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Background. The problem of gastric cancer remains unresolved throughout the world, while chronic atrophic gastritis (CAG) increases the likelihood of its development by 15 times. In the Russian Federation, the incidence of gastric cancer (GC) is among the highest, with it prevailing among males. One of the leading mechanisms in molecular pathology of membranes is lipid peroxidation (LPO). The severity of oxidative membrane damage depends on concomitant diseases, contributing to emergence and progression of pathological processes and development of cancer. Currently, the problem of LPO is unsolved in biological systems.The aim of this study was to investigate the state of LPO and antioxidant defense system in CAG and GC. Materials and methods. The parameters were studied in 45 patients with CAG and 50 patients with GC. The control group included 50 practically healthy volunteers without gastrointestinal complaints, who did not have changes in the gastric mucosa according to the fibroesophagogastroduodenoscopy (FEGDS) findings.Results. In patients with CAG, an increase in malondialdehyde, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase was found in the blood plasma compared with the control group. In patients with CAG, lipid peroxidation was activated, and the malondialdehyde level increased by 3.5 times relative to normal values. At the same time, the body fought against oxidative stress by increasing the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase. All patients with GC showed pronounced oxidative stress in the blood plasma in the form of a 45-fold increase in malondialdehyde. The activity of the main antioxidant enzyme superoxide dismutase was reduced in GC. Catalase was activated, which indicated pronounced oxidative stress, significant damage to blood vessels, and massive cell death. Glutathione-related enzymes (glutathione S-transferase and glutathione peroxidase) and the antioxidant protein ceruloplasmin were activated, which also indicated significant oxidative stress and severe intoxication in patients with GC.Conclusion. Depending on the stage and type of cancer, an in-depth study of lipid peroxidation and factors of the antioxidant defense system can be used to correct therapy and prevent cancer and can serve as markers of progression and prognosis in gastric cancer.

We studied the effect of neural stem cells (NSC) and mesenchymal stem cells (MSC) from mouse adipose tissue on survival, clonogenic activity, and senescence of NSC after exposure to γ-radiation. It was found that survival and clonogenic activity of NSC irradiated in doses of 1 and 2 Gy was enhanced when irradiated cells were co-cultured with non-irradiated NSC and MSC in permeable Transwell inserts. The proportion of senescent NSC (cells with high β-galactosidase activity) increased with increasing irradiation dose. Co-culturing with non-irradiated NSC in 3 days after irradiation in a dose of 1 Gy led to a decrease in the proportion of senescent cells among irradiated NSC. Factors secreted by NSC and MSC can become the basis for the development of means for prevention and treatment of damage to brain cells resulting from radiation therapy of head and neck cancer.

Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through the nuclear receptors and the insufficiently studied membrane progesterone receptors (mPRs) belonging to the progestin and adiponectin Q receptor (PAQR) family. We have identified two selective ligands of mPRs that activate only this type of progesterone receptors - 19-hydroxypregn-4-en-20-one (LS-01) and 19-hydroxy-5β-pregn-3-en-20-one (LS-02). The goal of this work is to study the effect of these compounds on proliferation and death of human pancreatic adenocarcinoma cells BxPC3 and involvement of the two kinases (p38 MAPK and JNK) in signaling pathways activated by progestins through mPRs. It was shown that progesterone and the compound LS-01 significantly (p0.05) inhibited the BxPC3 cell viability, with JNK serving as a mediator. The identified targets of these two steroids are the genes of the proteins Ki67, cyclin D1, PCNA, and p21. Progesterone and the compound LS-01 significantly (p0.05) stimulate DNA fragmentation, enhancing the cell death. The p38 mitogen-activated protein kinase (MAPK) is a key mediator of this process. The BCL2A1 protein gene was identified as a target of both steroids. The compound LS-02 significantly (p0.05) alters membrane permeability and changes the exposure of phosphatidylserine on the outer membrane leaflet, also enhancing the cell death. This compound acts on these processes by activating both kinases, JNK and p38 MAPK. The compound LS-02 targets the genes encoding the proteins HRK, caspase 9, and DAPK.

Sulfonylureas are widely prescribed all over the world, mainly because of their high effectiveness. At the same time, the heterogeneity of the group is obvious, primarily in relation to the effect of drugs on the risk of developing hypoglycemic events. The review presents the results of new studies, including «Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes» and results of a model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes, confirming the higher efficacy of modified release gliclazide (gliclazide MB) compared to DPP-4, as well as a low risk of hypoglycemic conditions. The results of recent studies, as well as the results of the ADVANCE and ADVANCE-ON studies, suggest that gliclazide MB is safe to use as a second-line drug, especially in patients with chronic kidney disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in highly developed countries. The risk of developing NAFLD and associated complications varies greatly among people of different nationalities and is determined by environmental and genetic factors. Genome-wide studies have revealed strong and reproducible associations between gene variations such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1, and NAFLD. In this article, we consider the influence of genes and environmental factors on the pathophysiological features of NAFLD. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants, will inevitably improve the understanding of the pathogenesis of NAFLD, and will allow the development of a technology for personalized risk in assessing the disease in a patient. The aim of our study was to study the genetic predictors of NAFLD based on literature data with the interpretation of the studies. There is now strong evidence that specific variants of genetic risk have a large effect on NAFLD, and their effect is comparable to that of major metabolic risk factors such as obesity and type 2 diabetes. The increased risk extends to the onset and progression of the entire spectrum of NAFLD manifestations, including overall mortality due to liver disease. Currently, individual genetic variants do not allow the creation of a personalized risk profile; therefore, the most expedient approach today is the development of polygenic risk assessments. The number of genetic loci associated with the prevalence and outcome of NAFLD remains limited. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants and will inevitably improve the understanding of the pathogenesis of NAFLD and will allow the development of a technology for personalized risk in the assessment of the disease.

