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Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease, the development of which is associated with impaired mechanisms of cell number control, proliferation balance, and apoptosis. The aim of our study was to perform a comprehensive analysis of cellular and humoral effects exerted by “apoptotic” T lymphocyte culture upon “proliferating” cells, taking into account the parameters of “primary” and “secondary” apoptosis induction, activation and proliferation markers, viable cell contents, role of cortisol, caspase and cytokines during cultivation under the “cell neighborhood” conditions in healthy subjects and patients with RA. The results of the analysis, with respect to previous data, revealed both similar and different functions of the T cell systems generated under “cell-neighborhood” conditions in healthy individuals and RA patients. Both groups under study were characterized by secondary induction of apoptosis, which refers to non-autonomous effects, along with appearance of activated T lymphocytes at significant amounts, increase of IL-6 and IL-4 levels, as well as low levels of IFNγ and caspase 8, decrease potential of receptor and mitochondrial apoptosis. No differences in apoptosis level were found between donor and patient groups. At the same time, the initially high level of TNFα in healthy subjects decreased during the induction of apoptosis, along with moderate increase of IL-6. The levels of intracellular p53 and Bcl-2 molecules did not change, and many positive correlations remained between the studied factors in all variants of mixed and “apoptotic” cultures, thus suggesting maintenance of functional T cell balance under the unfavorable conditions in donors. The RA patients were characterized by increased number of live cells in “apoptotic” cultures, a significant increase in the number of Ki-67+ T lymphocytes, being indicative for proliferative processes under conditions of apoptosis, like as absence of TNFα response to apoptosis induction. Lack of relations between the studied molecules in “apoptotic” cultures and local cortisol synthesis, as well as presence of correlations between cortisol and the studied molecules in apoptotic cultures, presumed some changes of intercellular interactions and disturbance of homeostasis among T lymphocytes under the conditions of “cellular neighborhood” were also observed in RA patients.

Aim: to substantiate the expediency of using a segment of the jejunum on a vascular pedicle in esophagoplasty. Materials and methods. At the National Medical Research Center of Surgery named after A.V. Vishnevsky, 12 patients underwent esophagoplasty with a combined visceral transplant, of which 9 (75.0 %) received a gastrointestinal graft and 3 (25.0 %) — a colon-jejunum one. Esophagectomy with simultaneous esophageal plastic surgery was performed in 10 (83.3 %) patients, in 4 (40 %) of them — in combination with distal gastric resection. The indication for surgery in 3 patients was cicatricial stricture of the esophagus and stenosis of the pylorus, in 2 — achalasia of the cardia of the terminal stage (in one patient — with ulcerative stenosis of the pylorus). Three more patients underwent esophagectomy due to peptic strictures: esophagogastroanastomosis (n = 1), esophagoenteroanastomosis (n = 1) and esophagus after Nissen surgery (n = 1). Cancer recurrence after proximal gastric resection and gastrectomy in 2 patients was an indication for esophagectomy. Also, 2 (16.7 %) patients were hospitalized in the National Medical Research Center of Surgery named after A.V. Vishnevsky with incomplete esophagoplasty: one person — after Dobromyslov — Torek surgery for spontaneous rupture of the esophagus, and one patient — after the unsuccessful Lewis surgery for esophageal cancer performed in other hospitals. Results. The average duration of post-operative stay was 12.7 ± 6.3 days. The postoperative period was smooth in 10 (83.3 %) patients. The failure of the cervical anastomosis was revealed in 1 (8.3 %) patient on day 5 after esophageal plastic surgery with colon-jejunum graft, which was resolved conservatively without repeated surgery. Relaparotomy was required in one patient on day 7 after surgery for bile peritonitis, the cause of which was destructive acalculous cholecystitis with perforation. All 12 patients were discharged from the clinic with full nutrition through the mouth. In the long-term period, 11 (91.7 %) patients remained under observation, 1 (9.1 %) developed an esophagogastroanastomosis stricture 1.5 months after esophageal plastic surgery, which was resolved by 4 courses of bougation during the first 9 months after surgery. No other complications were noted. Conclusion. The segment of the jejunum on the vascular pedicle, used for esophagoplasty, in the condition of a shortage of plastic material, allows not only to complete the reconstruction at once, but also to restore the natural passage of food and prevent bile reflux.

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory joint disease, often associated with psoriasis. Interactions between immune cells, mainly T lymphocytes, and cells of the osteoarticular system are central in the pathogenesis of PsA. Th1, Th17 cytokines associated with the development of PsA contribute to an increase in the production of cytokines, chemokines, matrix metalloproteinases, adhesion molecules by immune cells, chondrocytes, fibroblasts, and induction of osteoclasts. That leads to the destruction of cartilage and bone tissue. Among the cytokines potentially involved in the pathogenesis of PsA, IL-7 is of particular interest. IL-7 is a T cell survival factor. However, it can promote the production of IFNγ and TNFα by T cells. IL-7 may indirectly promote osteoclast maturation and cartilage degradation. The aim was to investigate the effect of IL-7 and blockade of the α-chain of the IL-7 receptor (IL-7R) in vitro on the production of IL-5, IL-13, IL-2, IL-6, IL-9 IL-10, IFNγ, TNFα, IL-17A, IL-17F, IL-4, and IL-22 by T cells in norm and PsA.The study included 14 patients with PsA in the acute stage of the disease and 8 healthy individuals. To determine cytokines concentration, multiplex analysis was performed using flow cytometry.It was shown that IL-7 enhances the production of Th1, Th2, Th17, Th22, and Th9 cytokines in both patients with PsA and healthy individuals. The exception was IL-2 for both groups. Under the blockade of IL-7R with monoclonal antibodies, the level of IL-6 increases and production of IFNγ, TNFα, IL-17F, IL-10, IL-5, and IL-9 by donors’ cells and production of IFNγ, TNFα, IL-22, IL-2, IL-4, IL-5, IL-13, and IL-9 by cells from patients with PsA decreases relative to production of cells stimulated with IL-7. In donors, the blockade contributed to a change in the balance of Th1/Th2 cytokines: level of IL-4, IL-13 did not change on the background of a decrease in production of IFNγ, TNFα. In patients with PsA, under blockade of IL-7R the production of IL-10 remained at an increased level and concentration of IFNγ, TNFα and IL-2, which are actively involved in the tissue damage mechanisms, decreased. The obtained data indicate the prospect of using the IL-7R as a target for the treatment of psoriatic diseases.

One of the modern approaches to the treatment of cancer is the creation of targeted delivery systems for anticancer drugs, which allows increasing the concentration of the delivered substance in the right place and preventing its accumulation in healthy organs and tissues. At the same time, one can also expect an increase in the duration and effectiveness of the drugs, as well as a reduction in side effects during therapy. The hyaluronic acid receptor CD44, which, according to the literature, is highly expressed in many types of tumors and regulates metastasis, is a promising target for targeted delivery of anticancer drugs. The purpose of this study was to evaluate the effect of a supramolecular delivery system based on hyaluronic acid with nanosized cavitand cyclodextrin on the antitumor properties of oxaliplatin in vitro. Cell lines 1301, SK-MEL-28 and B16 were used as tumor cells. Cells were cultured in the presence of a delivery system based on hyaluronic acid (HACD), oxaliplatin (OX), and their complex (HACD-OX) at various concentrations in complete culture medium RPMI-1640 containing 0.3% L-glutamine, 4% gentamicin and 10% inactivated FBS serum for 48 hours in a humidified atmosphere of 5% CO2 at 37°C. The effect of the studied compounds on the viability of cell cultures was assessed using the WST test. It was shown that in the case of the T-cell lymphoma cell line 1301, the HACD delivery system did not affect the ability of OX to reduce the viability of tumor cells of this line; the effect of free oxaliplatin and the complex was comparable. However, in the case of melanoma cells (B16 and SK-MEL-28), the HACD-DOX complex has a more pronounced antitumor effect, causing a statistically significant decrease in the viability of B16 and SK-MEL-28 cells compared to free oxaliplatin.

Objectives. The study set out to investigate the sorption, toxicological, and regeneration properties of a composite sorbent based on chitosan hydrogel and unsuspended silicon dioxide (chitosan–colloidal silica), which manifest themselves under dynamic conditions of purification of aqueous solutions, as a means of removing heavy metal ions.Methods. The total dynamic exchange capacity of a chitosan–colloidal silica composite sorbent was evaluated under dynamic sorption conditions by passing solutions containing Zn(II), Cd(II), Cu(II), and Cr(III) ions having a concentration of 240–251 mg/L through a fixed sorption bed. The method for determining acute toxicity using daphnia (Daphnia magna Straus) is based on the direct calculation of the mortality of daphnia exposed to toxic substances contained in the test aqueous extract in comparison with a reference culture in samples that do not contain toxic substances. The regeneration ability of the sorbent was assessed by counting the number of sorption–desorption cycles using 0.1 M NaOH and 0.1 M NaHCO3 eluents, as well as aqueous solutions of H2O2 (1 and 3%).Results. The effectiveness of the chitosan–colloidal silica composite sorbent in the process of dynamic purification of aqueous media to remove Cu(II), Zn(II), Cd(II), and Cr(III) ions was established. After determining the times of ion breakthrough and saturation of the developed sorbent, its dynamic exchange capacity was calculated by processing the kinetic curves of sorption of heavy metal ions under dynamic conditions. The results of regeneration of the sorbent were presented in the context of the possibility of its reuse. It is shown that the sorbent can withstand up to five sorption–desorption cycles while maintaining a level copper cation extraction above 90%.Conclusions. Analysis of the kinetic curves demonstrated that the driving force behind the removal of heavy metals from aqueous media by means of the obtained sorbent is the external diffusion mass transfer of ions from the mobile phase of the solution. Biotesting of samples showed that the developed chitosan-based sorbent does not have acute toxicity.

