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Type 2 diabetes mellitus is characterized by a mild inflammatory reaction in the pancreas, which affects the structure and function of the pancreatic islets: the number of β-cells decreases and the number of α-cells increases. The work examined the features of β-cell differentiation in the development of experimental type 2 diabetes mellitus and while reducing the inflammatory process. Biochemical, histological methods, enzyme-linked immunosorbent assay, immunohistochemical methods were used using primary antibodies to insulin, glucagon, proliferation marker Ki-67 and secondary antibodies labeled with fluorescent dyes. Streptozotocin and nicotinamide were used to model type 2 diabetes mellitus, and the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione was used to reduce the inflammatory response. Previous studies have shown that it changes the macrophage phenotype from proinflammatory M1 to anti-inflammatory M2. In type 2 diabetes mellitus, against the background of a decrease in the number of macrophages with the CD163 marker and the concentration of the cytokine TGF-β1, which have an anti-inflammatory effect, in the pancreatic islets, a decrease in the number of β-cells and their functional activity was observed, while the content of α-cells synthesizing glucagon increased. After administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione, the opposite picture was observed in the pancreatic islets: against the background of an increase in the number of CD163+ macrophages and the content of TGF-β1, the number of β cells increased and the number of α cells decreased-cells. The increase in the number of insulin-synthesizing cells was not accompanied by their mitotic activity. It is likely that a decrease in the number of CD163+ macrophages and the level of the antiinflammatory cytokine TGF-β1 in the islets are factors contributing to changes in the cell microenvironment and, as a consequence, the differentiation of β-cells into α-cells. On the contrary, an increase in the number of CD163+ macrophages and TGF-β1 against the background of administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione presumably promotes reverse differentiation of α-cells into β-cells and restoration of insulin synthesis pancreas. Targeted effects on the microenvironment of cells in the pancreatic islet in type 2 diabetes mellitus may be a new approach to treating the disease.

Mental disorders often accompany autoimmune diseases, for example, since 1949 it has been known about “myxedematous madness”, a psychosis caused by hypothyroidism. The most common cause of hypothyroidism is Hashimoto's autoimmune thyroiditis. It is also known about another neuropsychiatric disorder associated with autoimmune thyroiditis, Hashimoto's encephalopathy. It is a severe dysfunction of the central nervous system, the pathogenesis of which is not associated with hormonal disorders. Cytokines are regulators and participants of inflammation, including autoimmune. Certainly, when we are talking about high concentrations cytokines, we mean systemic inflammation. The minimal or mediocre fluctuations in cytokines within the ranges that are characteristic of healthy status or normergic acute phase response in disease cannot be interpreted from the point of view of binary endocrinological logic. In the CNS, cytokines are able to influence on the neuroendocrine control of systemically regulated functions. It is also important that glial cells (astroglia, microglia) are capable of producing a number of cytokines and can affect neurons and develop behavioral changes. In addition, the ability of a number of cytokines outside the CNS itself to act on vagal afferents and through them to convey information to the CNS, affecting its state and functions, has been proven. It is reasonable to assume that minimal fluctuations in cytokine levels may also affect the state and function of the CNS. The aim of the study was to investigate the levels of cytokines in patients with thyroiditis; in patients with thyroiditis associated with mental disorders; in a group of healthy individuals; and evaluate the effect of cytokine levels on clinical manifestations. In the group of patients with thyroiditis and mental disorders, the levels of CCL20/MIP3α, IL-13, IL-2, IL-27, IL-5 were significantly higher than in other groups. At the same time, no positive correlation was found between the clinical manifestations of mental disorders and the levels of cytokines. A positive correlation was found between the levels of some cytokines and free triiodothyronine, as well as the level of antithyroid antibodies. Mental disorders associated with autoimmune thyroiditis may be associated with changes in the cytokine profile and result from neuroinflammation.