Aim. To study the content of cytokines in the blood serum of patients with obstructive jaundice of gallstone origin before and after surgical treatment, depending on the development of postoperative complications.Materials and methods. The treatment group consisted of 70 patients with the diagnosis of obstructive jaundice of gallstone origin, verified following a comprehensive clinical and instrumental examination. In 54 patients, the postoperative period was uncomplicated, and in 16 patients, various infectious complications in the postoperative period were revealed. The control group consisted of 125 healthy volunteers. The concentration of six cytokines (interleukin (IL)-2, IL-4, IL-18, IL-10, tumor necrosis factor alpha (TNFα), and interferon gamma (INF γ)) was determined using reagent kits manufactured by Vector-Best LLC (Novosibirsk, Russian Federation) by enzyme-linked immunosorbent assay on the Thermo Scientific analyzer (BioMerieux, France).Results. We identified significantly high concentrations of proinflammatory cytokines in the blood serum of patients with obstructive jaundice of gallstone origin upon admission, compared with the data obtained in the study of blood serum in the control group and in patients with obstructive jaundice after surgery. In the postoperative period in patients with obstructive jaundice without complications, the proinflammatory cytokines are significantly reduced and IL-4 is increased, whereas with the development of infectious complications, the level of proinflammatory cytokines is significantly elevated.Conclusion. In the pathogenesis of obstructive jaundice, a local inflammatory process plays an essential role. This is confirmed by statistically significant changes in the studied cytokines. The established increase in the concentration of IL-4, which has anti-inflammatory activity, indicates its importance in the mechanisms underlying the absence of infectious complications in the postoperative period of obstructive jaundice of gallstone origin. The revealed increase in the levels of IL-18, TNFα, and INFγ in the blood serum of patients suggests their role in the pathogenesis of infectious complications in the postoperative period of obstructive jaundice of gallstone origin.

Aim. A study of monocyte chemiluminescent activity at variant stages of gastric cancer.Materials and methods. The study enrolled 90 gastric cancer patients and 70 healthy donors. Spontaneous and induced chemiluminescence in monocytes was assessed for 90 min with a “BLM 3607” 36-channel chemiluminescence analyser (Russia). Opsonized zymosan-induced chemiluminescence enhancement was measured as a ratio of the areas under the induced vs. spontaneous chemiluminescence curves, the activation index. Statistical significance was estimated with the Mann—Whitney criterion (p < 0.05).Results. The maximal spontaneous monocyte chemiluminescence intensity significantly decreased in stage IV gastric cancer patients compared to the control cohort (p = 0.035). Time to maximum in spontaneous chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.043). The areas under a curve in spontaneous and induced monocyte chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.037). The activation index was higher in all gastric cancer cases compared to control (p = 0.001).Conclusion. All patients with gastric adenocarcinoma, irrespective of the stage, revealed changes in the monocyte chemiluminescence activity, i.e. a longer time to maximum in spontaneous chemiluminescence and larger area under the curve of spontaneous and induced chemiluminescence, the activation index. Maximal monocyte spontaneous chemiluminescence intensity diminished in stage IV gastric cancer compared to the control cohort. Immune activity reflected in monocyte chemiluminescence correlates with the stage of gastric adenocarcinoma.

The production of new effective hemostatic materials based on a polymer composition of modified chitosan with a three-dimensional cross-linked structure as a polymer matrix and calcium ions coordinated to it is addressed. The optimum concentration of calcium ions in the chitosan-based composition was established as 10 – 20 mM and ensured an effective in vitro blood coagulation time of 40 sec. Compositions of chitosan succinate and chloride in addition to chitosan in solutions with nicotinic acid were shown to have effective hemostatic activity. Statistical differences in the effects of various calcium salts on the blood coagulation time were not found. In vivo tests showed that a chitosan-based composition was effective for stopping bleeding of any degree of severity, both with external and internal injuries to tissues.

The aim of the work is to increase the effectiveness of physical therapy of gross motor functions impairments in children with spastic cerebral palsy by using a therapeutic exercises program with partial body weight supporting and motivated walking on the device for the rehabilitation of people with impaired functions of the musculoskeletal system. The study included 30 children 6 to 11 years old with a spastic form of cerebral palsy. All patients were divided into 2 groups: in group I, in addition to the standard complex of physical therapy, walking according to the dynamic method was prescribed, in group II – according to the static method with partial body weight supporting. The duration of the program was 6 weeks. The survey was carried out before the start, at 2, 4 and 6 weeks of therapy. We studied the spatiotemporal characteristics of walking and activity of daily living indicators. The use of the developed program with the rehabilitation device positively influenced the spatiotemporal indicators of walking in both groups. The stride length, walking speed and the length of the covered distance increased statistically significantly. A significant increase in the volume of performed activities of daily living in the I group was found. At the same time, an increase in this indicator was also observed in group II, but it did not reach statistical significance. The use of the developed program of therapeutic exercises, including walking with motivated movement and partial body weight supporting on the developed rehabilitation device positively influenced the static and dynamic characteristics of walking, which improved the performance of activities important for children with cerebral palsy, especially walking and running. The optimal time for increasing the stride length is a 4-week program, for the development of general endurance and speed – a 6-week program of therapeutic training.

Chronic atrophic gastritis and gastric cancer represent distinct steps of one pathogenic process. The risk of developing cancer of the stomach is directly proportional to the degree of atrophic changes simultaneously detected in antral segment and in the body of the stomach. The role of immune system in transformation of precancerous diseases into cancer is beyond doubt. During development of the malignant disease, the changes in lipid peroxidation systems – antioxidant defense become significant and contribute to the progression of the tumor and the development of metastases. A simultaneous study of lipid peroxidation and antioxidant defense indices along with phagocytic activity will allow us to evaluate relative contribution of these processes to development of chronic atrophic gastritis and gastric cancer. Purpose of the present study was to assess correlations between the lipid peroxidation indices, i.e. antioxidant protection, and chemiluminescent activity of neutrophilic granulocytes and monocytes in chronic atrophic gastritis and gastric cancer. Forty patients with chronic gastritis, 22 patients with chronic atrophic gastritis and 40 patients with gastric cancer were examined. The control group consisted of 50 practically healthy age-matched volunteers. Evaluation of spontaneous and induced production of reactive oxygen species by neutrophils and monocytes was carried out by chemiluminescent analysis. The parameters of lipid peroxidation/ antioxidant protection were determined by spectrophotometric methods. Statistical data processing was carried out using the Statistica v. 8.0 program (StatSoft Inc., USA). The normal distribution of indices was tested using the Kolmogorov–Smirnov method (adjusted by Lillefors). Quantitative indicators, given the normal distribution, were described using the median (Me) and interquartile scatter (Q0.25-Q0.75). To study statistical significance of differences between quantitative characteristics, the Mann–Whitney test was used. To study strength of relationships of these indicators, the Pearson rank correlation coefficient (r) was calculated. The critical significance level (p) when testing statistical hypotheses was taken equal to 0.05. Correlation analysis showed that the weight of positive correlations increases in patients with chronic atrophic gastritis, and it decreases in patients with gastric cancer, the strength of the correlation dependence and new relationships appear between chemiluminescent activity of neutrophils and monocytes in a spontaneous and induced state, and the amounts of malonic dialdehyde, enzyme activities of superoxide dismutase and catalase. In chronic atrophic gastritis and gastric cancer we have established the features of correlation patterns between lipid peroxidation/antioxidant protection indices, and activity of neutrophils and monocytes.