BACKGROUND: Half of all patients with chronic heart failure (CHF) have preserved ejection fraction (CHF-nEF). The drug’s use effective for treatment of CHF with reduced ejection fraction (CHF-nFV) reduces the hospitalization incidence but does not affect the cardiovascular incidence or overall mortality in patients with CHF-nFV. Finding differences between CSN-SFV and CSN-nFV biomarkers is a pressing scientific problem.AIM: To study the metabolic disorders biomarkers intergenic relationships, myocardial damage, and to evaluate their role in the CHF development in patients with DM2.MATERIALS AND METHODS: We studied the lipid and carbohydrate metabolism disorder genes polymorphisms frequencies in patients with CHF-CFV and DM2 (48 patients), CHF-NFV and DM2 (46) and patients with metabolic syndrome (MS) without CHF (68), mean age of patients was 69,7±5,3 yo. DNA was isolated from venous blood according to the manufacturer’s methodology. Gene polymorphisms were determined by real time PCR. The studied polymorphisms correlations with clinical and laboratory data and associations between clinical and laboratory tests were identified by regression analysis.RESULTS: In the control group, PPARG, APOC3 C3238G rs5128, LIPC -250 G>A rs2070895, APOA1 G-75A rs670, FABP2 Ala54Thr G>A rs1799883, ADRB2 5318 C>G rs1042714 genes polymorphisms, along with co-dependent ADRB3, FTO, FABP2 genes polymorphic form a gene network regulating plasma concentrations of LDL, uric acid and CAD. Gene polymorphisms have been found to be associated with clinical and/or laboratory parameters in patients with CHF-CFV: PPARGC1AGly482Ser G>A rs8192678 with CAD; PPARGT-2821C rs12497191 with glycated hemoglobin level; FTO A>T rs9939609 (α-ketoglutarate dependent dioxygenase gene) with waist circumference; LEPR A>G rs1137101 (leptin receptor gene) with MAP. The following polymorphisms were found to be associated in patients with CHF-nFV: LIPC-250 G>A rs2070895 (liver triglyceride lipase gene) with MAP; PPARGC1A Gly482Ser G>A rs8192678 with MAP; FTO A>T rs9939609 with waist volume.CONCLUSIONS: From the study results, it is evident that patients with DM2 having CHF with different PV differ significantly among themselves by the presence of polymorphic genes prone to network interactions. The greatest number of such interactions is observed in the group of CHF-sFV, which determines a more complex course of this variant of CHF than in patients with CHF-nFV.

The ageing process should be considered with respect to all homeostatic systems of the body, their importance for the existence of the organism itself and different timing of their switching-on in the process of age-related changes. An attention should be paid to the literature data on age-related changes in the functional activity of immune system, which starts from almost zero at birth, reaches a maximum at the age of about 40-50 years and significantly decreases during the natural ageing process. The vast majority of most socially significant diseases of modern humans are reasonably associated with this last stage of age-related changes in the functional activity of the immune system. So far, there is probably no consensus on whether ageing is a disease, or not a disease, but just a kind of natural wear of the “biological machine”. In any case, one should emphasize that thymic gland is one of the first organs where negative age-related changes are revealed, one of the two central organs of the immune system. Bone marrow is the second central immune organ. Age-related changes in the thymus are not “all or nothing”, “now or never”, they are normally characterized by a gradual decrease of the cell production and changes in their qualitative characteristics, which undoubtedly result into some negative effects upon the indices of immune system activity. There is a need to develop new approaches towards the assessment of functional parameters of the thymus, highlighting the search for therapeutic approaches that would maintain functional activity of the immune system at a high level.

BACKGROUND. Patients with type 2 diabetes mellitus (DM2) have disorders of cellular and plasma hemostasis independent of the level of glycemia, increased platelet activation, combined with microvascular angiopathy. The study of the role of genetic markers of hemostasis disorders in the formation and progression of chronic heart failure (CHF) in patients with type 2 diabetes will allow for prevention, possibly optimize treatment and improve prognosis.AIM. To reveal polymorphisms of genes of the hemostasis system in patients with type 2 diabetes mellitus and chronic heart failure with preserved ejection fraction.MATERIALS AND METHODS. The frequency of coagulation factor genetic polymorphisms was studied in patients with CHF-pEF and DM2 (52 people), CHF with reduced ejection fraction (CHF-rEF) and DM2 (49) and healthy volunteers (66), mean age 69.9±10.1 years old. DNA was isolated from venous blood according to the method of the manufacturer. Genetic polymorphisms were determined by real-time polymerase chain reaction.RESULTS. The frequencies of polymorphisms rs1799963 and rs6025 of the genes of blood coagulation factors F2 (prothrombin) and F5 (factor V of blood coagulation) in all three groups were insignificant and comparable in magnitude. In patients with CHF and DM2, the frequencies of the rs6046 polymorphism of the factor F7 gene in the heterozygous form were slightly higher (by 2.6 and 1.7 times, respectively) than in the control group, but the result was not statistically significant. The CHF-pEF and CHF-rEF groups differ in the frequencies of F13 (rs5985) and fibrinogen (rs1800790) genetic polymorphisms, but are more common in patients with CHF-rEF and DM2.CONCLUSION. Based on the results of the study, it follows that the groups of CHF-pEF and CHF-rEF differ significantly in the frequencies of polymorphisms of the studied genes, both among themselves and with the control group. The highest frequency of polymorphisms of genes, the products of which are involved in the coagulation and cellular components of hemostasis, is observed in the group of patients with DM2 and CHF-rEF.

Autoimmune diseases currently take a leading place in terms of frequency of occurrence in the population, among which 1 percent is occupied by rheumatoid arthritis (RA). Remission in this type of disease is extremely rare and requires constant use of pharmacotherapy. Studying the pathogenesis of RA is necessary to study to search for new drug targets. It is known that T helpers 1 (Th) and Th17 are involved in the development of RA. However, some researchers suggest that ILCs play a role in the development of RA. ILCs are “innate analogues” of Th, due to the fact that this subpopulation synthesizes the same cytokines. ILC1 is innate analogs of Th1, ILC2-Th2, ILC3-Th17. ILCs are tissue-resident innate lymphoid cells that have functional diversity and regulate the direction of the immune response through the production of cytokines.We used peripheral blood mononuclear cells (PBMCs) from patients (n = 19) and conditionally healthy donors (n = 10) as material. The group of patients was divided biologic disease-modifying anti-rheumatic drugs (bDMARDs) and Metotrexate (MTX) and of stage of RA (early and very early arthritis, advanced and late). PBMCs were stained with monoclonal antibodies. ILCs were identified as Lin-CD127+, CD294+ILCs (ILC2) were measured in the general population, CD117-CD294-ILCs were identified as ILC1, and CD117+CD294-ILCs were identified as ILC3.We obtained the following results: ILC1 was significantly reduced in patients treated with MTX comparison with patients on bDMARDs and healthy donors. However, patients on MTX with advanced RA had low levels of ILC2 and ILC3 compared to patients on bDMARDs. ILC2 significantly increased in patients with early stages of RA comparison with patients with advanced RA. However, ILC1 was significantly reduced in patients treated with MTX, and ILC3 increased significantly in patients treated with MTX comparison with bDMARDs. Expression of PD1 on ILC1 was increased compared to patients treated with bDMARDs. However, ILC3 patients with advanced stages on MTX had increased expression of PD1 comparison with patients taking bDMARDs. The ILC3 of donors was significantly increased comparison with patients on bDMARDs.

Tumors are a leading pathology in the population. Chemotherapy cannot provide adequately and effectively to cure patients. Some medicine, such as cytostatic, are characterized by a wide range of side effects and resistance of solid tumors to chemotherapy by these medicines. In recent research, the mechanisms of action of cytotoxic agents have been described, and the most appropriate causes of resistance have been suggested. Drug delivery system based on Cucurbit[7]uril (CB[7]) was used to minimize side effects and overcome resistance. CB[7] has ability to form host-guest supramolecular complexes with oxaliplatin and carboplatin.It is important to consider the immune system maintain to a great role, and platinum compounds are able to have an immunomodulatory effect on immunocompetent cells. There is convincing evidence about the cytotoxic response against tumor cells is also associated with immunomodulating properties. A specific immune microenvironment with high frequency of suppressor cells is made by tumors. FoxP3+ regulatory T cells are recruited by the tumor, an increased number of these cells and expression levels of CTLA-4 and PD-1 on them contribute to the progression of the tumor process. These markers correlate with recurrence and poor survival of the patients. Therefore, it is necessary that antitumor therapy agents have an effect on a subpopulation of regulatory T cells and their functional activity. This study evaluated the effects of cucurbit[7] uril, platinum compounds, and supramolecular complexes on FoxP3+ regulatory T cells and the expression of immune checkpoint molecules.In this study peripheral blood cells from volunteers (n = 8, average 29.0±2.4) were used. Mononuclear cells obtained in the standard protocol were incubated for 72 h at concentrations of 0.3 and 0.1 mM for carboplatin and oxaliplatin, respectively, as well as complexes and CB[7] in equivalent dosages. Next, the samples were labeled with monoclonal antibodies to determine the phenotype and expression of immune checkpoint molecules by flow cytometry.We obtained the following results: The CB[7]-carboplatin complex in stimulated and non-stimulated cultures significantly reduced the number of FoxP3+ regulatory T cells compared to the control. At the same time, carboplatin and the CB[7]-carboplatin complex reduced the expression of CTLA-4 in an non-stimulated culture compared to CB[7].Complexes of Cucurbit[7]urils with platinum compounds are a perspective antitumor agent with immunomodulatory properties.

