging in women with menopausal syndrome

Introduction. External manifestations of aging, and especially skin aging are the most important for modern women.Aim. The aim of our study was to identify a set of adverse factors that effect on the skin of women in menopausal transition (MP) and in postmenopause (PM), and to identify markers of skin aging in this category of women.Materials and methods. The study included 36 women in MP and PM suffering from MS. At the first stage, anamnesis was collected, anthropometric data and severity of MS were evaluated, and the hormonal profile of patients was determined. At the second stage, computer mapping of the skin was performed using the digital video camera Aramo SG with the skin XPpro program. Statistic analysis was performed using the SPSS v13.0 program. Spearman’s analysis was used to determine the relationship between anthropometric, clinical and anamnestic data and the measurements of skin condition of women in MP and PM. Results. According to the obtained data, the main triggers of skin aging of women in MP and PM are: the presence of metabolic disorders (obesity, metabolic syndrome), decrease of estradiol and progesterone levels in blood serum as well as increase of prolactin level and rhythm disturbance of melatonin secretion. Markers of skin aging in women with menopausal syndrome are decreased moisture, increased oiliness in T-zone, increased of skin pigmentation and enlarged pore size.Conclusions. The obtained data are useful for management involuting skin changes of women in PM and MP suffering from MS. The data justifies the relevancy to normalization not only the estradiol level, but other sex steroids, melatonin, as well as correction of metabolic endocrine processes, and treatment of MS

Relationships between serum HMGB1 concentration and subpopulation composition of circulating monocytes in patients with subclinical atherosclerosis

Chronic non-infectious inflammation of low intensity is the most important mechanism of development and progression in atherosclerosis. Under the conditions of persistent non-resolving inflammation observed in the vascular wall and atherosclerotic plaque (ASB), permanent tissue damage occurs, thus leading to increased formation of endogenous danger-associated molecular patterns (DAMPs). The non-histone chromosomal protein HMGB1 may be regarded as a prototypical DAMPs. HMGB1 acts as a DAMP if entering the extracellular space, causing inflammation by its binding to pattern-recognizing receptors (TLR2, TLR4, RAGE, CD36, etc.). A number of clinical studies have revealed higher HMGB1 levels in the blood of patients with coronary heart disease and atherosclerotic disease of the lower limb arteries, as well as its interrelations with the burden of coronary artery atherosclerosis. Currently, the mechanisms of HMGB1-mediated atherosclerosis progression are studied only fragmentary. The aim of our study was to investigate relationships between the serum HMGB1 level and subsets of circulating monocyte subpopulations in patients with subclinical atherosclerosis.The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Serum HMGB1 concentration was determined using enzyme immunoassay kits (Human HMGB1/HMG-1 ELISA Kit, NBP2-62766, Novus Biologicals, USA). The serum HMGB1 threshold was 18.75 pg/ml, whereas the measurement range was 31.25 to 2000 pg/ml. Phenotyping of the blood monocyte subpopulations was performed by flow cytometry using Navios 6/2 device (Beckman Coulter, USA).An increase in serum HMGB1 concentration was associated with decreased number of classical M2 monocytes, and an increase in intermediate and M1 monocytes. Moreover, an increase in HMGB1 concentration was associated with higher numbers of classical, intermediate, and non-classical monocytes expressing CD36 and TLR2. Increased HMGB1 concentration (from Q1 to Q4) correlated with higher numbers of classical (p = 0.001) and intermediate monocytes (p = 0.006) but not with non-classical phenotypes (p = 0.147). Upon increase of HMGB1 concentration (Q1 to Q4), we have found an increase in the number of classical (p < 0.0001), intermediate (p < 0.0001), and non-classical (p < 0.0001), CD36-expressing monocytes. An increased number of intermediate (p = 0.022; p1, 4 = 0.034) and non-classical, TLR2-expressing monocytes was also revealed (p = 0.002; p1, 4 = 0.035). By mean of correlation analysis, IL-1β concentrations showed direct correlation with the number of M1 monocytes (r = 0.268; p = 0.035) and inverse relation with the number of M2 monocytes (r = -0.376; p = 0.003).Increased serum HMGB1 concentration in patients with subclinical atherosclerosis was associated with decreased numbers of classical and M2 monocytes, as well as higher numbers of intermediate and M1 monocytes, like as with increased contents of intermediate and non-classical monocytes expressing CD36 and TLR2. IL-1β levels directly correlated with HMGB1 concentration and the number of Mi-monocytes