Despite the fact that effects of thyroid hormones were noticed back in the 80s, the underlying molecular mechanisms have not yet been elucidated. Current review summarizes years of investigations upon molecular targets for the action of thyroid hormones, leading to changes in the electrical and mechanical activity of the heart; changes in hemodynamics, affecting the functioning of the heart muscle, are also touched.

The purpose of the study: is to establish the characteristics of the development of endogenous intoxication during experimental obstruction of the urinary tract. Materials and methods: to achieve this goal, one control and three experimental groups of animals were formed, in which blood was taken from the marginal ear vein on the 3rd, 7th, 14th and 21st day of the experiment. The following parameters were determined in blood serum: urea, creatinine, total protein and albumin. The level of endogenous intoxication was assessed by the indicators of medium-mass molecules, circulating immune complexes and malon dialdehyde. Results: statistical analysis of blood biochemical parameters and endogenous intoxication markers confirm the link between modern biomarkers of renal injury and morphological changes in the tissues of obstructive and compensatory organs. Conclusion: our findings point to the overstress adaptation mechanisms, the development of oxidative stress and exhibit a high level of endogenous intoxication, resulting in structural and metabolic changes in the affected and in the contralateral kidney.

We analyzed the expression of molecular targets of natriuretic action of prolactin in different layers of the kidney in the rat model of cholestasis of pregnancy. Sodium bicarbonate cotransporter NBCe1 was most sensitive to the conditions of cholestasis and cholestasis of pregnancy: the expression NBCe1 mRNA and protein in the renal outer medulla decreased in comparison with the normal. All forms of cholestasis affected the mRNA expression of sodium-potassium chloride co-transporter NCC, α-subunit of the ENaCα epithelial sodium channel, and Nedd4-2 ubiquitin ligase in different layers of the kidney. The obtained data suggest that prolactin provides fine tuning of various sodium transporters in different parts of the nephron under pathological conditions.

The article discusses the current principles of diagnostic radiology in theevaluation of suspected and verified cervical cancer (CC). Possibilities of magnetic resonance imaging in the primary diagnosis of the disease and effect evaluation of neoadjuvant treatment are described.Conditions and optimal MR-technique, as well asprinciples of data interpretation are discussed. The main prognostic factors for CC are consideredand, also, a brief review of treatment methods for various diseases stages is given.

Objective: comparative evaluation of treatment methods for neoadjuvant intra-arterial chemotherapy and chemoembolization by drug-saturated microspheres followed by surgical treatment in II–IVa stages cervical cancer.Materials and methods. This study presents the results of complex treatment in 209 patients (average age – 40.57 ± 8 years) with II– IVa stages cervical cancer and 384 endovascular interventions as the first stage of complex treatment in the period from 2010 to 2016. The scheme neoadjuvant intra-arterial chemotherapy was carboplatin (AUC6 intra-arterial) + irinotecan (200 mg/m2 intravenously on day 1) every 21 days. Radical surgical treatment was performed basically after 2 cycles of chemotherapy. Patients who did not respond sufficiently to neoadjuvant intra-arterial chemotherapy underwent a radical course of chemoradiation therapy according to the standard scheme.Results. The overall response to neoadjuvant intra-arterial chemotherapy was 84.8 % and 79 % of patients in groups of chemoinfusion and trans-arterial chemoembolization, respectively (p >0.05). Operability was higher in group of chemoinfusion (69 % versus 46.4 %) (p Conclusions. Neoadjuvant intra-arterial chemoinfusion and chemoembolization using irinotecan + carboplatin scheme are relatively safe treatment methods with acceptable toxicity and have a high cytotoxic effect. Patients in chemoinfusion group have a better prognosis compared with patients in chemoembolization group. Selective chemoembolization with subsequent surgical treatment or radiation therapy may be the treatment of choice for stage II cervical cancer complicated by bleeding.

Progesterone (P4) and its analogues regulate various reproductive processes, such as ovulation, implantation, pregnancy maintenance and delivery. In these processes, an important role is played by the immune cells recruited to the female reproductive organs and tissues, where they are exposed to the action of P4. Progestins regulate cellular processes, acting through nuclear steroid receptors (nSRs), membrane P4 receptors (mPRs), and through the sensors. It remains unclear, what type of receptors is used by P4 and its derivatives to exert their effect on the immune cells and how similar their effects are in different types of these cells. We have previously synthesized new progesterone derivatives, among which two selective mPRs ligands, not interacting with nSRs were identified. The objective of this study was to examine the effects of P4 and new selective mPRs ligands on the expression of pro- and anti-inflammatory cytokines in activated human peripheral blood mononuclear cells (PBMCs), THP-1 monocyte cells, and Jurkat T cells. It was demonstrated that the action of P4 and selective ligands was unidirectional, but in different types of the immune cells, their effects were different, and sometimes even opposite. In PBMCs, exposure to these steroids resulted in the increase of mRNA and secreted protein levels of IL-1β, TNFα, and IL-6 cytokines, as well as in the increase of INFγ mRNA level, decrease of IL-2 mRNA level, increase of TGFβ mRNA level, and decrease of IL-4 mRNA and IL-10 secreted protein levels. In monocytes, similarly to PBMCs, expression of IL-1β and TNFα mRNA was increased, but expression of IL-10 was also increased, and the TGFβ expression statistically significantly remained the same. In Jurkat T cells, expression of IL-2 and TNFα mRNA decreased, while expression of IL-10 increased, and expression of TGFβ did not change. Thus, progestins act on the immune cells through mPRs and have both pro- and anti-inflammatory effects, depending on the phenotypes of these cells. The data obtained are important for understanding the complexity of the immune system regulation by progestins, which depends on the type of the immune cells and individual characteristics of the immune system.