Introduction. The prevalence of andrological diseases among adolescents and young adults resulting in lowered reproductive potential has been noted to progressively increase. At the same time, the number of couples starting to manage reproductive issues after 35–40 years of age highlighting the onset of male androgen deficiency continues to rise. Therefore, the analysis of spermogram as the key element in assessing male reproductive potential is better to conduct at different age periods of man's life.Aim: to compare spermogram parameters in different age groups of patients with reproductive pathology.Materials and Мethods. The analysis of spermograms in adolescents with left-sided grade II–III varicocele aged 17 years and in infertile males aged 22–48 years was performed. Semen analysis was conducted in accordance with the standards of the 5 th edition of the World Health Organization and included the following parameters: semen volume (ml), sperm concentration (million/ml), total sperm count (million), acidity, viscosity, progressive motility, total motility, viability, morphology, detected mucus, leukocytes, amyloid bodies, lecithin grains as well as sperm aggregation and agglutination. The stained preparations were used to assess the morphology of spermatozoa and spermatogenesis cells. According to the spermogram data obtained, the following conclusions were drawn: normozoospermia, oligozoospermia, asthenozoospermia, teratozoospermia. Statistical analysis was performed by using Statistica 10.0 software (StatSoft Inc., USA). The normality distribution was assessed using the χ2 test. Quantitative parameters were presented as arithmetic means and standard deviations (M ± SD). Assessing significance of differences was performed by using the Student's t-test, whereas inter-parameter correlation relations were analyzed by using the linear Pearson's correlation coefficient. A significance level between inter-group parameters was set at p < 0.05.Results. It was found that adolescents with varicocele vs. adult men had significantly decreased ejaculate volume. In particular, the average ejaculate volume in adolescents and adult men was 2.32 ± 1.22 ml and 3.50 ± 1.44 ml, respectively, so that the larger number of young patients were noted to have ejaculate volume below 1.5 ml. Compared to young subjects, aged patients had decreased sperm concentration (35.88 ± 25.74 versus 72.20 ± 49.32 million/ml) and total sperm count (120.58 ± 91.72 versus 173.07 ± 163.92 million). Young patients were found to have significantly superior data in all categories of sperm motility, whereas infertile men were diagnosed with impaired sperm motility. In particular, adolescents were featured with the average number of spermatozoa displaying fast and slow translational movement comprising 17.12 ± 11.04 % and 29.30 ± 12.29 %, respectively, the proportion of progressive motility spermatozoa was 46.20 ± 19.82 %. In contrast, similar parameters in adult men were 5.10 ± 6.36 %, 19.80 ± 9.61 %, and 24.95 ± 11.23 %, respectively. In infertile men prevalence of lacked spermatozoa with rapid forward movement was 46 (46.0 %), in adolescents – 8 (8.6%), whereas rate of immotile spermatozoa in infertile men, on average, accounted for 53.10 ± 14.56 %, in adolescents – 34.40 ± 21.83 %. In addition, adolescents with varicocele had significantly fewer spermatozoa with normal morphology – 14.14 ± 8.06 % (in adult men – 30.08 ± 17.94 %), there were more abundant defects in the sperm head – 58.01 ± 12.43 % (in men – 48.83 ± 18.95 %) and flagella – 17.24 ± 6.31 % (in men – 10.29 ± 6.21 %). The data obtained showed that adolescents were more often diagnosed with normozoospermia – in 49 (52.7 %) cases, in infertile men – in 12 (12.0 %) cases, whereas in aged men asthenozoospermia was detected in 82 (82.0 %) cases, in adolescents – 5 (5.4 %) cases.Conclusion. The abnormalities in the spermogram revealed in adolescents may be associated with unestablished spermatogenesis. Normozoospermia more common in adolescents with varicocele may evidence about preserved reproductive potential. Impaired sperm motility in aged patients seems to be related to the formation of oxidative stress and damage to spermatozoa by reactive oxygen species due to combined age-related changes, cumulation of the negative effects of environmental and lifestyle factors, as well as comorbidities.

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology.