Research data presented in the article are based, mainly, on the concept that thymus, together with bone marrow represent the central organ of immune system being the source of all T cell populations that, following their migration from thymus to periphery, participate in development of immune response to any antigens of viral, bacterial and tissue origin, and to any allergens. This difference is principal, as opposed to the bone marrow which produces other members of immune response, i.e., dendritic cells, macrophages, B cells. E.g., the bone marrow also generates the cells which migrate to thymus where they undergo differentiation to the T cells. Over last 50 years, a plethora of data was accumulated on the leading role of immune system in pathogenesis of virtually all socially significant human diseases affecting the modern mankind, including infectious and malignant disorders, atherosclerosis, autoimmune and allergic diseases. Moreover, current studies show that the aberrant functions of different T cell populations play the leading role in pathogenesis of these diseases. These T cell disturbances in peripheral areas of different organs are proven to develop, mainly in the thymic area. Hence, thymus is a producing organ of T cells with altered functional activities which promote pathogenetic changes in these disorders. Currently, the entire set of immunotherapeutic approaches is aimed for correction of disturbances among the same T cells subpopulations at periphery, without taking into account thymic mechanisms which have induced these disturbances before their emigration from thymus. One should, therefore, develop novel methods and approaches to correct these alterations within thymic area.

Cellular homeostasis in the body is known to be maintained by the processes of cell proliferation and death, whereas apoptosis is the most frequent and physiological, “silent” mechanism of cell elimination. It has been currently shown that the process of apoptosis traditionally considered an autonomous event, has a pronounced non-autonomous effect on migration, proliferation, and death of the neighboring cells. This work was based on the data on impaired programmed death of mononuclear cells from the patients with rheumatoid arthritis (RA) leading to the evolving autoimmune inflammation. The aim of this study was to evaluate effector molecules exerting autonomous and non-autonomous influence of T cell apoptosis under the conditions of “cell neighborhood” in cell cultures of healthy people and RA patients. The studies were performed with blood samples of RA patients and healthy women of comparable age. These experiments were performed in order to assess the levels of main molecules mediating the in vitro receptor and mitochondrial apoptosis of T lymphocytes. In previous studies, using the original “cell neighborhood” model, no differences were found in parameters of early and late activation apoptosis between the groups of donors and RA patients. At the same time, 1-week incubation in apoptotic cultures of the patients was followed by significantly increased number of viable cells carrying the proliferation marker Ki-67. Different results of in vitro apoptosis induction in cultures under similar conditions of “cell neighborhood” in healthy people and patients with RA have revealed the importance of main effector molecules of apoptosis in the studied groups. In this study, we have revealed low potential of the receptor pathway for apoptosis activation in healthy people, due to suppression of TNFα production during cell incubation under the conditions of “cell neighborhood”, and in RA patients due to initially low TNFα in supernatants which did not change over time and in various incubation variants, along with low content of initiating caspase 8 in both groups. Significant suppression of effector molecules of mitochondrial pathway of apoptosis activation, i.e., Bcl-2 anti-apoptotic factor and p53 transcription factor was detected in cultures of apoptotic cells, as well as mixtures of proliferating and apoptotic cells under the conditions of “cell neighborhood” in RA patients. The amounts of these molecules did not change in healthy persons. At the same time, no differences in these molecules were found between individual variants of cell cultures from the patients with RA and healthy people. The both studied groups were characterized by a significant activation of IL-4 and IL-6 production, i.e., the cytokines with autonomous and non-autonomous protective and reparative properties, Hence, one may conclude that high levels of these cytokines had different effects in cell cultures under the conditions of “cell neighborhood”. Incubation of cells from healthy people under suboptimal conditions was associated with maintaining the balance of proliferation and apoptosis, whereas, in cell cultures of RA patients, this balance caused activation of proliferation processes, being accompanied by an increase in the number of living cells in apoptotic cultures.

Background. Due to their very small size, nanomaterials, in particular cucurbiturils, have unique physical and chemical properties that find their application in medicine. However, the toxicity of cucurbiturils is not fully understood; in particular, we are interested in the immunological safety of their use. One of the mechanisms of nanotoxicity is the formation of reactive oxygen species (ROS) by macrophages and neutrophils. Hyperproduction of ROS can lead to oxidative stress and further damage to cell DNA with loss of physiological function and development of pathology. The aim. Evaluation of the effect of cucurbit[n]urils (n = 6, 7, 8) on the production of reactive oxygen species by mice macrophages and neutrophils. Materials and methods. F1 hybrid mice (CBAxC57Bl/6) aged 2 months (n = 11) were used in the work. Evaluation of superoxide radical production by peritoneal mouse neutrophils and macrophages was carried out by spectrophotometric method for determining the reduction of p-nitroblue tetrazolium (NBT) to formazan. Results. It was shown that CB[6] and CB[7] at concentrations of 0.5 and 0.3 mM do not have an inhibitory effect on ROS synthesis, but, on the contrary, significantly increase ROS production by macrophages. In addition, CB[6] 0.3 mM increases the level of ROS in neutrophils. Conclusion. Cucurbiturils can lead to an increase in the production of ROS in immunocompetent cells, depending on the concentration used (0.3 mM and higher).

Increased concentration of cell-free DNA (cfDNA) in the circulating blood of humans and animals is a sign of inflammatory conditions and a distinctive characteristic of various pathophysiological processes in the body. The aim of the present study was to investigate the possible role of tumor necrosis factor (TNFα) in changes of cfDNA contents in peripheral blood as a response to experimentally induced systemic inflammation.We used 40 female hybrid mice (C57Bl/6xDBA/2) F1 at the age of 6-8 weeks. The concentration of cfDNA and its individual fractions was determined using a PicoGreen fluorescent dye. The dynamics of inflammatory process was evaluated after 4, 8, 11 and 24 hours following LPS injection. A significant increase in the blood plasma cfDNA levels was shown under the action of E. coli lipopolysaccharide (LPS), along with simultaneous decreased levels of cfDNA, associated with cell surface. The ratio of cell surface-bound cfDNA to the total cfDNA contents was reduced in dose-dependent manner as early as 4 hours after LPS injection to the animals, thus allowing us to consider this ratio a characteristic sign of netosis of neutrophilic granulocytes during the development of acute inflammation. The described effects are significantly suppressed with co-injection of recombinant TNFα neutralizing protein along with LPS, whereas increased intake of neutrophils in the tissues is determined by some other factors which are not directly related to the production of this cytokine.Based on the obtained data, we proposed a following hypothesis: induction of netosis by inflammatory stimuli causes an increase in the concentration of cfDNA in blood plasma not only due to de novo emerging extracellular DNA by neutrophil netosis, but also by the release of distinct cfDNA fraction that was previously firmly bound to cell membranes in multiple body tissues under the action of proteases released during netosis.

Purpose. To study suppressor and/or cytotoxic activity of the nuclear erythroid cells (NEC) against tumor cells of various origins. Material and Methods. C57Bl/6 mice and P815, L1210, B16 and L929 tumor cells were used. “Phenylhydrazine” NECs were obtained from mice with induced hemolytic anemia. “Erythropoietin” NECs were isolated from the “phenylhydrazine spleen” and further cultured in the presence of erythropoietin. Another source of NEC was neonatal mouse spleen, human and mouse fetal liver cells, and mouse bone marrow cells cultured with erythropoietin. The cytostatic effect of NEC or their supernatants was recorded by reducing proliferation of P815, L1210, B16, LLC, L929 lines. Results. The presence of pronounced direct antitumor activity was found in both NEC and their culturing products in relation to cells of various tumor lines. The suppressor effect was not specifc. Conclusion. We know about the signifcant numerical predominance of NEC during the embryo development over all other hematopoietic cells and their high suppressive potential. Therefore, it can be assumed that erythroblasts are involved in process of creating antitumor protection of a fetus during this period of life.

Aim. To assess the impact of autologous activated T-lymphocyte immunotherapy on clinical parameters and quality of life in patients with allergic bronchial asthma (BA) in comparison with patients with allergic BA who received standard therapy.Materials and methods. A non-randomized, pilot study included 19 patients with allergic BA of moderate severity (7 men and 12 women aged 23–61 years, average age – 38.5 ± 4.3 years) who received the T-cell vaccine (n = 12) and standard therapy with inhaled glucocorticoids, short- and long-acting β2-adrenergic agonists (n = 7). After signing an informed consent, the patients were subcutaneously injected with autologous activated T-lymphocytes with a frequency of 4 injections 1 time / week, and then 6 injections 1 time / month. The research methods included asthma control measurement according to the ACQ-5 questionnaire and quality of life assessment according to the AQLQ(S) questionnaire. Clinical data were collected during lung function tests and by measuring the total immunoglobulin E (IgE) level.Results. In the course of the study, the immunotherapy was well tolerated, no systemic adverse reactions were noted. The treatment approach in the patients who received the T-cell vaccine resulted in significant improvement of asthma control parameters (according to the ACQ-5 questionnaire) and parameters of the patients’ quality of life (according to the AQLQ(S) questionnaire) within all 4 categories. Besides, their lung function improved by the end of treatment, and the total IgE level decreased. No significant changes in these parameters were observed during the follow-up in patients who received standard therapy. The study was conducted before immunotherapy, after 2 months (after 5 injections), and after 7 months (after 10 injections).Conclusion. Evaluation of the impact of immunotherapy with autologous activated T-lymphocytes on the clinical parameters and quality of life in patients with BA indicates effectiveness of treatment in patients with allergic BA.