Objective:to assess the efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in patients with FIGO stage IB2–IIB locally advanced cervical cancer.Materials and methods.We evaluated the efficacy and toxicity of 3 cycles of intravenous dose-intensive neoadjuvant chemotherapy with either AP regimen (cisplatin 75 mg/m2 and doxorubicin 35 mg/m2) or TP regimen (cisplatin 60 mg/m2 and paclitaxel 60 mg/m2).Results.The study included 105 patients (75 in the AP group and 30 in the TP group) aged between 27 and 63 years (mean age 44 years) with primary verified cervical cancer (T1–2B0–2Nx–0M0). Surgery was performed in 66 patients (88 %) from the AP group and 24 patients (80 %) from the TP group. Six patients (8 %) receiving AP regimen and 1 patient (3.3 %) receiving TP regimen developed disease progression. Four women (2.8 %) from the AP group developed relapses, whereas none of the patients from the TP group had relapses. Dose-intensive chemotherapy did not cause any significant complications at both chemotherapeutic and surgical stages. Our findings suggest that dose-intensive neoadjuvant chemotherapy is an effective method with an objective response rate of 84 % (63 cases) and 56.7 % (17 cases) in groups AP and TP respectively. Fifty-nine patients (78.7 %) receiving AP regimen had pathological response; of them, 7 participants (9.4 %) demonstrated pathological complete response (ypCR). In the TP group, 19 patients (63.3 %) had pathological response and 4 patients (13.4 %) had pathological complete response. Median follow-up time was 16.7 months (range: 3–29 months) in the AP group and 9.1 months (range: 2.8–12.7 months) in the TP group.Conclusion.Dose-intensive neoadjuvant chemotherapy can be considered as an alternative to standard treatment of locally advanced cervical cancer; however, further studies are needed due to the small sample size in this study.

Colorectal cancer is one of the most common malignant diseases in Russia worldwide making up 5-6% of all human malignant tumors. Neutrophilic granulocytes are actively involved in development of antitumor response. A key role in tumor regression is assigned to active forms of oxygen produced by neutrophils. In connection with these pre-requisites, our goal was to study functional characteristics of spontaneous and induced chemiluminescent activity of neutrophil granulocytes in patients with rectal cancer before starting pathogenetic therapy and in subsequent dynamics. The paper presents some laboratory results, i.e., functional indices of neutrophilic granulocytes’ activity in 36 patients with rectal cancer being at different stages of oncological process. The control group consisted of 112 practically healthy volunteers, comparable in sex and age to the group of patients under study. To perform the study venous blood was taken from patients to vacuum test tubes with lithium heparin in the morning time before surgical treatment, and on day 7 after the surgical intervention. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes in a 36-channel “CL 3606” chemiluminescence analyzer (Russia). The following characteristics were determined: time of the curve transition to maximal chemiluminescence intensity (Tmax), maximal value of chemiluminescence intensity (Imax), integral area under the chemiluminescence curve (S). Luminol was used as the chemiluminescence enhancer. Opsonized zymosan was used to induce the respiratory explosion. Chemiluminescence amplification induced by opsonized zymosan was evaluated by the ratio of induced-tospontaneous chemiluminescence (Sind/spont) designated as an activation index.Analysis of chemiluminescence activity in neutrophilic granulocytes showed a significant increase in spontaneous chemiluminescence activity at the stages III and IV of the disease. The production of active oxygen forms induced in neutrophilic granulocytes by opsonized zymosan increased in all the study groups, relative to control parameters. The area under the curves of spontaneous and induced chemiluminescence in patients with colorectal cancer at all stages of the oncological process is less, as compared to the control group, which, despite high indices of maximal chemiluminescence activity, may indicate insufficient total production of reactive oxygen species. The time-to-peak values of the chemiluminescence curves in patients with rectal cancer at all stages of the disease did not show statistically significant differences from the control group.

Mechanical jaundice (MJ) of malignant genesis is a clinical syndrome caused by obturation of bile ducts due to malignant tumor growth. It is characterized by specific pigmentation of skin, mucous membranes and sclerae due to increased accumulation of bilirubin in blood serum and other fluids and tissues of the organism. Various immune disorders are detected in patients with mechanical jaundice. Immune reactivity in mechanical jaundice is affected by toxic, infectious, or tumor factors. In connection with these findings, the aim of our study was to measure levels of some pro-inflammatory (IL-2, IL-18, TNFα, IFNγ) and antiinflammatory (IL-4 IL-10) cytokines in patients with malignant disease, depending on serum bilirubin levels. The study included 50 patients with MJ by malignant origin. A control group consisted of 125 practically healthy volunteers comparable with the study group by sex and age. Blood serum cytokine contents in patients and controls was determined by enzyme immunoassay using reagent kits produced by ZAO Vector-Best. Statistical evaluation of data was carried out by means of Statistica for Windows 8.0 and Microsoft Excel software. The levels of IL-2, TNFα, IFNγ and IL-18 were increased before surgery in the patients with mechanical jaundice of malignant genesis, while IL-4 and IL-10 values were reduced in comparison with healthy controls. Altered cytokine regulation in the MJ group manifests as increase in proinflammatory and immunostimulatory cytokine levels, along with decrease in anti-inflammatory cytokine amounts. Predominant feature of immune response may be regarded as prevalence of Th1-immune response when taking into account cytokine levels in blood serum of patients with MJ of malignant genesis. The features of cytokine regulation of patients with malignant MJ depend on the bilirubin content in blood serum. These changes were most frequent in patients with bilirubin level exceeding 60 μmol/L. In general, the quantitative indices of cytokines exhibited unidirectional changes in the groups of MJ patients with different bilirubin levels, except of IL-10. This parameter showed almost 6-fold increase in MJ patients with bilirubin level < 60 μmol/L against control group, and approximately 40 times with respect to the remaining 2 groups. This biological effect may occur due to malignant etiology of the MJ.