Aim. To compare the number of insulin+ cells in the liver and exocrine part of the pancreas with the type of experimental diabetes, blood glycose and glycated hemoglobin (HbA1с) level and with the number of Pdx1+ cells.Materials and methods. The experiment was carried out on 25 male Wistar rats (weighting (303.0 ± 25.3) g) that were divided into 3 groups: the first group consisted of intact animals, the second had animals with experimental diabetes type 1, and the third with animals with experimental diabetes type 2. Biochemical, immunohistochemical, ELISA methods and statistical analysis were used.Results. Insulin+ and Pdx1+ cells of rats with experimental diabetes were found in the liver and exocrine part of pancreas. The highest number of insulin+ cells in the liver was detected in type 2 diabetes (T2D). A strong positive correlation between the number of insulin+ cells in the liver and level of glycosylated hemoglobin in theblood was revealed in both type 1 and type 2 diabetes.Conclusion. Insulin+ cells are detected in the liver and acinar part of pancreas of both intact rats and rats with experimental diabetes. Group with T2D is characterized by the highest number of insulin+ cells in the livercompared with type 1 diabetes (T1D). The localization of insulin+ cells in the liver changes depending on the type of diabetes. In T2D insulin+ cells are located in all parts of liver acini, meanwhile in animals with T1D such cells are mainly detected in the periportal area. The expression of Pdx1+ in acinar cells of pancreas and liver cells is likely a mechanism for their reprogramming into insulin+ cells in experimental diabetes mellitus.

The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

High occurence of liver diseases (toxic, viral hepatitis, liver failure, cirrhosis) requires urgent search of new methods for management of the hepatobiliary diseases. At the present time, the role of immune mechanisms in pathogenesis of diffuse toxic liver damage is not finally clarified. The model of toxic hepatitis induced by carbon tetrachloride (CCl4) is widely known, but this approach allows us to perform complex evaluation and develop the methods for adequate correction of liver disorders in experimental model, which is not always feasible in clinical setting.To design a model of diffuse toxic liver damage, the CCl4 oil solution was used, having been administered intraperitoneally to experimental animals, at a single dose of 50 mg per 100 g body mass. Aiming for correction of toxic liver damage, the injections of aminophthalhydrazide (APH) to experimental animals were carried out intramuscularly at the dose of 2 mg/kg over the terms of experiment. An evaluation of the role of sinusoidal cells (SC) and cytokine production at the local and systemic level were carried out in the model of toxic liver damage caused by CCl4 and its correction by APH treatment. In the course of developing diffuse toxic liver damage induced by CCl4, the production of proinflammatory cytokines TNFα, IL-1α and IL-18 was enhanced at the local level, whereas an increase in TNFα concentration was observed in blood plasma. Following aminophthalhydrazide (APH) administration, the concentrations of proinflammatory cytokines (TNFα and IL-18) decreased at system level, along with locally decreased levels of IL-6 and IFNγ.Changes in the functional state of immunocompetent cells, which include sinusoidal cells (SC), have a significant impact on the development of pathological processes in the liver. The results of our study presume that, over the early periods of toxic impact upon liver tissue, the number of SCs increases both due to influx of blood monocytes and mature macrophages from the peritoneal cavity that enter the injury site directly via mesothelial layer. The SCs provide phagocytosis of damaged hepatocytes and contribute to resolution of the inflammatory process.Modulation of the macrophage activities by APH contributes to increased amounts of SCs at the early stages, and stabilizes their quantities after 2 weeks of APH injections. Change in the numbers of liver SCs during toxic damage affects the production of cytokines. A direct effect of APH upon the SCs may change the production of regulatory factors and compensate the insufficient rate of recovery processes after the toxic damage.

Juvenile idiopathic arthritis is a chronic inflammatory disease of the joints in children, mainly of autoimmune or auto-inflammatory nature. It is a heterogeneous group, which includes different subtypes of the disease. Different mechanisms may play role in the pathogenesis of distinct subtypes of juvenile arthritis. However, a long-term imbalance of pro- and anti-inflammatory cytokines is important for all subtypes of disease. The aim of the present study was to determine spontaneous and stimulated anti-inflammatory cytokines production by peripheral blood cells from the children with juvenile idiopathic arthritis. Patients of 2 to 17 years old with different subtypes of juvenile idiopathic arthritis (n = 99) and healthy children without signs of autoimmune diseases (control, n = 31) were examined. Spontaneous and phytohemagglutinin-stimulated concentrations of IL-1ra, IL-4, IL-10, TGF-β in supernatants of whole-blood cultures were determined by ELISA. Differences in the spontaneous and mitogen-stimulated secretion of the cytokines in patients with different subtypes of juvenile arthritis have not been revealed. The spontaneous IL-1ra, IL-4 and IL-10 production by blood cells in the common group of patients with juvenile idiopathic arthritis was similar to the controls. The median value of spontaneous TGF-β concentration in the patients was below the detection level, whereas blood cells of healthy children had a higher potential of spontaneous TGF-β production. IL-4 and IL-10 production after incubation of peripheral blood cells with phytohemagglutinin in patients and in the control group did not differ from the controls, while IL-1ra and TGF-β synthesis was significantly lower than in healthy children.The spontaneous and/or stimulated production of IL-1ra, TGF-β by blood cells in children with juvenile idiopathic arthritis reflects the pathogenic significance of these cytokines in disease. Stimulation of cells can reveal a latent deficiency in the synthesis of cytokines, which is not evident when determining its concentration in serum or supernatants of spontaneous whole-blood cultures.