Interactions between immunosuppressor neutrophiles, innate and adaptive immunity indexes in the patients with subclinical atherosclerosis

The last fifteen years have been marked by rapid progress in the study of neutrophils. The discovery of transcriptional plasticity of neutrophils, their phenotypic and functional heterogeneity contributed to launching active interdisciplinary studies on the role of neutrophils in various chronic inflammatory diseases. Increased systemic circulation of immunosuppressive neutrophils can be observed not only in sepsis, but also in chronic systemic inflammation, which, along with disorders of lipid metabolism, is the major mechanism of atherosclerosis development and progression. Monocytes, dendritic cells, Tlymphocytes and neutrophils are key participants and modulators of inflammation in atherosclerosis. Potential significance of immunosuppressive neutrophils in atherogenesis and regulation of inflammatory response in atherosclerosis has not been currently established. However, taking into account their possible effects upon T lymphocytes and innate immunity cells, the study of immunosuppressive neutrophils seems promising in the context of atherosclerosis and atherosclerotic cardiovascular diseases. The purpose of this study was to evaluate relationship between the numbers of circulating immunosuppressive neutrophils and subpopulations of T cells and monocytes in the patients with subclinical atherosclerosis. The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Subpopulations of neutrophils, lymphocytes and monocytes were phenotyped by flow cytometry using “Navios 6/2” (Beckman Coulter). 133 patients, 65 (48.8%) males and 68 (51.2%) females were included into the study. Correlation analysis showed that increased number of circulating CD16hiCD11bloCD62Lbr neutrophils was associated with increased number of regulatory T lymphocytes. The patients with subclinical atherosclerosis and absolute numbers of circulating immunosuppressive neutrophils within the first quartile (<136 cells/μL) had a statistically significantly lower number of regulatory T lymphocytes compared with patients in the 2-4 quartiles. An increase in immunosuppressive neutrophils was associated with decreased number of classical monocytes expressing TLR4 (r = -0.335; p = 0.004), and a decrease in TLR2 surface expression intensity (r = -0.268; p = 0.023) on the non-classical monocytes. In patients with subclinical atherosclerosis of 40-64 years old, an increase in immunosuppressive CD16hiCD11bloCD62Lbr neutrophils was associated with increase in regulatory T lymphocytes and nonclassical monocytes, as well as decrease in classic monocytes expressing TLR4, and lower intensity of TLR2 expression on the non-classical monocytes

Assessment of the immune status of women after ablative fractional laser photothermolysis procedure for the correct of involutional facial skin changes

The aim of the work was to evaluate in dynamics the response of the immune system to the A-FLPh procedure performed for correction of age-associated facial skin changes.Цель работы – оценить в динамике реакцию иммунной системы на процедуру А-ФЛФ, проведенную для коррекции возраст-ассоциированных изменений кожи лица

Neurobiological (genetic and immunological) markers of autism spectrum disorders (review)

The relevance of the study of autism spectrum disorders (ASD) is due to the high incidence of 50-116 cases per 10 000 child population, the lack of precise knowledge of the etiology and pathogenesis, insufficient development issues of therapy and correction, which makes it necessary to search for specific neurobiological markers: genetic, immunological. Currently, there are various hypotheses etiology of ASD: biological, psychological, which are not mutually exclusive, and describe the simultaneous effect of various etiological factors.Актуальность изучения расстройств аутистического спектра (РАС) определяется высокой распространенностью до 50-116 случаев на 10 ООО детского населения, отсутствием точных знаний об этиологии и патогенезе, недостаточной разработанностью вопросов терапии и коррекции. Все это делает необходимым поиск специфических нейробиологических маркеров: генетических, иммунологических. В настоящее время существуют различные гипотезы этиологии РАС: биологические, психологические, которые не исключают друг друга, а описывают одновременное влияние различных этиологических факторов