In recent years, there has been an increasing interest in myostatin, a hormone that inhibits the growth and differentiation of muscle tissue. This interest is associated with an increase in the amount of data on the spectrum of the myostatin functioning. Myostatin, which has been known since 1997, belongs to the family of transforming growth factor β (TGF-β) and is a paracrine factor of skeletal muscle myocytes. It turned out that myostatin also affects the satellite cells and muscle fibroblasts, and its functions are not only to limit growth, but also to remodel skeletal muscles, which is necessary for muscle adaptation to physical training. Recent studies show that myostatin can play a significant role in musculoskeletal and cardiac cachexias in various pathologies, including cancer. It has been found that myostatin can be produced not only by skeletal muscle cells, but also by adipocytes and cardiomyocytes. It has been shown that, in cardiac pathology, the level of myostatin production increases in cardiac tissue. It is suggested that an increase in the myostatin production in the heart is necessary to prevent myocardial hypertrophy, which develops in some cardiac diseases. In this review, we examined the myostatin functions, as well as aspects of myostatin gene expression, mechanisms of its biosynthesis, its effect on various intracellular targets and transcription factors, and the regulation of its production. The importance of myostatin functions, as well as its involvement in pathological processes, allows us to consider this hormone as a promising target in therapeutic studies.

Insulin glargine, synthesized using recombinant DNA technology in a concentration of 100 U/ml, was the first once-daily longacting insulin analogue introduced into clinical practice in 2000. Glargin has a well-established record of efficacy and safety and is the most widely used insulin worldwide. In February 2015, the drug lost its US patent protection, which opened the door for biosimilar competitors.

Aim. To study the oxygen transport function in red blood cells and energy balance in patients suffering from epistaxis of various progress severities. In case of epistaxis a single blood loss is insignificant, yet in case of recurrent epistaxis there is a threat of a tissue hypoxia development. However no indicator blood values demanding transfusion therapy exist these days. This is a study of the blood oxygen transport function and energy balance in the red blood cells in those suffering from single epistaxis, recurrent moderate epistaxis and recurrent severe epistaxis. Materials and methods. In patients’ red blood cells a contents of 2.3-diphosphoglyceric acid (2.3-DFG) and hemoglobin oxygen affinity (Р50) were estimated; energy balance was assessed by the activity of glucose-6-phosphate-dehydrogenase (G-6-FDG), lactate-dehydrogenase (LDG), as well as by the lactate and pyruvate contents in the red blood cells and plasma. Tissue hypoxia severity was assessed by the lactate/pyruvate ratio in blood plasma. Results. It has been determined that in case of single epistaxis the studied parameters do not differ from normal ranges. In case of recurrent epistaxis the level of hemoglobin and P50 goes down, plasma LDG activity goes up, the pyruvate content goes down, while plasma lactate retains within the normal ranges. Conclusion. The stated changes in the carbohydrate metabolism in the red blood cells and blood plasma of patients suffering from severe recurrent epistaxis suggest a breakdown of compensatory mechanisms, which manifests itself in the reduced cell energy reserve and disturbed red blood cell membranes. The obtained data testify that the severity of the state of patients suffering from epistaxis is not only defined by a quantitative loss of red blood cells and hemoglobin, but also by the adaptive capacities of the body, which determine its resistance to hypoxia. The guide link in the pathogenesis of disturbed gas transport function of blood in patients suffering from epistaxis is metabolic acidosis developing as a consequence of tissue hypoxia.

Chronic gastritis is the most common disease of gastro-intestinal tract. Precancerous potential is among most important epidemiological features of chronic gastritis. Immune system plays a distinct role in transformation from precancerous state to malignancy. In this context, the aim of our work was a study of spontaneous and induced chemiluminescence activity of neutrophilic granulocytes in patients with chronic superficial gastritis, chronic atrophic gastritis and gastric cancer. The work presents results of comprehensive laboratory examination of patients with chronic gastritis (CG) (a total of 85 persons. 25 patients with chronic atrophic gastritis (CAG), and 50 patients with gastric cancer (GC) at the age of 19 to 70 years were enrolled. Control group included 115 healthy donors without gastrointestinal complaints at the age of 19 to 67 years. The study was performed with venous blood samples taken from cubital vein into Vacutainer tubes with sodium heparin (5 U/mL) prior to starting any pathogenic treatment. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes at a 36-channel “CL 3606” chemiluminescence analyzer (Russia). In our study, patients with gastric cancer showed clear unidirectional changes in chemiluminescent activity of neutrophilic granulocytes (NG). When measuring spontaneous and induced NG chemiluminescence, we diagnosed a decreased phagocytic activity characterized by prolonged time-to-peak and area under the curve for spontaneous and induced CL, thus presuming longer activation time required in cases of reduced phagocytic function. The NG activity in patients with chronic gastritis is not impaired, but, similar changes of time-to-peak and area under were detected. Chemiluminescent activity of NG is increased in the group of CAG patients, and, considering similar changes in activation time and area under the curve, NG also produce greater amount of reactive oxygen species. Thus, for all H.pylori-associated diseases, the blood NG take longer time to activate, whereas their functional activity is not disturbed in CG, enhanced in CAG patients, and reduced in gastric cancer.

The review focuses on the key sodium transporters involved in maintaining water–salt balance in the kidney. The topography of sodium transporters is discussed. Specifics of the hormone-dependent regulation, including phosphorylation, traffic, and expression, are considered for particular transporters. Special attention is paid to direct intracellular regulators of the transporter function. The role that dopamine plays as a natriuretic factor in modulating the function of various transporters is described.