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection.

The current obstetrical protocols and the improved perinatal services have led to a significant decrease in the intrapartum and neonatal mortality; however, the rate of antenatal fetal death remains high. In a search for a mechanism of this abnormality, we conducted a comprehensive morphological study of the placental ultrastructure in women with antenatal fetal death. Aim: to determine the ultrastructural characteristics of the placenta in these women. Materials and methods. We analyzed 60 cases of antenatal fetal death and conducted an electron microscopic study of placental terminal chorionic villi. The placenta samples were fixed in 2.5% glutaraldehyde, then processed in alcohol at increasing concentration and acetone for dehydration, and finally polymerized in araldite resin. Ultrathin sections were obtained using an ultra-microtome and then examined with an electron microscope. Results. In 53 (88.3%) women, antenatal fetal death occurred in the early gestation period and in 7 (11.7%) women – at a period of 38-41 weeks. In the main group, the age of women ranged from 18 years to 42 years, and in the comparison group – from 22 to 37 years. In the main group, 16 (26.6%) women were in the late reproductive period (36 years and older). Among the women with antenatal fetal death, the most common diagnoses were: chronic fetoplacental insufficiency (CFPI) – 23 (39%), fetal development retardation syndrome (FDRS) – 16 (27%), and premature detachment of a normally situated placenta (PDNSP) – 10 (17%). Changes in the syncytiotrophoblast structure were detected in patients of both groups; in these changes, signs of vacuolization and destruction were most common. In women of the main group, sclerotic stroma and infiltration by mononuclears were found, whereas loosening and swelling of the stroma were detected in both groups. Changes in the vascular bed were revealed in 100% of cases with antenatal fetal death and in 40% in comparison group. Conclusion. In antenatal fetal death, the most common causes were: CFPI, FDRS, and PDNSP. In the morphological terms, there were destructive changes in the syncytiotrophoblast, edematous-destructive, sclerotic and necrotic changes in the stromal terminal chorionic villi, vascular changes (hypovascularization, stroma obliteration, stasis and erythrocyte sludging, formation of erythrocyte thrombi in the lumens of blood vessels), dysfunctional changes in endotheliocytes, and inflammatory changes.

A comprehensive comparative evaluation of the ability of L-17 compound (2-morpholino-5- phenyl-1,3,4-thiadiazine) and antioxidant lipoic acid (LA) to correct blood cytokine levels, metabolic disorders and morphological alterations in pancreas in alloxan-induced diabetes was performed for the first time, using an experimental in vivo model. All the tested compounds have been found to correct hyperglycemia and decreased accumulation of glycated blood proteins. The tested L-17 compound belongs to the 1,3,4-thiadiazine series and is able to correct metabolic disorders occurring in alloxan-induced diabetes comparable to activity of LA antioxidant. However, L-17 reduces the cytokine levels to the values of intact animals, that preventing development of systemic inflammatory response which causes damage of target organs in diabetes mellitus.

This review article concerns a challenging problem of HIV infection, immune activation. The processes of immune activation largely determine CD4+T cell depletion, leading to development of AIDS-associated and non-AIDS-related diseases. Immune activation indices are also strong predictors of the clinical outcome. Activation in HIV-infection affects both innate and adaptive immune cells, leads to increased proinflammatory cytokine production and blood coagulation. The reasons for immune activation may include different pathogens (HIV, cytomegalovirus, Epstein–Barr virus, hepatitis C virus), lymphopenia and lymphopenia-induced T lymphocyte homeostatic proliferation, transfer of microbial products from the gut, due to profound CD4+T cell deficiency in lamina propria and altered permeability of intestinal barrier. Other factors that promote the process of immune activation are as follows: T lymphocyte "bystander" activation, increased T cell turnover, and systemic inflammation development. The review covers pathogenic mechanisms HIV-infection associated with immune activation, like as description of different laboratory parameters characterizing its manifestations in HIV-infected patients. Significance and prognostic role of these parameters in assessing efficiency of antiretroviral therapy, development of complications, and adverse outcomes of infection are presented as well.