Nanotechnology in immunology is a prospectively developing area in fundamental and practical medicine. Cucurbiturils are macrocyclic cavitands with a definite amount of glycoluril fragments (n) that determine the size of the cavity of these compounds. Nowadays, there are six synthesized homologues: 5, 6, 7, 8, 10 and 14. They differ from each other in the portal size and the size of the cavities. They are characterized by special physicochemical and biological properties, such as biocompatibility, stability, high ability to encapsulate chemical compounds. It is known that cucurbiturils encapsulate molecules by forming guest-host complexes, which allow the substance to be released from the complex and increase the solubility of the compounds. These advantages allow using cucurbiturils as drug delivery systems. Immunomodulatory activity of cucurbiturils depends on its specific nanoscale characteristics: functional groups, shape, size, surface, solubility in various media. Each nanoparticle depending on these properties has different effects on cells. The effects of cucurbiturils can be different even for one subpopulation of cells, depending on the homologue or dosage. The interaction of innate immune cells with cucurbiturils are not yet sufficiently characterized.The aim of this study was to assess the effects of cucurbit[n]urils (n = 6, n = 7, n = 8) on innate immune cells – monocytes, NK-cells, NKT-cells.The immunological recearch included the isolation of peripheral blood mononuclear cells from healthy donors (n = 8) on the density gradient of ficoll-urografin and flow cytometry with the determination of the amount of immunocompetent cells according to the classic markers of differentiation of these cells – CD3- CD16+CD56+ for NK-cells, CD3+CD16+CD56+ for NKT-cells and CD3- CD14+ for monocytes. Monocyte activation was determined by the expression of surface HLA-DR.The cells were cultured for 72 hours with the addition of cucurbiturils CB[6], CB[7] at concentrations of 0.1 mM, 0.3 mM, 0.5 mM and CB[8] at concentration of 0.01 mM, due to its poor solubility.There were a significant decrease in the quantity of NK-cells (p < 0.01 for the test concentrations of CB[7]), an increase in the quantity of NKT-cells (p < 0.04 and p < 0.02 respectively for the concentrations of CB[6] and CB[7]). There was a tendency to increase the expression of HLA-DR on monocytes (p = 0.06 for CB[6]).Considering a variative effects of cucurbiturils, in the future it is possible to consider a possibility of using cucurbiturils as an immunomodulators, antitumor agents, in autoimmune diseases.

Cytokines IL-7 and IL-15 are the most important humoral factors providing T-conventional cell pool reconstitution during homeostatic proliferation caused by lymphopenia. However, whether these cytokines can provide homeostatic maintenance and proliferation of T-regulatory (Treg) cells is largely unknown. Considering the association between homeostatic proliferation and the development of autoimmunity, we decided to investigate the ability of these factors to cause differentiation of Treg-cells into Th17-lymphocytes. Therefore, the purpose of this study was to investigate the influence of humoral factors of homeostatic proliferation (IL-7 and IL-15) on Treg-cells in vitro. The study used peripheral blood sampled from 22 healthy donors. PBMC fraction was isolated by Ficoll density gradient centrifugation. Proliferation was induced by IL-7, IL-15, and by a combination of IL-2 with anti-CD3-antibodies. The proliferation intensity of Tregs was evaluated by flow cytometry using CFSE in PBMC cultures by phenotype CD3+CD4+CD25+FoxP3+ and in the previously purified population of CD3+CD4+CD25+CD127lo-cells. In this case Treg-cells were obtained by immunomagnetic separation from PBMCs using a MACS Treg Isolation Kit. Also, the RORyt expression in CD3+CD4+CD25+FoxP3+-cells was evaluated during cultivation. Here, we have shown that IL-7 and IL-15 could support Treg-cells by number and phenotype. Also, we revealed that these factors provide FoxP3 expression in Treg-cells; meanwhile, stimulation with IL-2 + anti-CD3 can also cause induction of FoxP3 expression de novo in conventional CD4+ cells. Also, we have shown that IL-7 and IL-15 can cause lower-intensity proliferation of Treg-cells in comparison with IL-2 + anti-CD3. Herewith homeostatic cytokines didn’t have the ability to induce RORyt expression in both T-regulatory cells and CD4+ conventional T-lymphocytes. Thus, it has been shown that IL-7 and IL-15 can potentially participate in maintaining the total pool of Treg-cells during lymphopenia, when IL-2 deficiency occurs, without causing the induction of RORyt expression. However, how homeostatic cytokines affect the functional activity of Treg-cells remains unclear and requires further investigation.

Much attention of researchers is directed to study the role of factors of homeostatic proliferation in the pathogenesis of autoimmune diseases, however, the effect of IL-7 and IL-15 on the phenotype of naive T cells has not yet been sufficiently investigated in the pathology. The aim of this study was to investigate the proportion of CD45RA+ and CD31+ naive cells among CD4+ and CD8+ lymphocytes from healthy individuals and patients with rheumatoid arthritis (RA) upon stimulation with IL-7, IL-15 in vitro. In peripheral blood, we did not find any differences in the number of CD45RA+ and CD31+ cells between the group of donors and group of RA patients. In donors, stimulation by a combination of IL-7 with IL-15 promoted an increase in the proportion of CD4+CD45RA+ and CD8+CD45RA+ relative to their level in the peripheral blood. Whereas in RA patients the number of CD8+CD45RA+ cells decreased under IL-15 and the combination of IL-15 with IL-7 compared to the control without stimulation, and it, as a proportion of CD4+CD45RA+ cells, significantly differed from the content of these cells under the same conditions in donors. There were no significant differences in the content of CD31+ cells and the number of CD31+ cells proliferating to cytokines, both between the groups of donors and patients with RA, and between different culture conditions. Thus, we can say that under the factors of homeostatic proliferation, there is a proportional increase in CD31+ T cells number, both in donors and in patients with RA. At the same time, naive T cells from donors retain the expression of CD45RA during cultivation, while naive T cells from patients partially lose it. The obtained data indicate that in RA, under factors of homeostatic proliferation the phenotype of naive T cells is converted into the phenotype of memory T cells.

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.

Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by quantitative (type I) or functional (type II) deficiency in C1 esterase inhibitor (C1-INH). It may be caused by new mutations in up to 20% of patients. Prevalence of HAE is uncertain but is estimated to be approximately 1 case per 50,000 persons, without known differences among ethnic groups. C1-INH protein is a serine protease inhibitor that is important in controlling vascular permeability by acting on the initial phase of the complement activation, blood clotting, and fibrinolysis. Deficiency in functional C1-INH protein permits release of bradykinin, a key mediator of vascular permeability. Symptoms typically begin since childhood, worsening at puberty, and persist throughout the life, with unpredictable clinical course. The patients with HAE suffer from recurrent, acute attacks of edema that can affect any body sites, causing potentially life-threatening disorders (laryngeal edema). Results of clinical studies show that minor traumas, stress and medical interventions may be frequent precipitants of swelling episodes, but many attacks occur without an apparent cause. Pregnancy-associated hormonal changes may affect the course of C1-INH angioedema attacks by worsening, improving, or having no impact at all, but a higher percentage of pregnant women experienced an increase in C1-INH-HAE attack rates. Therapeutic options for patients with HAE are limited during pregnancy. C1-INH concentrate is recommended as the first-line therapy for pregnant women with HAE for on-demand treatment, shortterm and long-term prophylaxis, due to its safety and efficiency. Other therapies, e.g., treatment with fresh frozen plasma, androgens, icatibant, antifibrinolytics, may show variable efficacy, or cause undesirable side effects. The case below illustrates the successful treatment of HAE in a pregnant woman with C1 esterase inhibitor (C1-INH) concentrate. This patient had a very mild course of HAE during her lifetime and didn’t get any treatment. During pregnancy, she experienced a significant increase in the frequency of attacks, and the decision was made to start replacement therapy with a plasma-derived, double virus-inactivated C1-INH concentrate as a long-term prophylaxis throughout the full term of her pregnancy, before, during and after the cesarean section delivery.

