The aim of the research. To identify changes in tryptophan and cytokine metabolism in synovial joint tissue in rheumatoid arthritis. Research materials and methods. The experiments were performed on 40 WISTAR rats. At the beginning of the study, each animal of the experimental groups received an intraperitoneal injection of collagen type 2 solution (Chondrex, Inc., USA) in Freund's incomplete adjuvant. The content of tryptophan, kynurenine, 3-hydroxykinurinine, L-5-hydrotryptophan by HPLC with fluorimetric and spectrophotometric detection, and the concentration of cytokines: IL1b, IL6, IL10, IL17, IL18, TNFa were determined in the tissues of the synovial membrane of the knee joint. They were determined using Rat Inflammation Panel V02 multiplex assay kits (Biolegend, USA) on a Cytomics FC500 flow cytofluorimeter (Beckman Coulter, USA). Statistical analysis was performed using the Jamovi program version 2.3.Results. The concentration of cytokines: IL1b, IL6, IL10, IL17, IL18, TNFa was found to be high during the acute development of rheumatoid arthritis. With experimental rheumatoid arthritis, the content of tryptophan metabolites along the kynurenine pathway increases and the concentration of metabolites along the serotonin pathway decreases. Direct positive correlations of IL1b, IL6, IL10, IL17, IL18, TNFa with the content of tryptophan metabolites along the kynurenine pathway have been established.Conclusions. Tryptophan metabolism and IL1b, IL6, IL10, IL17, IL18, and TNFa content are altered in rheumotoid arthritis.

The search for domestic publications on this publication was conducted in the database on the RSCI website, and foreign ones in the PubMed and Google Scholar databases in the period 2022-2023. Their analysis showed that actively studied approaches to the immunocorrection of sepsis are aimed at changing the content or activity of cytokines, growth factors, the use of immune checkpoint inhibitors, as well as myeloid suppressor cells. When modulating the action of cytokines, a variety of approaches are used, such as changing the affinity of cytokines to their receptors, extending the half-life of cytokines and «fine-tuning» the action of cytokines. For the safe and effective use of bioregulators for immunocorrection in sepsis, additional multicenter studies of their clinical effectiveness are needed, including taking into account the stratification of patients into individual endotypes and the mechanisms of action of bioregulators.

Most patients with critical illness, regardless of the cause, develop activation of innate and adaptive immunity. This is often a critical process leading to organ dysfunction. The aim of the review is to systematize information on monitoring the immune system in critical illness for physicians of different specialties (anesthesiology and intensive care, surgery, general practice, obstetrics and gynecology). The review includes information from 83 recent national and international publications (mostly from 2023), available in the public domain and found by keyword search. We have summarized the current understanding of the relationship between infections and the human immune system, as well as the clinical application of traditional markers of immune status. We provided data on novel promising markers for the assessment of immunity in patients with various diseases. Limitations of the studies reviewed include the need for additional large-scale clinical trials of even the most promising markers, as well as a synthesis of the evidence for their performance. In addition, immune monitoring is likely to increase the cost of patient care, necessitating the development of more affordable research methods. Conclusion. Almost all disorders in critically ill patients are associated with changes in the immune system. Management of patients based on their immune profile requires determination of a personalized strategy for immune modulation, treatment, and prevention of infection. Advanced monitoring of immune system functions will contribute to the personalization of medicine, and the continuous development of biological technologies will allow to improve its methods.

BackgroundInsulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).MethodsWe conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.ResultsA total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1–46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.ConclusionsIn this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.

Трехмесячные результаты вакцинации медработников моност ационара препаратом «Гам-КОВИД-Вак»1 Федеральное государственное образовательное учреждение высшего образования «Читинская государственная медицинская академия» Министерства здравоохранения Российской Федерации

Тhe article is dedicated to providing medical assistance and conducting exercises in road traffic accidents.

Thirty apparently healthy elderly women and 72 women diagnosed with Hypertensive Heart Disease (HHD) participated in the study. The subjects with hypertension were divided into two groups: the first group (HHD-1) included women receiving medication; the second group (HHD-2) included women receiving medication and kinesiotherapy (three or four courses regularly during the past two to three years). In elderly women with a high blood pressure, the total number of lymphocytes and eosinophils was higher than in healthy women. The women with hypertension also had higher values of stroke volume (SV), left ventricular end diastolic volume (LVEDV), cardiac output (CO), left ventricular mass (LVDM), and left ventricular mass index (LVMI). In women with hypertension, the balance of velocity distribution in the arteries and microvasculature was shifted toward the fast interlayer processes. In women who exercised regularly, these changes were much smaller. In both healthy women and women with hypertension, there was an association between the total leukocyte count, individual types of leukocytes, the level of blood pressure, and hemodynamic parameters. The strongest relationships were observed between the number of eosinophils and the blood pressure.