Endometrial cancer (EC) is the third most common cancer. It comprises almost 10 % of all malignant tumors in women. Peak morbidity is observed at advanced age (62–64 years) and is associated with excess weight. At the time of diagnosis more than 70 % of patients have stage I disease and most of them have a concomitant pathology: diabetes, thrombosis, or hypertension. These patients require a low-trauma panhysterectomy which can be performed laparoscopically or laparotomically. Due to improvement of technological equipment in hospitals and development of surgical and anesthetic techniques, frequency of laparoscopic surgeries at large medical institutions is increasing. Comparative long-term results of oncological treatment allow to pose a problem of comfort in the postoperative period as a reason to prioritize laparoscopic access. In order to include the surgery into standard practice, it is beneficial to calculate economic costs for each type of surgical access. Objective. Evaluation of effective costs of panhysterectomy performed laparoscopically and laparotomically for treatment of early stage endometrial cancer. Materials and methods. We performed a retrospective analysis of medical histories of 170 patients with stage I EC who underwent panhysterectomy at the N. N. Petrov Research Institute of Oncology in 2010–2017. Calculations of direct medical costs took into account costs of surgery, drug therapy, treatment of complications, and in-patient care. Indirect costs were based on statistical data on salaries in 2016 and employment in the Russian Federation. Results. For laparoscopic panhysterectomy we observed significant decrease in intraoperative blood loss (82 %), number of drugs, rate of early postoperative complications (mostly associated with postoperative wound healing), and duration of postoperative rehabilitation characterized by short hospital stay and quick return to work. Cost component of the above-mentioned trends amounts to decrease in cost value of 4,000–5,000 rubles for every patient. Conclusions. In long-term perspective, initial investments into high-tech minimally invasive techniques lead to economic benefits due to decrease in costs of in-patient care and treatment of postoperative complications and quick rehabilitation. At the same time, at early stages of EC laparoscopic surgeries don’t affect oncological prognosis for these patients.

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

We studied possible involvement of prolactin in the regulation of bicarbonate biodynamics using female rat model of cholestasis of pregnancy induced by transplantation of the donor pituitary under the renal capsule of a recipient (hyperprolactinemia) and bile duct ligation (cholestasis). The concentration of bicarbonates in the bile and blood, their excretion, clearance, and reabsorption, as well as glomerular filtration rate and excretion of sodium ions were assessed. It was found that the main effect of prolactin was directed to the kidney-regulated pool of bicarbonates and consisted in stimulation of their clearance and inhibition of reabsorption, which led to a decrease in bicarbonate blood concentration. Parallel influence of prolactin on the clearance of bicarbonates and sodium ions was observed.

The search of selective agonists and antagonists of membrane progesterone receptors (mPRs) is a starting point for the study of progesterone signal transduction mechanisms mediated by mPRs, distinct from nuclear receptors. According to preliminary data, the ligand affinity for mPRs differs significantly from that for classical nuclear progesterone receptors (nPRs), which might indicate structural differences in the ligand-binding pocket of these proteins. In the present work, we analyzed the affinity of several progesterone derivatives for mPRs of human pancreatic adenocarcinoma BxPC3 cell line that is characterized by a high level of mPR mRNA expression and by the absence of expression of nPR mRNA. The values were compared with the affinity of these compounds for nPRs. All tested compounds showed almost no affinity for nPRs, whereas their selectivity towards mPRs was different. Derivatives with an additional 19-hydroxyl group and removed 3-keto group had the highest selectivity for mPRs. These results suggest these compounds as the most selective progesterone analogs for studying the mechanisms of progestin action via mPRs.

Cholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstrated: (i) mRNA expression of both PrlR isoforms in the kidney depended on the physiological conditions and prolactin levels; (ii) expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy; (iii) in the case of long PrlR isoform predomination, expression of mRNAs for the prolactin signaling inhibitors SOCS3 and PIAS3 was upregulated (the genes of these regulators contain STAT-responsive elements in their promoters); (iv) expression of the mRNA for galactose-1-phosphate uridyltransferase (GALT), a molecular target of the PrlR short isoform, was decreased in the kidney outer medulla.

Aim. To study changes in the indices of prooxidant and antioxidant systems in plasma in men with atrophic gastritis and gastric cancer. Materials and methods. The study included 60 healthy men, 42 patients with atrophic gastritis and 50 men, nicardipine patients with gastric cancer stage II according to TNM. All patients underwent serological diagnosis of diffuse atrophic gastritis (definition of pepsinogens and gastrin-17) and Helicobacter pylori infection. The diagnosis of "atrophic gastritis" was verified by morphological examination of biopsy specimens obtained during fibroesophagogastroduodenoscopy. Diagnosis of gastric cancer was carried out in the Krasnoyarsk regional oncologic dispensary on the basis of a comprehensive instrumental and morphological examination. All patients spectrophotometric methods in plasma was determined the content of diene conjugates (DC), malonic dialdehyde (MDA), glutathione-S-transferase (GST), glutathione peroxidase (GPO), superoxide dismutase (SOD) and catalase. Results. The concentration of SOD, GST, GPO and catalase had no significant differences in patients with atrophic gastritis and gastric cancer and prevailed in comparison with healthy persons. Patients with cancer of the stomach content in the blood plasma DK 2.7 times and MDA at 35.2 times higher than healthy individuals, indicating severe oxidative stress in patients with cancer. In patients with atrophic gastritis was observed similar but less pronounced pattern. Conclusion. The results indicate the presence of oxidative stress in men with atrophic gastritis and gastric cancer.

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

The status of patients with nose bleedings (NB) depends not only on the volume of blood loss, but also on the degree of compensation for hypoxia accompanying hemorrhage. Aim . The main aim of our research was to study the antioxidant properties of blood serum and the intensity of LPO processes in erythrocyte membranes of patients with epistaxis of varying severity. Materials and methods . 82 patients with nose bleeding of varying severity were examined. The antioxidant activity of the blood serum of patients was studied by the chemiluminescence method induced by divalent iron ions. The processes of lipid peroxidation were studied by evaluating the activity of antioxidant defense enzymes – superoxide dismutase (SOD) and total peroxidase activity in blood erythrocytes, as well as the content of the final product of LPO-malonic dialdehyde (MDA) in erythrocytes. Results. It has been established that the potential of antioxidantprotection of serum and formed elements of blood is one of the most important links in the pathogenesis of NB. Conclusion. High capacity of antioxidant protection can significantly reduce the risk of irreversible changes in erythrocytes and the development of clinical signs of deep tissue hypoxia in patients with epistaxis.