The aim of our study was to identify phenotypic composition and functional activity of immune cells from umbilical cord blood (UCB) as a function of gestational age. We analyzed 102 UCB samples of babies born at 25-28 weeks, 29-32 weeks, and 33-36 weeks of gestation, and 31 samples of UCB from the full-term infants taken as a comparison group (gestational age of 37 to 41 weeks). Using flow cytometry approach, we determined representation of cells with CD3+-, CD19+/CD3-, CD4+/CD3+, CD8+/CD3+, CD16/56+/CD3-phenotypes, along with expression of activation markers among populations of monocytes and lymphocytes (HLA-DR+/CD14+, CD71+/CD14+, CD25+/CD4+, CD95+/CD3+), as well as adhesion receptors (CD11b+). Contents of cytokine-producing cells (IL-4/CD4, IFNγ/CD4) and serum IFNγ and IL-4 cytokines were also determined. All premature babies with existing leukopenia exhibited an increase in relative numbers of lymphocytes, and diminished ability of the granulocytes to absorb opsonized bacteria. Reduced percentage of HLA-DR+/CD14+ cells, increase in CD3+CD95+ cell population and IFNγ producing cells have been shown in a subgroup of children at a gestational age of 25-28 weeks. Decreased levels of natural killer cells was observed among infants < 32 weeks of gestation. Increased concentration of serum IFNγ, along with reduced levels of IL-4 was determined in children born at 25 to 28 and 33 to 36 weeks. A reduced percentage of CD3+CD11b+ cells were revealed in UCB at 29-32 and 33-36 weeks of gestation. Reduced numbers of CD3+CD95+lymphocytes and increased CD25+ receptor expression on the CD4+ cell population was registered at 33 to 36 weeks of gestation. In summary, the findings suggest some features of immune system, which may be specific to particular gestational age of preterm infants. A number of the parameters under study allow us to presume a development of partial immunological response to potential antigens, thus requiring further research aimed for investigation of functional activity of immunocompetent cells.

The essential link in the pathogenesis of diabetes mellitus and its complications is a non-enzymatic glycosylation of proteins. However, modern endocrinology lacks of clinically effective pharmaceuticals for its correction. The screening of 23 derivatives of 1,3,4-thiadiazine the ability to inhibit the reaction of non-enzymatic glycosylation of proteins in vitro was held, and 11 the most active compounds of them were selected, also the relationship «structure – activity» was investigated. An essential part of the pathogenesis of diabetes mellitus and its complications is non-enzymatic glycosylation of proteins. However, modern endocrinology lacks clinically effective medicines for its correction.

Abstract. The effects of 'Profetal', a drug containing liophylized, dextran-stabilized human alpha-fetoprotein as main active component, were investigated on peripheral donor blood mononuclear leukocytes (ML), with respect to their functional properties and the potential to generate mature dendritic cells (DC).Addition of the drug to cell cultures at optimal doses was shown to cause significant increase in their proliferative capacity and ML blastic transformation levels, and enhanced cytotoxicity towards K562 tumor cells, as well as to induce maturation of antigen-presenting dendritic cells.On the basis of the data obtained, a conclusion is made that 'Profetal' is an active immunomodulatory factor, and it may be applied for generation of cytotoxic lymphocytes and mature DC, aiming to apply them for the biotherapy of oncological and infectious diseases.

Abstract. T-lymphocytes play an important role in elimination of tumor cells, in reactions of a transplant against graft and graft versus host disease, in slow-type hypersensitivity, and other reactions directed for maintenance of homeostasis. Along with CD3, an antigen-specific T-cellular receptor (TCR) is another common marker of T-cells. There are two types of TcR – αβ-TcR and γδ-TcR that differ in ontogenetic and functional properties. γδ-T-cells play a significant role in protection of organism against various types of infections, and determination of their amounts should be an integral part of the analysis of patients’ immune status. To these purposes, a multi-colour analysis shuld be used, applying the following combinations of monoclonal antibodies: CD3/CD4/CD8/CD45 and αβ-TcR/γδ-TcR/CD3/CD45. Multi-colour staining and multi-step gating allow of carrying out multiparametric analysis of peripheral blood with high accuracy and reliability. The proposed approach considerably facilitates interpretation of results obtained, and it allows of judging about immune system functioning in various pathological conditions.