The process of apoptosis is known that play an important role in cellular homeostasis, and the altered cell death may lead to development of pathological disorders. Evolving autoimmune conditions, in particular, rheumatoid arthritis, are associated with decreased rates of apoptosis as a form of programmed cell death. The aim of this study was to evaluate expression of activation and proliferation markers on T lymphocytes during initiation of apoptotic cell death under the conditions of “cell neighborhood” in healthy individuals and patients with rheumatoid arthritis. Patients and methods. The study was performed with blood samples of the patients with rheumatoid arthritis (RA) and healthy women of comparable age. During the study, we conducted experiments aimed to identify the in vitro influence of non-stimulated apoptosis-induced cells, as well as aCD3- and dexamethasone (Dexa)-stimulated apoptosis-induced cells upon autologous T lymphocytes cultured under physiological conditions. Development of a “cell neighborhood” model, i.e., co-cultures of CFSE- T cells subjected to incubation under crowding condition and depletion of the culture medium which is the most physiological variant of apoptosis activation, and CFSE+ autologous cells placed in the complete culture medium, has revealed some relationships. We have revealed an opportunity of secondary induction of early and late apoptosis by means of humoral and cellular components of autologous cell culture subjected to activation apoptosis. We determined the features of apoptosis in unstimulated, as well as aCD3- and dexamethasone-stimulated cultures, compared with controls. There were no differences in these parameters of apoptosis between RA patients and healthy people for all variants of cultures. An increased proportion of viale cells was found in the CFSE- culture of patients with RA when compared to donors. The donor group had more lymphocytes with activation parameters CD25+, CD69+ and low level of proliferation marker Ki-67 than patients. In contrast to healthy, the RA patients demonstrated a significantly increased expression of Ki 67 in T lymphocytes when co-culturing CFSE- and CFSE+ cells. An increased number of living cells in apoptotic cultures of patients with RA relative to healthy people, in absence of significant differences in the parameters of apoptosis and activation markers in dynamics, as well as pattern of changes in the Ki-67+ cell contents suggested a contribution of the non-autonomous effects of apoptosis to cellular homeostasis in RA patients.

IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.

Lactobacilli are widely used in clinical practice as probiotics, biologically active additives and probiotic products for functional nutrition. Some probiotics can be considered as bacterial vaccines due to induction of immune response, accompanied by production of specific antibodies. The aim of the present study was to evaluate the state of cellular and humoral immunity in women by using probiotic strains of lactobacilli. The study included 31 healthy women aged 25-45 years. As a source of probiotic lactobacterial complex, we used the “Provag” preparation (RU 77.99.11.003.E.003746.02.11 of 11.02.2011, 1 capsule contains 109 Lactobacillus gasseri 57C, Lactobacillus fermentum 57A и Lactobacillus plantarum 57B). The drug was used for 30 days, at a rate of one capsule per day. The immune system was examined twice: before administering the drug and after 30 days of treatment. The study of blood lymphocyte populations and subpopulations was performed by flow cytometry using direct immunofluorescence technique. The concentration of IgA, IgM, IgG in blood serum was determined using enzyme immunoassay. To determine specific antibodies, we used passive hemagglutination reaction with erythrocyte diagnosticum. The complex of probiotic lactobacilli Lactobacillus gasseri, Lactobacillus fermentum and Lactobacillus plantarum corresponding to the “Provag” preparation was used as a source of antigen. It has been revealed that the number of T and B lymphocytes in peripheral blood increased after 30 days of treatment with the probiotic preparation “Provag” in healthy women. Elevated contents of T cells was due to the T helper cell fraction. Increased levels of T helpers and B lymphocytes were associated with stimulation of humoral immunity, as evidenced by increasing concentration of IgA and IgG in blood serum. By means of passive hemagglutination reaction, we have found that 90% of healthy women showed increased concentrations of specific IgA in blood after 30 days of treatment with “Provag” preparation.

There is no doubt that infectious agents and host undergo multilayered yet not fully understood interactions. This is primarily due to at least mechanisms resulting in chronic course of infectious process. Acute infection proceeds in parallel with primary immune response and its typical phases, each of which manifests as certain stage in clinical picture featured with disease onset and subsequent recovery. A whole process of immune response developing against infectious agent occurs in peripheral lymphoid organs and immune tissues. With regard to the role of immune system in infectious process, process, two main outstanding issues still remain unanswered: 1) what are the mechanisms of host death in the case of acute infectious process? 2) what is a “fault” of immune system in it? In its inferiority or in abruptly suppressed functions induced by infectious agent, when it “does not have time” to mount an immune response of sufficient power? So far, no answer is still found yet. The second question concerns mechanisms of converting to chronic course of infectious process. The obtained available in publications evidence about an intimately involved thymus as the central immune organ in infectious process of, the main function of which is to ensure developing central immune tolerance to self-antigens accomplished via T-cell positive and negative selection. It turned out that in case of some examined infections due to pathogens, which entered the thymus, such intimate events such as partial tolerance to pathogens and autoimmune reactivity are altered. Moreover, these processes are further aggravated by homeostatic proliferation, which is also induced by an infectious agent. In both cases, it accounts for decreased magnitude of immune response against a certain pathogen, burdened by emergence of autoimmune reactions.

Rheumatoid polyarthritis (RA) is an autoimmune disease with autoantibodies, including antibodies to citrullant antigens and proinflammatory cytokines, such as TNF-α and IL-6, which are involved in the induction of chronic synovitis, bone erosion, followed by deformity. Immunopathogenesis is based on the mechanisms of the breakdown of immune tolerance to its own antigens, which is characterized by an increase in the activity of T-effector cells, causing RA symptomatology. At the same time, against the background of such increased activity of effector lymphocytes, a decrease in the activity of a number of regulatory cells, including regulatory T-cells (Treg) and myeloid suppressor cells, is recorded. There is reason to say that it is the change in the activity of suppressor cells that is the leading element in RA pathogenesis. That is why only periods of weakening (remission) of RA are spoken of. According to the more powerful female immune system compared to the male one, the risk of developing RA in women is thrice as high, this risk decreases during breastfeeding and grows during pregnancy as well as after menopause in proportion to the level of sex hormones. It is believed that 50 % of the risk of developing RA depends on the conditions and lifestyle, while the remaining 50 % is dependent on genetic predisposition. That is why, RA fits the main idea of postgenomic predictive-preventive personalized medicine that is to give a chance to those who would like to reduce his/her risk of diseases by bringing his/her conditions and lifestyle in line with the data on his/her genome sequenced. This is very important, since doctors consider RA as one of the most frequent causes of disability. Using the Web service SNP_TATA_Z-tester (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl), 227 variants of single nucleotide polymorphism (SNP) of the human gene promoters were studied. As a result, 43 candidate SNP markers for RA that can alter the affinity of the TATA-binding protein (TBP) for the promoters of these genes were predicted.

In oncology, one of the leading places belongs to breast cancer. This problem is particularly significant in the current situation, when the issue of reproductive health of the female population is acute lyuped in connection with the unfavourable demographic trends in our country. Early diagnosis of precancerous diseases and initial stages of cancer is possible only with active search of patients among practically healthy people. However, despite the availability of breast for examination in adult clinics, malignant tumors of these locations are often found with considerable delay. The most important factor in the success of early diagnosis of oncopathology is the work of primary health care physicians. However, there have been no studies on the quality of early diagnosis of breast cancer in urban women in modern seffings. Purpose of the study. to study the quality of early diagnosis of breast cancer in urban women by doctors of adult polyclinics. Materials and methods. Adult clinics №.1, 2, 3, 4, 5, 6, 7, 8, 11, 12 of Ivanovo have been identified as the basis of the study. The study was conducted in 2018. The program of the study included the use of methods: expert, sociological, mathematical and statistical. Surveillance units: a woman with a malignant breast formation living in the city; case of detected and confirmed malignant breast formation. A retrospective analysis of 600 expert opinions was carried out, the survey method on the questionnaire studied women's satisfaction with premorbid prevention in the adult clinic and the availability of early diagnosis of breast cancer (100 patients). The data were processed using applied computer programs. Results. It has been established that the main causes of late diagnosis of breast cancer in urban women are: untimely treatment of the patient in a medical and preventive institution, deviations from the standard of examination of women for oncopathology, errors in diagnosis, features of the course of the disease (lightning or latent form), non-compliance with continuity in the management of the patient.Conclusion. Analysis of expert opinions on advanced cases of breast cancer showed that the bulk of the defects detected are preventable and are associated with low cancer of doctors and failure to fully and properly perform the standard of examination oncopathology.

The wood of Scots pine after 100–600-year exposure to anaerobic conditions was studied. The samples were taken from the soil during archaeological excavations in the city of Veliky Novgorod. It has been established that the destruction of the secondary wall layers (mainly S2 layer) of tracheids in the sapwood and heartwood occurred after 100 and 400 years of exposure, respectively. Archaeological wood contained mineral particles consisting of water-insoluble compounds of iron and potassium. The results of thermogravimetry showed the changes in the relative content of hemicelluloses, cellulose and lignin in the samples of archaeological wood. The proportion of hemicelluloses and cellulose in wood decreased by 8–13 % and the proportion of lignin increased by 6–9 % under the prolonged exposure to anaerobic conditions (400 and 600 years) compared to the samples of 100 and 200-year exposure. This was also confirmed by chemical analysis data. The oxidative thermal decomposition of the carbohydrate complex, as well as lignin started at lower temperatures indicating lower thermal stability of the main components of the wood substance. All the studied wood samples were characterized by a significantly higher proportion of residual mass after thermal decomposition compared to sound wood. This fact also suggested higher content of mineral substances. The total thermal effect of oxidative thermal decomposition of carbohydrate and aromatic components of the wood substance was noticeably higher (13.1 and 12.6 kJ • g–1) for the samples of 400 and 600-year exposure compared to those of 100 and 200-year exposure (8.9 and 10.8 kJ • g–1). Mono-and sesquiterpenes were found in wood, as well as diterpen 18-norabietan, the most resistant one to biological degradation, which accounted for 30–64 % of the total content of volatile organic substances. The obtained results indicated significant changes in the composition and structure of Scots pine wood after 400 years of exposure to anaerobic conditions.