Immunological indicators at children with autism spectrum disorders

Presents the results of a study on indicators of immunity 96 in children aged 3 to 11 years with autism spectrum disorders. The study of immunity by flow cytopfuorometry showed the highest number of leukocytes in peripheral blood is typical for children with delays in language development and autistic behavior, and for patients with Kanner syndrome increase in the absolute number of T-cytotoxic and limfocitopodobnye NK cells that may be indicative of immune activation. Of the results of the study of humoral immunity showed that in children with atypical autism IgA is higher but does not exceed the reference values. The data obtained can expand understanding of the nature of autism spectrum disorders involving the immune system, to objectify the condition of the nervous system, and enable the development of pathogenetic approaches to the treatment.Представлены результаты исследования показателей иммунитета у 96 пациентов в возрасте от 3 до 11 лет с РАС. Изучение клеточного иммунитета показало наибольшее количество лейкоцитов в периферической крови у детей с задержками развития речи и аутистическим поведением, у пациентов с синдромом Каннера повышение абсолютного количества Т-цитотоксических и лимфоцитоподобных NK клеток, что может свидетельствовать об активации иммунитета. В показателях гуморального иммунитета у детей с атипичным аутизмом IgA выше, но не выходит за пределы референсных значений. Полученные данные могут расширить представления о природе расстройств аутистического спектра, участие иммунной системы в данных нарушениях, объективизировать состояние нервной системы и позволят разработать патогенетические подходы в терапии

Эхогенность каротидных атеросклеротических бляшек как предиктор неблагоприятных сердечно-сосудистых событий у пациентов 40–64 лет: проспективное исследование