Recent studies demonstrated an important role of the junctional adhesion molecule-A (JAM-A) in the pathogenesis of essential hypertension. Our studies showed higher content of JAM-A in women with essential hypertension. Also hypertensive women have higher levels of very low–density lipoprotein (VLDL), higher atherogenic index and lower concentrations of estrogen, progesterone and prolactin, indicating an increased risk of atherosclerosis and premature aging. By the laser speckle showed that the hemodynamic indices considerably change in essential hypertension. The levels of JAM-A correlate with blood pressure, lipids and hemodynamic indices, both in healthy subjects and in women with essential hypertension. The data demonstrate the importance of JAM-A in the pathogenesis of essential hypertension.

Цель исследования: изучить взаимосвязь между концентрацией «белка молодости» GDF11 в крови и состоянием системы гемостаза у здоровых людей и больных гипертонической болезнью (ГБ). Материалы и методы. Обследовано 102 женщины: 30 относительно здоровых женщин (1 группа); 37 женщин, больных ГБ, находившихся на медикаментозном лечении (2 группа); 35 женщин, больных ГБ, находившихся на медикаментозном лечении и регулярно принимавших курсы кинезитерапии (3 группа). Результаты. При ГБ не обнаружено существенных отклонений в числе тромбоцитов, значениях активированного частичного тромбопластинового времени, протромбиновом и тромбиновом времени, содержании фибриногена, но значительно увеличена скорость образования и размер фибринового сгустка, что свидетельствовало о выраженной гиперкоагуляции. Одновременно у страдающих ГБ отмечены выраженные сдвиги в гемодинамических и осцилляторных индексах, говорящих о расстройствах осевого и пристеночного кровотока. У больных ГБ, которые помимо медикаментозной антигипертензивной терапии систематически принимали курсы кинезитерапии на протяжении 2-3 лет, не только нормализовалось кровяное давление, но и приблизились к норме показатели тромбо- и гемодинамики. Заключение. У женщин, страдающих ГБ и находящихся на медикаментозной терапии, содержание «белка молодости» GDF11 резко снижено. У больных ГБ выявлены многочисленные положительные и отрицательные корреляционные взаимосвязи между уровнем GDF11, системой гемостаза, кровяным давлением и гемодинамическими и осцилляторными индексами, характеризующими состояние осевого и пристеночного кровотока. Aim: to study the relationship between blood level of «youth protein» GDF11 and hemostatic parameters in healthy people and hypertensive patients. Materials and methods. We examined 102 women: 30 relatively healthy women (group 1); 37 women with hypertensive disease (HD) who received antihypertensive therapy (group 2); 35 women with HD who received antihypertensive therapy and regular courses of kinesitherapy (group 3). Results. In hypertensive women there were no significant deviations in platelets number, values of activated partial thromboplastin time, prothrombin and thrombin times, fibrinogen concentration, but the rate of formation and size of fibrin clot were significantly increased that was the evidence of significant hypercoagulation. At the same time in patients with HD significant changes in hemodynamic and oscillatory indices were revealed that illustrated the disorders of axial and parietal blood flow. In patients with GB who received antihypertensive therapy and regular courses of kinesitherapy (over the time of 2-3 years) we found normalization of blood pressure, also thrombodynamic and hemodynamic parameters approached to normal. Conclusion. In women with HD who received antihypertensive therapy blood content of «youth protein» GDF11 was significantly reduced. Numerous positive and negative correlations between the level of GDF11, hemostatic parameters, blood pressure and hemodynamic and oscillatory indices that characterized axial and parietal blood flow were revealed in patients with GB.