Immunomodulating ability of a bacterial preparation (Immunovak VP-4 vaccine), and a compound of eukariotic origin (profetal), the main active component of human α-fetoprotein were under investigation in present study. Culturing of mononuclear leukocytes with the immunomodulatory factors promotes quantitative increase of the cells that express surface antigens specific for cytotoxic lymphocytes, natural killers and natural killer T-cells. Both bio-active preparations possess an expressed anti-cancer effect in vitro, i.e., they induce activation of killing properties of human peripheral blood mononuclear leukocytes, which is accompanied by acquiring their characteristic phenotype.

Abstract. Examination of immunomodulatory actions and clinical efficiency of myelopidum when included into complex therapy that was carried out in 24 male patients with severe (stage 3) penetrating eye injury in the course of trauma treatment. The levels of C-reactive protein, lactoferrin, interleukin (IL)-1β, IL-6, and activity of complement system were measured in peripheral blood, and concentrations of lactoferrin and IL-8 were determined in tears. An increase in lactoferrin, C-reactive protein, IL-1β, IL-8, and C5 complement component levels was detected during early post-traumatic period, as compared with data from the control group. As compared to effects of steroid and non-steroid anti-inflammatory drugs included into standard therapy, treatment with myelopidum has led to a more favorable clinical course of traumatic process, and resulted into more pronounced anti-inflammatory effect that was manifested by decrease in lactoferrin and C-reactive protein levels, reduction of IL-1β concentration, and C5 complement component activity. (Med. Immunol., 2008, vol. 10, N 2-3, pp 239-244).

Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

Abstract. The lecture presents modern data on systemic inflammation, as well as an original concept of its genesis. This disorder is considered a typical pathological process being fundamental to pathogenesis of the most critical states of different origin. Distinct features of “classical” and systemic inflammation are discussed, whereas the underlying immunological and pathophysiological mechanisms of inflammation are subject to classification. Main constitutive processes, phases of systemic inflammation, and certain variants of their proceeding are characterized as well. A definition of “systemic alteration” has been specified.

Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50); elderly persons 60 yrs old, as well as senior persons (n = 22); persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16); climacteric syndrome (n = 16); autoimmune thyroiditis (n = 29). The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI) II-III stage (n=49); valvular cardiac disease (rheumatism, n = 15); psoriatic arthritis (n = 12); reactive arthritis (n = 17); antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5); systemic lupus erythematosus (n=49); decompensated atherosclerosis of femoral artery (n = 38); end-stage renal disease (n = 42). Plasma cytokines (TNFαα, IL-6, IL-8, IL-10), acute-phase C-reactive protein (CRP), cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR), and eosinophil cationic protein (ECP) were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA). The integral indices of systemic inflammatory reaction (SIR) have been calculated, i.e., a Reactivity Coefficient (RC) and a Reactivity Level (RL). In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

We have performed immunophenotyping of lymphocytes in 150 HIV-positive patients, by means of flow cytometry. All the persons under study were classified into three groups, depending on absolute contents of CD3+CD4+T-lymphocytes in peripheral blood, according to HIV infection staging in adults and adolescents, as amended by CDC (USA). It was revealed that, at each subsequent stage of disease, a decrease in absolute numbers of T-helpers is accompanied by drop in relative and absolute numbers of lymphocytes, as well as in total T-lymphocyte numbers, and decreased amounts of absolute cytotoxic T-lymphocytes levels, combined with increase in their relative contents, along with decreased CD3+CD4+/CD3+CD8+ ratio, diminished levels of double-positive subpopulation, decrease in relative and absolute levels of αβТ-lymphocytes and significant drop in absolute levels of γδТ-cells, while their relative amounts remained normal. These findings demonstrate a pattern typical to the absence of immunological reactions in response to antigens persisting in the organism.