The new economic policy of Russia is based on innovation and investment. Before choosing innovative changes, it is mandatory to assess the innovative potential of the organization. can distinguish Three main components can be distinguished in the innovative potential of a medical institution: innovative potential of medical personnel, innovation of facilities and resources, technology innovation (medico-institutional, therapeutic and diagnostic technologies). An audit of the innovative potential of a medical organization is a prerequisite for the formation of a competent economic policy, i. e. business strategies, priority investments. However, studies on a comprehensive assessment of the state of innovative potential of oncological medical organizations have not been conducted yet.Objective. To study the state of innovative potential of a medical organization, as part of its economic policy, using the example of cancer care.Materials and methods. The base of the research is the Higher Educational Institution “Ivanovo Regional Oncology Dispensary”, Department of Health, Ivanovo Region. The research program provided for the use of sociological, expert, mathematical-statistical and analytical methods. Units of observation: medical worker (doctor, paramedical worker) and material and technical resources of “Ivanovo Regional Oncology Dispensary”, The study was conducted in 2018. The integral estimation methodology of a medical organization’s innovation potential includes a quantitative assessment of each component of the potential according to the appropriate methodology.Results. Decline of the innovative capacity medical organization oncological profile on all of its components including: a personnel component at 9,0%, logistical component to 11,0%, technological component at 6,8%. Reduced innovative capacity of health workers is associated with low estimation of its parameters such as: the use of information sources for self-development, the ability to adapt to innovation and research activity. A decrease in the innovative potential of an oncological medical organization was noted in all its components, including: the personnel component by 9.0%, the material and technical component by 11.0%, the technological component by 6.8%. The decline in the innovative potential of health workers is associated with a low assessment of its parameters such as the use of information sources for self-development, the ability to adapt to innovation and research activities. The decrease in the innovation of the organization’s facilities and resources is associated with such indicators as: the scientific and technical level of equipment, the coefficient of accumulation of fixed assets, the coefficient of depreciation of equipment, the coefficient of inclusion of equipment in the standard of assistance. The decrease in innovation in the technological component is associated with the incomplete implementation of such quality attributes of medical services as: efficiency, adequacy, interpersonal interaction, uniqueness, convenience.Conclusion. The results of the study showed that a change in the innovative policy of medical organizations is required, its transfer from an extensive to an intensive strategic vector of development, the use of free financial resources for the purchase of new generation equipment, and the training of medical personnel in modern work technologies.

The aim of the study was to determine subpopulation content, proliferative activity and T-lymphocyte apoptosis level in adult mice-recipients that in the juvenile period underwent multiple transplantation of immune cells with different functional properties from opposite behavioral types of donors. Materials and methods. The study was carried out on male mice (CBAxC57BL/6) F1 (n = 190), which underwent transplantation of immune cells with definite functional properties three times starting from the age of 4–5-weeks. Phenotyping of recipients’ spleen cells was carried out by flow cytometry with monoclonal antibodies against CD3+, СD4+, CD8+. Splenocyte proliferation and apoptosis were estimated. Results. Animals that underwent threefold transplantation of immune cells from singeing opposite behavioral types of donors in the juvenile period revealed different functional properties of spleen lymphocytes in adults. The most pronounced changes were detected in the animals receiving the immune cells from donors with passive behavior type. The lymphocytes of these recipients were characterized by relatively low proliferative activity and T-mytogen sensitivity, decreased CD4+, CD8+ apoptosis level under deficient medium conditions and increased level of activation and dexamethasone-induced apoptosis in CD4+ lymphocytes.

The aim of the study was to evaluate cell-free DNA (cfDNA) in the follicular fluid (FF) of women undergoing IVF treatment and to analyze the relationship between cfDNA levels and the parameters of folliculogenesis and oogenesis as well as the quality of embryos. Materials and methods. The study included 53 women aged 20 to 45 years. In 49 patients, oocytes were obtained by stimulating ovulation with gonadotropins, and 4 patients underwent natural cycle IVF without hormonal stimulation. Measurement of cfDNA was carried out by fluorimetry using QuantiFluor™ Handheld Fluorometers (BioSilica, Russian Federation). Results. The FF of women with ovulation stimulation revealed a higher level of cfDNA as opposed to FF of women in the natural cycle. There were no differences in the cfDNA levels in women with infertility and oocyte donors. Women with infertility lasting for more than 5 years had a higher level of cfDNA. Women with the elevated anti-Mullerian hormone (AMH) levels were characterized by the high FF cfDNA concentration and a large number of follicles. Likewise, correlation analysis showed that FF cfDNA was significantly and positively correlated with the AMH level. The obtained data revealed the participation of cfDNA in different stages of oogenesis. Conclusions. The level of FF cfDNA in women may serve as an additional biomarker of the effectiveness of ovulation induction.

Bronchial asthma is a chronic inflammatory disease of the respiratory tract. T-lymphocytes play a key role in pathogenesis of this allergic disease. The reduction in number of naïve T cells and the accumulation of memory T cells in bronchial asthma are accompanied by dysregulation of T lymphocyte function. In present study, we have investigated the contents of different T lymphocyte subpopulations in peripheral blood as well as in resting and PHA-stimulated cultures, along with their proliferative capacity in patients with bronchial asthma and healthy donors. The study included 10 patients with bronchial asthma (age 45.4±11.8 years). One-half of patients was in remission state, the others having been at the stage of clinical exacerbation. The group of donors was formed by healthy individuals matched by gender and age to the patients. Based on expression of cell surface markers CD45R0, CD62L and CD197 (CCR7), the CD4+ and CD8+T lymphocytes were divided into central (Tcm) and effector memory cells (Tem), naïve T lymphocytes (Tnaïve) and terminally differentiated effector cells (Temra) using flow cytometry technique. The proliferative activity of Tcm, Tem and Tnaïve was evaluated in response to PHA as a functional marker of T cells. We have found that the percentage of peripheral CD4+TemCD62L+ and CD8+TemCD62L+ cells in the patients with asthma exacerbation was significantly reduced, if compared to the donors. Following PHA stimulation, these differences in T cell subsets between the groups of patients and donors were not detectable. We performed a correlation analysis between the memory T cell contents and age of the subjects studied. It was shown that the relative amounts of CD4+ and CD8+ memory cells increased with age in asthmatics, but not in healthy donors. Analysis of mitogen-induced proliferation showed that Tcm and Tnaïve cells proliferated more actively than other subpopulations in both groups. Meanwhile, the proliferative activity of CD4+T lymphocytes and subsets of CD8+Tcm, CD4+Tcm and CD4+Tem62L was higher in the group of asthma patients in remission state than in the patients with exacerbating disease, and healthy donors. The revealed increase in the relative number of memory T cells with age suggests that these cells participate in development of bronchial asthma. Proliferative response of the studied subpopulations, which was comparable to the donor values, suggests a functional maintenance of memory T cells and naïve T lymphocytes in bronchial asthma. The increased proliferation of some T-cell subpopulations in asthmatics in remission suggests an activated state of memory T cells. The observed decrease in the number of CD4+TemCD62L+ and CD8+TemCD62L+ in patients with asthma exacerbation may be, by our opinion, associated with an active inflammatory process in the airways.

Purpose of the stydy. To study the Features of the technological component of the Ivanovo region health system policy in malignant tumors early diagnosisMaterials and methods. The base of the research is the Ivanovo Regional Oncology Dispensery, Department of Health of the Ivanovo Region. Methods: sociological, expert assessment, analytical, documentary. The assessment of the technological component of oncological service policy was carried out in the three areas: a) an assessment of the quality of oncological assistance using the method of correspondence examination of completed cases of assistance with filling out expert assessment cards (600 cases of assistance); b) an assessment of patients' satisfaction with the help provided by the method of a sociological questionnaire survey (600 patients); c) an assessment of the apparent patients' dissatisfaction with the help provided based on the analysis of justified complaints (30 people).Results. The expertize of oncological medical services provided showed that there is a decrease in a number of its properties in modern conditions. The first ranking places in terms of the frequency of violations belong to the following properties of medical services quality: timeliness; adequacy; continuity; performance, availability. In the structure of medical and organizational defects in the quality of care, according to the results of expert evaluation, the leading part of them- 70.5% — is occupied by diagnostic defects (non-compliance by the medical personnel with the oncological screening standard, non-use of instrumental and laboratory research methods).Conclusion. The policy of oncological care quality has signs of decrease (the number of diagnostic and medical-organi­zational defects averages 1.7 for each case of diagnosed cancer), which leads to advanced cases of oncopathology. The results of the study showed that the current system of oncological care in modern conditions is not sufficiently effective and requires improvement, including by increasing the doctors' level of cancer alertness, increasing the efficiency of the regional cancer pathology commissions.