Цель исследования - изучение взаимосвязи содержания белков GDF11, GDF15, CCL11, JAM-A и кровяного давления у здоровых женщин и женщин, страдающих гипертонической болезнью. Методика. В исследовании приняло участие 118 женщин. Содержание белков GDF11, GDF15, JAM-A и CCL11 определялось методом иммуноферментного анализа (ИФА). Вычислялись коэффициенты, характеризующие отношение «белка молодости» к «белкам старости» GDF11/GDF15, GDF11/CCL11 и GDF11/JAM-A. Величину систолического (SBP) и диастолического давления (DBP) определяли методом Короткова. Результаты. У женщин, страдающих гипертонической болезнью, значительно снижено содержание «белка молодости» GDF11 и повышена концентрация «белков старости» - GDF15, CCL-11 и адгезивной молекулы JAM-A. Установлены положительные и отрицательные корреляции между отдельными исследуемыми компонентами и уровнем кровяного давления. Показано, что чем выше показатель отношения «белка молодости» GDF11 к «белкам старости» GDF15, CCL-11, JAM-A, тем ниже уровень систолического, диастолического и среднего кровяного давления. Заключение. На основании полученных данных сделано заключение, что соотношения уровней «белка молодости» GDF11 и «белков старости» - GDF15, CCL11 и JAM-A играет в регуляции уровня кровяного давления существенно более важную роль, чем каждая из этих молекул в отдельности. Систематическое использование на протяжении 2-3 лет курсов кинезитерапии приводит к восстановлению нормального соотношения «белков молодости» и «белков старости», что сопровождается нормализацией кровяного давления. The aim of this work was to study the relationship between contents of GDF11, GDF15, CCL11, and JAM-A proteins and blood pressure in healthy women and women with essential hypertension. Methods. The study involved 118 women. Contents of GDF11, GDF15, JAM-A, and CCL11 were measured using the enzyme immunoassay (ELISA). Ratios of the «youth protein» to «aging proteins» (GDF11/GDF15, GDF11/CCL11, and GDF11/JAM-A) were computed. Systolic (SBP) and diastolic (DBP) blood pressure was measured using the Korotkov method. Results. In hypertensive women, the content of the «youth protein», GDF11, was significantly reduced, and concentrations of «aging proteins», GDF15, CCL-11, and the adhesion molecule JAM-A, were increased. Some «youth and aging proteins» were positively or negatively correlated with blood pressure. The greater was the ratio of the «youth protein», GDF11, to «aging proteins», GDF15, CCL-11, and JAM-A, the lower was systolic, diastolic, and mean blood pressure. Therefore, the relationship between the ratio of the «youth protein», GDF11, to «aging proteins», GDF15, CCL11, and JAM-A, plays a substantially greater role in regulation of blood pressure than each of these molecules alone. Conclusion. Systematic use of kinesiotherapeutic courses for 2-3 years restores a normal «youth to aging protein» ratio and improves blood pressure.

Essential hypertension (EG) is an age-associated disease. Often EG of elderly patients haven't good way of treatment. Thus, the search of new target molecules for EG therapy is an actual goal of gerontology and molecular medicine. It was shown, that during EG concentrations of GDF11 «youth protein» decreased in 3,3 times and GDF15, JAM-A/1, CCL11 «aging proteins» increased in 1,4-2,4 times. EG patients have abnormal microcirculation processes. It was shown as decreasing in 1,3 and 1,7 times of hemodynamic HI1 and H1-H3 indexes. EG patients have negative correlation of GDF15 concentration with arterial pressure. EG patients have no correlation of JAM-A/1 concentration with arterial pressure. Normal is positive correlation with GDF15, JAM-A/1 concentration with arterial pressure. GDF15 blood level during EG have positive correlation with HI1-HI3 and negative correlation with NEUR_HI2 and MAYER_HI3 indexes. It can show on pathogenesis mechanisms of endothelial and smooth muscles function of vessels tissues. We suppose, that the regulation of GDF11, GDF15, JAM-A/1, CCL11 «youth and aging proteins» can be target object of EG therapy.