Abstract. An intracellular staining technique of marker cytokines was applied for evaluation of quantitative distribution of T-lymphocyte effector subsets in children and adults. The results of this study have shown that the numbers of Th2 lymphocytes in infants (7 to 12 months old) correspond to appropriate normal values in adults, being accompanied by decreased Th1 and Тс1cell contents, whereas absolute amounts of Tc2 lymphocytes proved to be higher than in all other age groups. Absolute counts of Th17 and Tnc17 subsets in infants of 7 to 12 months were higher than in adults. Hence, these infants exhibited a shift of immune response towards Th2 (Tc2) and Th17 (Tnc17), thus presenting a potential factor of Th2-mediated allergic disorders in the children under one year. In children over 1 year, absolute amounts of Th1 and Тс1, as well as Th2 and Тс2 lymphocyte counts did not significantly differ from adult values. Th2 lymphocyte counts among adolescents (15 to 18 years) were decreased, along with relative increase of IL-17А-positive lymphocyte scores, thus reflecting a probable predisposition for autoimmune disorders induced at this age. The age-dependent increase in Th1 and Тс1 counts in children may immediately correlate with formation of T-cell memory pool.

Abstract. The lecture presents current data, as well as authors’ view to the issue of immune system involvement into inflammation. General physiological principles of immune system functioning are considered in details. Immunological mechanisms of local inflammation and participation of immune system components are analyzed with regard of protective/adaptive reactions in inflammatory foci. Original formulations of basic concepts are presented from the viewpoint of pathophysiology, immunopathology and clinical immunology, as being applied to the issues discussed. (Med. Immunol., 2011, vol. 13, N 6, pp 557-568)

Abstract. We performed a study of efficiency for various immunocorrective drugs in a group of 548 young schoolchildren with recurrent respiratory infections. Frequency of respiratory infections and complication rates were taken as endpoints in this study. It was revealed, that preventive immunocorrection by bacterial lysates or glucosamine muramildipeptide combined with vitamin-mineral complexes may reduce frequency of respiratory infections and their complications at statistically significant levels, as well as to restore some abnormal parameters of immune profile, i.e., CD3, CD4, CD16, induced NBT test, IFNγ, TNFα and IgG. Preventive use of Echinaceae purpurae herbae succus or interferon alpha-2b in combination with vitaminmineral complexes statistically significantly reduces only the frequency of respiratory infections, and partially restores some deficient parameters of immune status (IgG, TNFα, CD16). Introduction of preventive immunocorrection in childhood institutions, with > 90 % coverage of children with recurrent respiratory diseases is associated with a decrease in frequency of respiratory infections not only in this cohort, like as among general population of the same age group.

Abstract. The role of hepatitis C virus (HCV) co-infection in violation of restoring CD4+T cells in HIVinfected patients receiving antiretroviral therapy (ART) was investigated. Seventy eight patients with effective virological response to ART (viral load < 50 copies/ml) who either had or had no good immunological CD4+Tcell response after two years of treatment were recruited. Twenty one relatively healthy volunteers served as controls. The numbers of main T-lymphocyte populations and their apoptosis rates were determined. Thymus productive function was assessed by the number of αTREC-positive CD4+ and CD8+T cells. It is shown that HIV/HCV co-infection is characterized by lower numbers of CD4+T-lymphocytes in patients’ blood compared with HIV-monoinfection. This is not associated with the cells’ increased death rates. We also demonstrate that HCV coinfection reduces the production of CD4+, but not CD8+T-lymphocytes, by the thymus.

1222 patients with suspicion of different autoimmune connective tissue diseases are investigated. Antinuclear antibodies by indirect immunofluorescence reaction, by methods of ELISA and immunoblotting were determined. Laboratory tests results correlated with each other that testifies to satisfactory comparability of different laboratory methods. The most sensitive method for detection of antinuclear antibodies is indirect immunofluorescence. This is a preferable method for screening of autoimmune connective tissue diseases. At comparison of luminescence types in immunofluorescence test and results of immunoblotting was shown that for each type of a luminescence the set of antibody, revealed by immunoblotting, was characteristic. However, the same antibodies can be found in various types of fluorescence that complicates unequivocal interpretation of immunofluorescence test results. Antibodies to Ro-52 were most often found in all types of fluorescence, and also in the absence of that.