Objective. The purpose of this study was to evaluate the length of telomeres in the arms of individual chromosomes in patients with bronchial asthma (BA).Materials and methods. The study included patients with BA (n = 10, the mean age (44 ± 8.2) years) and healthy donors (n = 10, the mean age (44 ± 8.4) years). Metaphase spreads obtained from peripheral blood mononuclear cells were used. At the time of sampling BA patients received treatment at the Clinic of Immunopathology, Novosibirsk. BA was diagnosed by physicians according to GINA-2016. For measurement of telomere length on individual chromosome arms we used quantitative fluorescent in situ hybridization with a PNA-probe specific for telomeres. We used inverted DAPI banding for chromosome identification (according to ISCN-2013). For each individual 5 metaphase cells were analyzed. We applied the newly developed MeTeLen software to estimate the telomere repeats quantity (http:// www.bionet.nsc.ru/en/development/application-development/development-of-a-computer/metelen.html) in metaphase images. For enhanced image analysis compared with the previously developed programs, we included estimation of background signal and correction of defects of the optical system.Results. Comparing of telomere length show, that telomeres in the certain chromosome arms (4q, 5q, 9p, 10 q, 11p, 13p, 15q, 18q, 19q) in BA are significantly shorter than in corresponding group of donors (p < 0.05, Mann – Whitney U-test). For both studied groups we also evaluated telomere sequences shortened and elongated relative to the average telomere length in the group (p < 0.05, Wilcoxon-signed-runk test). The following differences and similarities between the telomere profiles of patients and donors were determined: the telomere sequences 4p, 6q, 8p were elongated and 2q, 9q, 11p, 15q were shortened relative to the average telomere length in BA patients. Moreover, this telomere sequences did not differ from the average telomere length in the group of donors. At the same time, the telomere sequences 12p, 16p, 17p, 19p were significantly shorter, and 3p was longer than the average telomere length in both groups.Conclusions. We guess, that the observed significant shortening of telomere length on individual chromosome arms in BA, as compared to donors, is relevant in pathogenesis of this disorder. The revealed features of telomere profile of patients with BA may be a result of different telomere length maintenance mechanisms and may influence to the development of asthma that needs further study.

The article discusses the determining role of immunopathogenesis of the main diseases of the modern man (cancer, atherosclerosis, autoimmune, allergic and infectious diseases). In this regard, the concept of «immune paradigm» is introduced. There is evidence that any pathology is based on the classical immune response to the antigen, whether auto- or xenoantigen, with all stages of its development and parallel changes in the state of immune tolerance: its breakdown in cases of autoimmune and allergic diseases and atherosclerosis; its establishment in cases of cancer and infectious diseases. In the meantime, it is emphasized that the immunopathogenesis is based on insufficient or increased function of immunocompetent regulatory cells with suppressive activity. Here the concept of «immunosuppressive dominant» is introduced. Finally, we discuss the need for fundamental changes in treatment of these diseases, with a focus on molecular and cellular immunotherapy methods and development of integrated approaches to their application.

The aim of the study was to investigate the features of T-lymphocyte apoptosis induced by components of autologous apoptotic cultures in vitro in norm and rheumatoid arthritis in the context of «cellular neighborhood».Materials and methods. Subjects of the study were blood samples of patients with rheumatoid arthritis (RA) and healthy women of comparable age. Developed protocol allowed to differentially evaluate the parameters of proliferation, early and late stages of apoptosis in the «primary» (CFSE-) and «secondary» (CFSE+) induced apoptotic T-lymphocyte cultures. It was estimated the effect of cellular and humoral components of unstimulated, anti-CD3- and dexamethasone-stimulated cells under the conditions of overcrowding and depleted culture media on autologous lymphocytes, cultured under physiological conditions, in norm and RA.Results. Comparative qualitative analysis revealed the features of the processes of T-lymphocyte apoptosis in norm and pathology. Also, the parameters of early and late stages of apoptosis of a «primary» induced culture and «secondary» induced cells after transferring the cellular and humoral components of apoptotic cultures did not differ significantly either initially or during culturing in both investigated groups. But it was a significant increase in the amount of living T-cells in «primary»-induced unstimulated and dexamethasone-stimulated RA patients’ cultures compared to similar donors’ cultures.Conclusion. There was no difference between stimulated with anti-CD3 antibodies cells and the «secondary» induced cultures. Taking into account the absence of significant differences in the parameters of activation apoptosis, the increased number of living cells in RA patients’ cultures relative to donors’ is evidence of contribution of non-autonomous apoptosis effects to cellular homeostasis in RA.

Aim. The aim of this study was the investigation of the influence of humoral factors of homeostatic proliferation IL-7 and IL-15 on T-regulatory cells in healthy donors.Materials and methods. The study included 15 conditionally healthy donors. Phenotyping and evaluation of expression changes of transcription factor FoxP3 and the main functional molecules on T-regulatory cells such as PD-L1, CTLA-4 and HLA-DR during cultivation under IL-7, IL-15 and anti-CD3 stimulation combined with IL-2 were performed by flow cytometry. Also, we estimated proliferation intensity of T-regulatory cells in the course of cultivation.Results. We revealed that humoral factors of homeostatic proliferation can effectively support a pool of T-regulatory cells during cultivation by number and phenotype and can maintain expression of important molecules such as PD-L1 and HLA-DR on regulatory T-cell surface. In addition, our study showed that IL-7 and IL-15 can cause relatively low T-regulatory cells proliferation in comparison to CD4+- lymphocytes.Conclusion. The observed ability of homeostatic proliferation factors to maintain T-regulatory cells pool presumably can play an important role in lymphopenic conditions when the number of effector cells is decreased and the insufficiency of interleukin IL-2 is observed, which plays a primary role in the homeostasis of T-regulatory cells in normal conditions.

We have developed and tested a technique for constructing 3D models of the chest and thoracic cavity organs. Due to the obtained results, the mathematical model was successfully used in the development of classification of variants of placement of implantable auxiliary circulation systems, and also for building 3D models for other purposes. In particular, the patients were graded according to the variants of placing the children’s axial pump DON-3 inside the patient’s chest cavity. Based on the data, the first fitting of the DON-3 pump was performed on a patient aged 7 years.

The influence of various environmental factors indirectly, through the epigenetic mechanisms of regulation of gene expression, can lead to the activation of human endogenous retroviruses. The purpose of this study was to investigate the possibility of activation of the first class HERV-E λ 4-1 (ER λ 4-1) endogenous retrovirus as a result of exposure to UV radiation in vitro.Materials and methods. Blood mononuclear cells (MNCs) of conditionally healthy individuals in a concentration of 20 x 106/ml were exposed to UV irradiation for 5 minutes on an ultraviolet radiator at a wavelength of 340 nm and a radiation intensity of 50 W/m2 in vitro. After irradiation, the cell samples were cultured for 24 hours in a complete culture medium in a CO2 incubator. Then, in these cell culture samples the proliferative activity, based on the incorporation of tritium labeled thymidine, a viability, by the trypan blue staining, and ER-E λ 4-1 expression by the reverse transcriptase polymerase chain reaction method, were determined.The main results. UV irradiation of mononuclear cell cultures for 5 minutes did not leads to the changes in their viability and functional activity. The study of the of the env ER λ 4-1 gene expression frequency in the MNC of donor’s blood before and after the exposure to UV radiation revealed the differences in this index. Thus, before the exposure to UV radiation, the expression rate of env ER-λ 4-1 was 4.4% (2/45), whereas after the irradiation its expression was determined much more often 24% (11/45). Along with an increase in the expression frequency, an augmentation in the mRNA level of the env gene ER-λ 4-1 was also observed.Conclusion. Thus, the exposure to ultraviolet radiation with the intensity of 50 W/m2 for 5 minutes on blood mononuclear cells of conditionally healthy individuals in vitro leads to activation of the human endogenous retrovirus HERV-E λ 4-1: an increase of its expression frequency and the level of mRNA.

Defects in programmed death of peripheral blood lymphocytes may result into autotolerance and chronic persistence of inflammatory reaction in rheumatoid arthritis. According to recent data, apoptosis is not an autonomous process, i.e., an excessive accumulation of cells in conjunction with a depleted medium leads to cellular excess, thus causing effect of cells already committed to apoptosis upon surrounding cells, by morphogenetic damage due to mechanical forces. Such effects are called compensatory proliferation or apoptosis-induced proliferation. Extracellular vesicles (ectosomes and apoptotic bodies) also have a negative effect on cultured cells, triggering their programmed apoptotic death. In turn, apoptosis can also be controlled by neighboring cells in non-autonomous manner.We conducted studies that allowed us to optimize methods aimed at the initiation of apoptotic cell death and to investigate the effects of apoptotic environment upon autologous cells under physiological conditions. The selected conditions in combination with a fluorescent labeling of lymphocytes and subsequent separate flow cytometric analysis allowed us to evaluate parameters of early apoptosis in subpopulations of peripheral blood T-lymphocytes in rheumatoid arthritis. In vitro studies of cells from the patients with rheumatoid arthritis allowed us to reveal a pronounced readiness of primary (CFSE) and secondary (CFSE+)-induced T lymphocytes for early apoptosis after stimulation with anti-CD3 antibodies. It was observed both against initial level of apoptosis, and when compared to cells induced for apoptosis. The obtained data suggest that stimulation of T lymphocytes with antibodies against CD3, and, as a result, an in vitro rise in cell proliferation rate leading to increased levels of early apoptosis not only among the cells directly receiving a proliferative stimulus, but also to increased effect of cellular and humoral components from anti-CD3-stimulated cultures upon normally proliferating lymphocytes.The transfer of an autologous apoptotic “aCD3” and dexamethasone-stimulated cultures, which were initially induced under conditions of cell overcrowding and medium exhaustion, was shown to activate the process of early apoptosis among normally proliferating cells. Glucocorticoids are known to serve as agents of cell death induced by activation. At pharmacological concentrations, glucocorticoids and their synthetic analogues stimulate endonucleases in activated lymphocytes. These enzymes destroy DNA in the internucleosomal regions thus resulting into cell apoptosis. The results obtained in present study suggest an opportunity of an in vitro early-stage apoptosis induction in T lymphocytes from the patients with rheumatoid arthritis, by means of cells subjected to activation-induced apoptosis.