About 50-85% of patients suffer from stump and phantom pain after amputations. These chronic pain conditions are often debilitating and result in disability, sleep and psychosocial disorders, impairment of day-work and the substantial decline in the quality of life. In some patients pharmaceutical therapy may fail to bring satisfactory pain relief or follows severe adverse events. Operations such as rhizotomy, cordotomy and stump revision are often unsuccessful in treating post-amputation chronic pain. The solitary case reports about the using of minimally invasive technique of pulsed radiofrequency (PRF) for treatment of chronic stump and phantom pain have been published only. Our current clinical observation is about successful using of the PRF spinal ganglions in patient with chronic pharmaceutical-resistant post-amputation stump pain.

To study the effectiveness of enhanced recovery after surgery (ERAS) protocol versus traditional perioperative management in patients with hepatopancreatobiliary tumors undergoing pancreatoduodenectomy.The study included 111 patients who have undergone pancreatoduodenectomy between January 2014 and December 2019. Patients were divided into 2 groups: perioperative ERAS protocol (85 patients) and traditional treatment (26 patients). Postoperative complications, length of hospital-stay and incidence of readmissions were analyzed.Mean length of hospital-stay for ERAS protocol was 13.4±7.6 days, conventional management - 16.5±7.5 days (Enhanced recovery after surgery protocol is safe, reduces the number of postoperative complications, length of hospital-stay and rate of readmissions.Стратегия протокола ускоренного восстановления (ERAS) пациентов, перенесших обширные операции на органах брюшной полости, направлена на снижение количества послеоперационных осложнений, уменьшение срока пребывания в стационаре и количества повторных госпитализаций.Изучить эффективность ERAS по сравнению с традиционным периоперационным ведением у пациентов с опухолями гепатопанкреатобилиарной зоны, перенесших панкреатодуоденальную резекцию.В исследование вошли 111 пациентов, перенесших панкреатодуоденальную резекцию в период с января 2014 г. по декабрь 2019 г. Пациенты разделены на 2 группы: прошедшие периоперационное лечение с использованием ERAS (Средняя продолжительность пребывания в стационаре для пациентов, пролеченных с использованием ERAS, составила 13,4±7,6 дня против 16,5±7,5 дня (Следование требованиям протокола ускоренного восстановления безопасно, приводит к снижению частоты послеоперационных осложнений и продолжительности госпитализации.

A huge variety of phytopathogens (viruses, bacteria, fungi) are potentially able to infect plant tissues and cause diseases. Numerous plant genes control a complex network of defense mechanisms based on both constitutive and inducible processes. The cell wall is a primary barrier the pathogens have to penetrate to start the infection process. However,it is able to block invasion by most non-specific potential pathogens. The cell wall structure may differ in various plant species. It is based on the net of cellulose microfibrils linked by hemicellulose molecules. Pectin and lignin are the other important cell wall constituents. Dozens of proteins inside the cell wall are involved in structural and metabolic processes as well as in signal transduction and regulatory circuits (more information is available in W allProtDB database). Each of these components contributes to resistance to pathogens. At the points of contact with potential pathogens cell wall structural changes and accumulation of metabolites with antimicrobial, antifungal or antiviral activities occur. Some pathogens could produce hydrolytic enzymes able to degrade cellulose and pectin to counteract these non-specific plant resistance mechanisms. In turn, plants developed the inhibitors of pathogen-related enzymes and this “arms race” is an important part of plant evolution and host-pathogen interaction mechanisms. Plants also can evaluate the cell wall state to compensate for imbalances and deficiencies. For instance, mutants with cellulose deficiency may have a higher lignification rate and a stronger stress response. The cell wall is also a source of signal molecules triggering the initiation of response mechanisms. In total, the plan cell wall is a complex dynamic structure able to prevent infection by most potential (non-specific) pathogens and switch on the mechanisms of plant immune response. The reconstruction of gene networks controlling the cell wall structural and functional organization during the growth, and under normal and stressful conditions is vitally important for understanding the basic molecular mechanisms of development and stress resistance. The mechanisms of specific and non- specific plant resistance to various phytopathogens connected to the cell wall structure are reviewed. The roles of the cell wall constituents in pathogen detection and the induction of defense mechanism are discussed

Despite the emergence of new antidiabetic drugs, diabetes type 2 treatment remains a relevant issue. In order to standardize and optimize medical care to patients with diabetes, global and national algorithms for type 2 diabetes treatment were developed. [1, 2] The current algorithms focus on an individual approach, safety and effectiveness of treatment. A balance should be maintained between achieving optimal glycemic control and safety of therapy.

Background : Infectious complications — the leading cause of mortality in patients with multiple myeloma (MM), their appearance is regarded as an adverse prognostic factor in the course of the disease. Objective : The aim of our study was to evaluate the clinical and immunological features of infectious complications in patients with G- immunochemical MM to find the most informative indicators in their forecasting. Methods : A randomized controlled trial was made. All patients were divided into 3 groups for comparison: Group 1 (n =47) — MM patients, G-immunochemical variant with infection, Group 2 (n =54) — MM patients, G-immunochemical option no infectious complications, and Group 3 (n =125) — healthy volunteers. Research material was deoxygenated blood taken on admission of a patient to the hematology department before the pathogenetic treatment. Identification of G-variant was carried by immunofixation and electrophoresis. The immune status was assessed by indirect immunofluorescence. The concentration of IgA, M, E and G, and the levels of IL 2, IL 4, IL 8, TNF α, IFN γ in serum was determined by enzyme immunoassay. The activity of neutrophil granulocytes (NG) was studied by chemiluminescent analysis of spontaneous and induced production of reactive oxygen species. Statistical analysis was performed using the software STATISTICA v. 8.0 (USA). Results : We analyzed data from 101 patients with MM and 125 healthy volunteers. The average age of MM patients was 60.53±6.78 years. The group of healthy volunteers was similar in sex and age to groups of patients with MM. In patients with MM in the presence of infectious complications the researchers detected combined secondary development of T and B cell immunodeficiency, changes in non-specific immunity depended on the stage of the disease, unidirectional irregularities in spontaneous and induced chemiluminescence activity NG in II stage disease and multidirectional irregularities in stage III (p =0.045). Prevalence of the content of proinflammatory cytokines on inflammatory (p

The mechanisms displaying pure and mixed steroid agonist/antagonist activity as well as principles underlying in vivo action of selective steroid receptor modulators dependent on tissue or cell type including interaction with various types of nuclear receptors are analyzed in this work. Mechanisms of in vitro action for mixed agonist/antagonist steroids are discussed depending on: specific features of their interaction with receptor hormone-binding pocket; steroid-dependent allosteric modulation of interaction between hormone-receptor complex and hormone response DNA elements; features of interacting hormone-receptor complex with protein transcriptional coregulators; level and tissue-specific composition of transcriptional coregulators. A novel understanding regarding context-selective modulators replacing the concept of steroid agonists and antagonists is discussed.