Цель исследования: изучить взаимосвязь между содержанием «белка старости» хемокина CCL11, состоянием системы гемостаза и течением кардиогемодинамических функций у женщин, больных эссенциальной гипертонией. Материалы и методы. В исследовании приняли участие 118 женщин. Контрольную группу составили 30 относительно здоровых женщин. Больные гипертонической болезнью (ГБ) были разделены на 3 группы. В группу 1 (ГБ-1) вошли 16 женщин, у которых ГБ была выявлена впервые, в связи с чем они не принимали гипотензивной терапии. Группа 2 (ГБ-2) состояла из 37 женщин, страдающих артериальной гипертензией (АГ) II стадии. В группу 3 (ГБ-3) вошли 35 женщин, регулярно проходившие на протяжении 2–3 лет по 3–4 полуторамесячных курса кинезитерапии. У женщин были исследованы основные показатели коагулограммы и тромбодинамики, эхокардиограмма и гемодинамические функции. Результаты. У женщин с ГБ (ГБ-1) и особенно с АГ (ГБ-2) содержание ССL11 в крови было повышено, тогда как у больных ГБ-3 его концентрация приближалась к норме. У относительно здоровых женщин установлена положительная взаимосвязь между уровнем CCL11 и тромбиновым временем (ТВ). У больных ГБ-2 выявлены положительные взаимосвязи между концентрацией CCL11 и ТВ и отрицательные — с плотностью образуемого фибринового сгустка. У больных ГБ-3 найдены отрицательные связи между содержанием CCL11 и числом тромбоцитов, ТВ и скоростью образования фибринового сгустка. У больных ГБ-3 обнаружены отрицательные взаимосвязи между концентрацией CCL11, ударным объемом и индексом массы левого желудочка, а также основными гемодинамическими показателями. Аналогичные связи сохранялись в общей группе больных (ГБ-2 + ГБ-3), а также общей группе больных и здоровых. Заключение. Содержание «белка старости» хемокина CCL11 оказывает влияние на состояние гемостатического потенциала, сердечную деятельность и гемодинамические функции как у здоровых, так и у больных эссенциальной гипертонией. Aim: to study the relationship between the content of the «age protein» chemokine CCL11, hemostasis and cardiohemodynamic functions in women with essential hypertension. Materials and methods. We examined 118 women. The control group consisted of 30 relatively healthy women. Patients with essential hypertension (EH) were divided into 3 groups. Group 1 (EH-1) included 16 women who had hypertension for the first time, so they did not take antihypertensive therapy. Group 2 (EH-2) consisted of 37 women with stage II of arterial hypertension (AH). Group 3 (EH-3) consisted of 35 women who regularly passed for 2–3 years for 3–4 of 1.5-month courses of kinesitherapy. The main parameters of coagulogram and thrombodynamics, echocardiogram and hemodynamic functions were studied. Results. Blood CCL11 content was increased in women with EH (EH-1) and especially with AH (EH-2), whereas in patients with EH-3 its concentration approached to normal. Positive relationship between CCL11 level and thrombin time (TT) was found in relatively healthy women. In EH-2 patients positive relationship was revealed between CCL11 concentration and TB and negative relationship between CCL11 concentration and density of the formed fi brin clot. In EH-3 patients negative relationshipsbetween CCL11 content and platelet count, TT and fi brin clot formation rate were found. Only EH-3 patients have negative relationships between CCL11 concentration, stroke volume and left ventricular mass index, as well as with basic hemodynamic parameters. Similar relationships maintained in the total group of patients (EH-2 + EH-3), as well as in total group of patients and healthy persons. Conclusion. Content of the «age protein» chemokine CCL11 aff ects the hemostatic potential, cardiac activity and hemodynamic functions both in healthy persons and in patients with essential hypertension.

Aim. To reveal the role of a “youth protein” GDF11 in regulation of lipid metabolism and cardiovascular system work in essential hypertension (EH) in women taking antihypertension medications and regularly involved in moderate physical exercises (kinesitherapy).Material and methods. In all participants, the level of GDF11 was measured by immune enzyme assay, and levels of lipids; registration was done of blood pressure, echocardiography and circulation condition with a novel sensor of dynamic light scattering (mDLS).Results. In women with AH taking antihypertension medications, the level of GDF11 was lower more than 3 times. In EH patients the deviations found, in a shear flow velocity with significant increase of rapid velocity processes. Correlations found for GDF11 level with the age, blood pressure, condition of the heart work, hemodynamical and oscillatory indexes. In the EH group patients regularly doing exercises (kinesitherapy), the level of GDF11, blood pressure, lipid profile and all parameters of heart work and hemodynamics are close to normal.Conclusion. The “youth protein” CDF11 is a factor of prevention of AH. Kinesitherapy in EH patients normalizes GDF11, lipid profile, and significantly increases the work of cardiovascular system.