The study aimed at evaluating the predisposition for development of different variants of SLE based on an inflammatory response in intact mice.Materials and methods. Low-dose systemic inflammatory response was modeled by the administration of lipopolysaccharide (LPS) of E. coli (strain 111: B4) by intact B6D2F1 recipients in the dose of 10 ng/mouse or 1 μg / mouse. We evaluated the number of leukocytes, neutrophils, and lymphocytes in the blood, the index of neutrophils / lymphocytes (ratio N/L), and the level of free DNA (cf DNA cell free) in dynamics. The first day after LPS injection we induced SLE model: the female B6D2F1 mice were injected 60–70 x 106 spleen cells of the DBA / 2 parent mice twice with interval five days. Three months after the induction of the model, the level of protein in the urine was measured twice: the mice with proteinuria 3 mg/ml and more were assigned to the group SLEnephritis+, and mice with less than 3 mg/ml of protein in the urine were assigned to the group SLEnephritis–.Results. It was established that administration of LPS does not change the frequency of nephritis in mice. The retrospective analysis of the number of leukocytes, neutrophils, and lymphocytes does not allow the prediction of the development of nephritis. We observed a significant increase in the frequency and the absolute value of the N/L index at week 8 relative to 4 weeks four weeks before the appearance of proteinuria in the group of mice SLEnephritis+ in contrast to mice SLEnephritis– when LPS was administered at a dose of 10 ng/mouse. Mice SLEnephritis+ and SLEnephritis– show different kinetics of the inflammatory response by an increase in the N/L index every subsequent hour relative to the previous one when LPS was administered at a dose of 1 μg/mouse. The dynamics of the cfDNA level is similar to the kinetics of an index N/L in the group SLEnephritis+ and the SLEnephritis–. The data obtained indicate the possibility of using of the index N/L and cfDNA level as a parameter of inflammatory response in mice and prediction of the susceptibility the development of nephritis.

The use of neural network classification algorithms for solving the problem of receiving telegram-code structures is considered. The article provides comparison of the neural network classifiers analyzing the normalized input signal as well as the signal after the binary conversion. Various measures of the code distance in the space of informative features are considered. Recognition comparative results for the selected pair of symbols are given. On the basis of these results the code distance is determined, which ensures the minimum recognition error probability. The results obtained in the developed neural network classifier are compared with those obtained in correlation receivers operating in the signal time and frequency domains. The advantage of neural network algorithm is shown. The structure implementing the developed neural network classifier is provided. It is shown that the procedure for the classifier developing, k \ including selection of information signs and their amount, as well as code distance, is not of general nature and is to be performed for each set of recognizable symbols. It is stated that to generalize the received alphanumeric blocks it is necessary to use the second decision contour where current information on the reception and information on the duration of the observed symbol is supplied, which is the subject of further research.

Over the last decades mechanical circulation support has become one of the most effective treatment methods for patients with terminal heart failure. Unfortunately, in pediatrics this method is generally used on a short-term basis and includes, first of all, extracorporeal membranous oxygenation and left ventricular bypass by means of the extracorporeal centrifugal pumps. Nevertheless, using of these methods in children allowed considerably reducing mortality on the waiting list for heart transplant. Today, practically the only method of long term mechanical circulatory support in newborns and children at an early age being used is the system of paracorporeal artificial ventricles EXCOR, the usage of which results in larger problems of thrombosis. There is little clinical experience in using of the fully implanted systems developed for adults in older children. Therefore, as shown in the present review, the problem of creating long term circulatory support systems for newborns and younger children on the basis of the implanted pumps continues to be relevant.

Increasing amounts of literature data suggest the leading role of indoleamine 2,3-deoxygenase (IDO) enzyme in regulation of immunosuppressive mechanisms. IDO is produced, mostly, by dendritic cells, being induced, e.g., under IFNγ involvement. Its function is to provide catabolism of tryptophan, an essential amino acid. Any reduction of tryptophan levels in extracellular environment was shown to cause functional suppression of certain immune cells, and induction of T regulatory cells. Accumulation of different tryptophan catabolites may exacerbate the immunosuppressive status induced by increased IDO expression. It is assumed that the interactions between IDO, tryptophan and its catabolites largely determine a development of hypersuppressor state in tumor growth and a hypo- (or lack of) suppressor status in autoimmune and allergic diseases. This implies some novel tasks for the therapy, including a treatment aimed for reduction of the IDO activity since the latter is involved in suppressor cell induction during tumor growth. Respectively, stimulation of IDO activity may augment suppressor activity of the regulatory cells.

A plant reference material (RM) was developed, which was certified in the content of fluorine-ion (% wt) in the cement raw mixture (PRM - 1 CM). Its metrological characteristics were set on the basis of results ofpotentiometric, photometric and titrimetric methods of analysis. The substantiation of the need for RM is given to increase the accuracy of results when determining fluorine in materials of cement production. The conditions are defined to use X-ray fluorescence method for estimating the material homogeneity in developing similar RMs. The interpretation of the error in residual heterogeneity in the results of analysis of powder materials and calculations of a smallest mass of representative sample is given when analyzing of such materials.

In the review a comparative analysis of the treatment of end-stage chronic heart failure using heart transplantation and durable mechanical circulatory is conducted. It shows the main advantages and limitations of heart transplantation and the prospects of application of durable mechanical circulatory support technology. The main directions of this technology, including two-stage heart transplant (bridge to transplant – BTT), assisted circulation for myocardial recovery (bridge to recovery – BTR) and implantation of an auxiliary pump on a regular basis (destination therapy, DT).

Application of zymosan in medicine is limited because of its side effects, since the native granules of zymosan directly activate serum complement components and phagocytic cells. In this regard, it was decided at the outset (ex vivo) to incorporate the granules of zymosan in the neutrophils, and only then inject these "loaded" zymosan neutrophils into the bloodstream. Our experiments showed a total inhibition of the weight accretion of both tumor affected liver (from 5220 ± 963 to 1327 ± 219 mg) and spleen (from 328 ± 29 to 187 ± 64 mg) of mice. Thus these data showed that even on the 17th day after a single intravenous injection zymosan-treated neutrophils persist expressed manifestations of anti-tumor activity in the liver and spleen, that may be basis for using this method for antimetastatic preventive measures in liver and other localizations.

The authors described the variants of initial surgical d-bridement on the basis of experience of treatment of 183 patients of multistaged treatment program.

The issues of immune pathogenesis in autoimmune pathology are discussed in this review. The main attention is drawn to potential pathogenetic role of various suppressor cell populations, including T-regulatory cells, mesenchymal stem cells, myeloid lineage-derived suppressors. Homeostatic lymphocyte proliferation is considered to be of great importance for pathogenesis of autoimmune disorders. Recent data from literature suggest that the autoimmune diseases are characterized by reduced activity of the mentioned suppressor cell populations, thus being a possible prerequisite for development of autoaggressive clones of cytotoxic lymphocytes, increased synthesis of autoantibodies leading to evolving autoimmune pathology. It should be, however, noted, that all these processes are accompanied by changes in the immune system induced by homeostatic proliferation of lymphoid cells.

The aim of this study was to evaluate subpopulational profiles of Tand B-lymphocytes in the patients with chronic obstructive pulmonary disease (COPD) under the influence of a multivalent vaccine against Pseudomonas pathogens, in order to justify its usage as a potential immune stimulator of microbial origin. Sixty patients (39 males and 21 females aged 40 – 58 years old) with verified diagnosis of COPD II-III degree were included into the study group. All the patients received a standard COPD therapy. In accordance with planned treatment, this cohort was divided into two groups using a simple randomization. Group 1 included thirty COPD patients (20 men and 10 women) who received standard treatment. Group 2 consisted of thirty COPD patients (19 men and 11 women) who received treatment according to conventional schedule, but further, they were additionally treated with «Pseudovac» vaccine used as a infection-preventing measure. The «Pseudovac» vaccine was injected, according to appropriate instructions for the drug use. Immunological evaluation was performed three times: at admission, as well as 10 and 20 days of treatment. As a control group, 35 healthy individuals (19 men and 16 women) of a similar age range have been examined. Assessment of Tand Bcellspecific immune phenotypes was determined by means of flow cytometry using direct immunofluorescence of leukocytes whole peripheral blood using specific monoclonal antibodies. We have found that Tand Blymphocyte profiles in the COPD patients are characterized by decreased numbers of T-cells (due to drop in cytotoxic T-cells), and increased B-lymphocyte contents. Relative amounts of NKTand γδT-lymphocytes showed an increase in cases of developing bacterial infection. The T-lymphocyte subpopulations in patients with COPD are characterized by increase in relative numbers of regulatory T-cells, Th2-lymphocytes, and T-cells expressing activation markers. B-lymphocyte population in COPD patients was characterized by increased levels of B2-, B1and memory B-cells, along with reduced levels of CD23-receptor-positive B-lymphocytes. During a standard treatment of infectious and inflammatory disease in COPD patients, there is a tendency to normalization of Tand B-lymphocytes subpopulations. However, T lymphocyte number by the 20th day of treatment proved to be reduced (due to decrease in cytotoxic cells), whereas B-lymphocyte content was increased. Furthermore, the levels of NKTand T-regulatory cells remain high at the standard COPD treatment. The «Pseudovac» vaccine exerts a pronounced immunoactive effect upon adaptive immunity, by means of restoring and/or normalizing Tand B-lymphocyte subpopulations in COPD patients by the 20th day of vaccine treatment.