INTRODUCTION: Noninvasive assessment of carotid atherosclerotic plaque (CAP) morphology represents a promising direction, allowing to optimize not only cardiovascular event risk assessment, but also the selection of patients for carotid revascularization. Determination of CAP echogenicity by means of GSM-analysis can be used as part of multiparametric assessment of CAP instability and prediction of adverse cardiovascular events.OBJECTIVE: To assess the predictive value of echogenicity of carotid atherosclerotic plaques in relation to the development of adverse cardiovascular events in patients 40–64 years old.MATERIALS AND METHODS: The study included 191 patients with carotid atherosclerosis aged 40–64 years. All patients underwent duplex scanning of the arteries of the carotid basin with determination of the echogenicity of carotid ASBs. The combined end point (CEP) consisted of the following possible events: nonfatal myocardial infarction or unstable angina, nonfatal stroke, coronary revascularization or peripheral artery revascularization, and death from cardiovascular causes. Data on the onset of CVD were collected during follow-up visits and using medical information systems. Statistics: Data were analyzed using MedCalc software (version 20.216). Frequencies and percentages were used to describe nominal data, and medians and quartiles were used for quantitative data. The Kaplan-Meier survival analysis method was used to estimate the probability of events constituting the combined endpoint. Cox regression analysis was used to estimate the risk of the event and the influence of independent variables on the risk.RESULTS: By correlation analysis, carotid AP echogenicity (GSM) was inversely correlated with BMI (r=-0,355; p<0,0001), waist circumference (r=-0.37; p<0.0001), triglyceride levels (r=-0.163; p=0.027), uric acid (r=-0.188; p=0.028). The duration of the follow-up period was 15.1 (12.2; 22.9) months. Events constituting CEP occurred in 15 (7.85%) patients: nonfatal myocardial infarction in 2 (1.05%) patients, nonfatal stroke in 2 (1.05%) patients, myocardial revascularization in 6 (3.14%) patients, unstable angina in 5 (2.61%) patients. The presence of carotid AP with echogenicity ≤39 conventional units allowed predicting the development of events constituting CEP with sensitivity of 53.3% and specificity of 80.7%. Kaplan-Meier survivalanalysis revealed that cumulative survival of patients with carotid AP with echogenicity ≤39 conventional units was statistically significantly lower compared to patients with carotid ASB with echogenicity >39 conventional units.DISCUSSION: It should be noted that in the presented study, decreased echogenicity of carotid AP was associated with the risk of adverse cardiovascular events only in the simple and sex- and age-adjusted models, but not in the full-adjusted model. It is likely that this may be due to the fact that the echogenicity of CAP is closely related to the cumulative burden of cardiovascular risk factors, which has been shown in earlier studies including. Probably, combined assessment of carotid atherosclerosis burden and morphological features of CAP may be the most promising approach to obtain additional prognostic information in patients with carotid atherosclerosis.CONCLUSION: Among patients with carotid atherosclerosis 40–64 years old, the presence of ACS with echogenicity ≤39 conventional units was associated with a 3.44 (95% CI 1.19–9.91) fold increase in the relative risk of events constituting the combined endpoint after adjusting for sex and age.ВВЕДЕНИЕ: Неинвазивная оценка морфологии каротидных атеросклеротических бляшек (АСБ) представляет собой перспективное направление, позволяющее оптимизировать не только оценку риска сердечно-сосудистых событий, но и отбор пациентов для реваскуляризации сонных артерий. Определение эхогенности АСБ посредством GSM-анализа может быть использовано в рамках мультипараметрической оценки нестабильности АСБ и прогнозирования неблагоприятных сердечно-сосудистых событий.ЦЕЛЬ: Оценить предиктивную ценность эхогенности каротидных атеросклеротических бляшек в  отношении развития неблагоприятных сердечно-сосудистых событий у пациентов 40–64 лет.МАТЕРИАЛЫ И  МЕТОДЫ: В  исследование был включен 191 пациент с  каротидным атеросклерозом в  возрасте 40–64 лет. Всем пациентам проводили дуплексное сканирование артерий каротидного бассейна с определением эхогенности каротидных АСБ. Комбинированная конечная точка (ККТ) состояла из  следующих возможных событий: нефатальный инфаркт миокарда или нестабильная стенокардия, нефатальный инсульт, коронарную реваскуляризацию или реваскуляризацию периферических артерий, смерть от сердечно-сосудистых причин. Сбор данных о наступлении ККТ, проводили во время повторных визитов и с помощью медицинских информационных систем.Статистика: Анализ данных проводили с помощью программного обеспечения MedCalc (версия 20.216). Для описания номинальных данных использовали частоты и проценты, для количественных данных медиану и квартили. Для оценки вероятности развития событий, составляющих комбинированную конечную точку, применяли метод анализа выживаемости Каплана–Майера. С целью оценки риска наступления события и влияния независимых переменных на указанный риск применяли регрессионный анализ Кокса.РЕЗУЛЬТАТЫ: По результатам корреляционного анализа эхогенность каротидных АСБ (GSM) обратно коррелировала с ИМТ (r=–0,355; p<0,0001), окружностью талии (r=–0,337; p<0,0001), уровнем триглицеридов (r=–0,163; p=0,027), мочевой кислотой (r=–0,188; p=0,028). Длительность периода наблюдения составляла 15,1 (12,2; 22,9) мес. События, составляющие ККТ, произошли у 15 (7,85%) пациентов: нефатальный инфаркт миокарда — у 2 (1,05%) пациентов, нефатальный инсульт — у 2 (1,05%), реваскуляризация миокарда — у 6 (3,14%), нестабильная стенокардия — у 5 (2,61%) пациентов. Наличие каротидных АСБ с эхогенностью ≤39 усл.ед. позволяло прогнозировать развитие событий, составляющих ККТ, с чувствительностью 53,3% и специфичностью 80,7%. По результатам анализа выживаемости Каплана–Мейера было установлено, что кумулятивная выживаемость пациентов, имеющих каротидные АСБ с  эхогенностью ≤39 усл.ед., была статистически значимо ниже, в сравнении с пациентами, имеющими каротидные АСБ с эхогенностью >39 усл.ед.ОБСУЖДЕНИЕ: Необходимо отметить, что в представленном исследовании снижение эхогенности каротидных АСБ было связано с  риском неблагоприятных сердечно-сосудистых событий только в  простой модели и  модели с  поправкой на  пол и возраст, но не в модели с полной поправкой. Вероятно, это может быть связано с тем, что эхогенность АСБ тесно связана с кумулятивным бременем кардиоваскулярных факторов риска, что было показано в том числе в более ранних исследованиях. Вероятно, комбинированная оценка бремени каротидного атеросклероза и морфологических особенностей АСБ может быть наиболее перспективным подходом к получению дополнительной прогностической информации у пациентов с каротидным атеросклерозом.ЗАКЛЮЧЕНИЕ: Среди пациентов с каротидным атеросклерозом 40–64 лет наличие АСБ с эхогенностью ≤39 усл. ед. ассоциировалось с  увеличением относительного риска развития событий, составляющих комбинированную конечную точку в 3,44 (95% ДИ 1,19–9,91) раза после поправки на пол и возраст