A method for the chemical modification of humic acids with benzoyl chloride under the conditions of phase-transfer catalysis was developed. It was demonstrated by potentiometric titration that the reaction of humic acids with benzoyl chloride can occur at both hydroxyl (–OH) and carboxyl (–COOH) groups. The antioxidant activity of the initial humic acids and their chemical modification products in radical-chain oxidation processes in an organic medium was determined by a gas-volumetric method. A decrease in the antioxidant activity of the acylated humic acids in comparison with that of the native forms was found; this can be related to a decrease in the amount of active functional groups (–OH,–NH, and–SH) due to binding with benzoyl chloride.

Reviewed the clinical case of empty extrapleural oleothorax. The data of laboratory study, computed tomography and surgcal tactics are given.

Cytokines are wide-range modifiers of biological reactions. Cytokine regulation provides proliferation, differentiation, cell function, cell-cell and inter-systemic interaction, direction and nature of immune response to invasion of infectious and non-infectious pathogens. There are several distinct groups of cytokines: pro-inflammatory, anti-inflammatory factors, regulators of cellular and humoral immunity etc. A distinct role of cytokines is not excluded for infectious complications accompanying multiple myeloma (MM). Cytokine regulatory effects on immune defense in the organism as a whole, and a balance between proand anti-inflammatory cytokines in blood of MM patients depend on the stage of multiple myeloma progression and possibility of infectious complications. Therefore, the aim of our study was to evaluate proand anti-inflammatory cytokines and cytokine regulation in patients with MM G-immunochemical option. Our study involved 101 patients with MM (IgG-variant), their age ranging between 40 and 76 years. The diagnosis was verified by clinical and laboratory examinations. The G-variant of MM was verified by immunofixation and electrophoresis. The definite diagnosis and disease staging was confirmed by a combination of diagnostic criteria. Heparinized blood samples were taken from the cubital vein in the morning (8 to 9 hours), in fasting state upon admission, prior to the starting a pathogenetic therapy. Dynamic monitoring of patients was carried out over the period of their staying in hospital. All patients were staged according to Durie and Salmon (1975) (stages II, III). At each stage, we discerned two sub-groups: A, without renal disease, B, with renal impairment. The control group consisted of 125 healthy volunteers matched for age and sex with the main group. IL-2, IL-4, IL-8, TNFα, and IFNγ levels in sera of the patients and healthy individuals were determined by enzyme immunoassay kits (JSC “Vector-Best”,Novosibirsk). In the myeloma patients, we have revealed an imbalance between pro-inflammatory (IL-2, IL-8, TNFα, IFNγ), and antiinflammatory cytokines (IL-4), with a predominance of pro-inflammatory factors. This finding does not exclude their potential pathogenetic role in growth and stimulation of tumor progression, and occurrence of infectious complications at any stage of the disease. The disturbances in cytokine regulation in MM patients may manifest as a deviation of cellular immune response by Th-1 way. As seen from our data, TNFα, IL-2 and IL-4 are the most significant cytokines for MM progression.

Using immunohistochemical method with semiquantitative analysis of images, we showed that mrp2 expression in response to cholestasis decreased in hepatocytes and cholangiocytes, and remained unchanged in the kidney structures. A decrease of mrp2 expression in renal tubules leading to a decrease of metabolic intoxication of the kidney was demonstrated in cholestasis of pregnancy model. In bile ducts cells, negative correlations of mrp2 with previously measured levels of prolactin receptors, CFTR, and mrp3 were revealed. In renal structures and in hepatocytes, no correlations were found between the expression of these proteins. We hypothesize that prolactin produces a direct effect on mrp2 expression in bile ducts cells mediated by prolactin receptors in cholangiocytes. The absence of correlations between mrp2 and the above-mentioned proteins in hepatocytes and renal structures is most likely related to prolactin effects on other systemic regulators.

Results of recent studies inform about the decrease in the health level in the young people who have signs of dysplasia of the connective tissue. One of the most frequent manifestations of dysplasia of the connective tissue is the hypermobility of joints (HMJ). HMJ is the amount of debris in one or even deciduous slopes is transformed according to the average statistical norm. Patients with the HMJ frequently have the collapse οn side οf thе heart-ship іn system іn thе support-collar apparatus, muscle hypotony, complains at headache and early fatigue during exercising. In this way, the importance of the development of a physical camp is built up by special features from the first manifestations of DCT for the purpose of establishing the necessary physical support on the job because of the physical culture. The aim of the study. Investigate the features of the physical condition of students with external manifestations of connective tissue dysplasia. Object and methods of research. We conducted a study of 155 female students aged 17-20 years, who were engaged in the main medical department on the program of physical education for medical students. Methods: theoretical analysis of literature sources, questionnaires, anthropometry, determination of clinical signs of HMJ according to the criteria of P. Beighton (P. Beighton, 1983), methods of determining the functional state of the body, assessment of physical health, pedagogical testing, methods of mathematical statistics. Research results and their discussion. The average sum of points according to the criteria of P. Baiton is equal to 4.3±1.2 points, which corresponds to a moderately pronounced HMJ. Female students with normal mobility in the joints were group I (n = 39), with moderate HMJ – group II (n = 67), and with significant HMJ – group III (n = 49). The majority of students of group I (21.4%) and group II (21.9%) were engaged in sports games, and representatives of group III (18.5%) preferred gymnastics and dancing. Complaints of unpleasant sensations during exercise, especially the state of the cardiovascular system, more often occurred in members of group III (p

Представлен литературный обзор по проблеме неалкогольной жировой болезни печени (НАЖБП), включающий данные об эпидемиологии, патогенезе, клинических особенностях, диагностике и лечении при сахарном диабете. Приведены данные о влиянии сахароснижающей терапии на прогрессирование или обратное развитие НАЖБП.