Aim. To study different inflammation markers at various stages of atherosclerosis progression.Material and methods. In 174 21-70-year-old people, brachial artery ultrasound (Aloka 5000) was performed to visualize atherosclerotic plaques and assess intima-media thickness (IMT). Immuno-enzyme analysis was used to measure plasma levels of C-reactive protein, CRP (SeroELISA test system, Diagnostic Systems Laboratories, USA), and cytokines — tumor necrosis factor alpha (THF-alpha), interleukins 1, 4 and 8 (IL-1, 2, and 8) (Russian test systems, Cytokine company, St. Petersburg).Results. The levels of CRP, IL-1, IL-8 and TNF-alpha were dependent on atherosclerotic process stage and IMT CRP levels typical for systemic inflammatory reaction were observed in individuals with subclinical atherosclerosis and patients with post-infarction cardiosclerosis.Conclusion. There was an association between IMT and latent inflammation activity. Qualitative changes in inflammation intensity were observed even at early stages of atherosclerosis development.

The article deals with the study of influence of autovenous ultraviolet irradiation of blood (AUIB) in monotherapy and in combination with acetylsalicylic acid on hemostasis state in patients on out-patients rehabilitation stage after myocardial infarction. 26 men were included in the study. 16 patients of the first group were underwent by 5 procedures of AUIB; 10 patients of second group combined A UIB with acetylsalicylic acid intake 250 mg daily. As the most strongly pronounced effect of AUIB was blood fibrinolytic system activation. The significant increase of soluble fibrin-monomer complex (SFMC) level was revealed that by indirection could testify to pro-thrombotic effect of method. Combined therapy by AUIB and acetylsalicylic acid resulted in increase of antiaggregant action and reduce the number of SFMC.

The state of the immune system was studied in the women working at the OAO Uralkalii (Berezniki) and OAO Sil'vinit (Solikamsk), where they were permanently exposed to salts and halite waste, and their children born after at least three years of such exposure. The control group consisted of women who had no occupational contact with salts and halite wastes and of their children. No significant differences between the differential leukocyte counts and immunograms of the women working at the OAO Uralkalii and OAO Sil'vinit and their children were found. The main parameters of the immune system of women and their children both in the first and second groups were within the norm. [ABSTRACT FROM AUTHOR]

Acute and chronic hypoxia led to acceleration of proliferation and differentiation of bone marrow megakaryocytes and increase in their functional activity. The count of young cells in the peripheral blood increased during acute hypoxia. Chronic hypoxia led to increase in the number of old platelets with lower functional activity, which was accompanied by thrombocytosis. [ABSTRACT FROM AUTHOR]

Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.

We defined Systemic inflammation (SI) as a "typical, multi-syndrome, phase-specific pathological process, developing from systemic damage and characterized by the total inflammatory reactivity of endotheliocytes, plasma and blood cell factors, connective tissue and, at the final stage, by microcirculatory disorders in vital organs and tissues." The goal of the work: to determine methodological approaches and particular methodical solutions for the problem of identification of SI as a common pathological process. SI can be defined by the presence in plasma of systemic proinflammatory cell stress products-cytokines and other inflammatory mediators, and also by the complexity of other processes signs. We have developed 2 scales: 1) The Reactivity Level scale (RL)-from 0 to 5 points: 0-normal level; RL-5 confirms systemic nature of inflammatory mediator release, and RL- 2-4 defines different degrees of event probability. 2) The SI scale, considering additional criteria along with RL, addresses more integral criteria of SI: the presence of ≥ 5 points according to the SI scale proves the high probability of SI developing. To calculate the RL scale, concentrations of 4 cytokines (IL-6, IL-8, IL-10, TNF-α) and C-reactive protein in plasma were examined. Additional criteria of the SI scale were the following: D-dimers>500ng/ml, cortisol>1380 or

The basic problems of current socio-demographic development of Russian regions are considered raising the need to find socio-economic and socio-psychological reasons for current demographic tendencies. Th eoretical substantiation of a demographic situation in Russia taking into account characteristics of the second demographic transition and influence of social stress has been given. Definition of the concept “eff ective sociodemographic development of a region” owing to synergetic effect in terms of socio-economic and demographic system interaction has been suggested. The forecasting method of socio-demographic region development on the basis of sharing of synergy and simulation modeling has been offered. Probabilistic forecasts of the population size of the Constituent Entities of the Russian Federation being parts of the Ural Federal District till 2025 have been obtained; the given forecasts are to estimate possible ways of socio-demographic development of the Ural Federal District.