STUDIES OF SYSTEMIC AND LOCAL CYTOKINE LEVEL IN RETINAL VEIN OCCLUSION ASSOCIATED WITH ANTIANGIOGENIC THERAPY

The paper presents results of studying systemic and local level of cytokines in retinal vein occlusion following antiangiogenic therapy. The study of cytokine concentrations was conducted in the general group of patients, and depended on the type of retinal vein occlusion before and after intravitreal injections of Ranibizumab. We examined thirty-two patients with retinal vein occlusion. We performed standard ophthalmological examinations, spectral optical coherence tomography, fluorescent angiography in order to establish the type of retinal vein occlusion. We determined concentration of vascular endothelial growth factor (VEGF), endothelin-1, interleukin-1, interleukin-6 and tumor necrosis factor-α in serum and tears by enzyme immunoassay before treatment, and 3 months after regular injections of Ranibizumab. The obtained data prove that all the patients with retinal vein occlusion had significantly increased VEGF levels in blood serum and tear fluid compared to the control group. We have revealed a positive correlation between levels of VEGF in tear fluid, and interleukin-1, interleukin-6 and endothelin-1 in the tears, as well as with VEGF concentrations and endothelin-1 in serum. We have found an increase of endothelin-1 in tear and serum, alongd with interleukins and tumor necrosis factor-α in tear fluid, with maximal concentrations of some factors in ischemic type of retinal vein occlusion. Following antiangiogenic therapy in patients with non-ischemic type, there was a significant decrease in VEGF level, interleukin-6 and tumor necrosis factor-α in the serum, vascular endothelial growth factor and interleukin-1 in tears. In patients with ischemic type, a significant decrease in VEGF and interleukin-6 concentrations in tears, endothelin-1 and interleukin-1 in blood serum. Thus, our research showed the role of interleukins, tumor necrosis factor-α, vascular endothelial growth factor and endothelin-1 in pathogenesis of retinal vein occlusion

RELATIONSHIP BETWEEN T CELL IMMUNITY PARAMETERS AND SMOOTH-CELL CARCINOMA ANTIGEN (SCCA) CONTENTS IN BLOOD SERUM FROM THE PATIENTS WITH LOCAL DISSEMINATED FORMS OF UTERINE CERVIX CANCER

Uterine cervical cancer is among the main items of modern oncology. Determination of SCCA levels in blood serum of women with locally disseminated forms of uterine cervical cancer has a great significance for estimation the extent of lesions, tumor progression patterns, as well as treatment monitoring. During our study, we have determined that, before starting a specific treatment, all the patients with locally disseminated forms of cervical cancer had high serum levels of SCCA, along with suppressed anti-tumor immunity.Interestingly, high SCCA levels in blood serum proved to correlate with a decrease in anti-tumor immunity factors in those patients who showed a negative dynamics of tumor progression within one year after the therapy was performed. Meanwhile, the patients with positive post-treatment dynamics exhibited a significant decrease of SCCA levels over a year after therapy, as compared with appropriate pre-treatment values, accompanied by increase in anti-tumor immunity markers in these cases