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Polarimetry provides information about physical characteristics of cometary dust. Here, the authors show that the polarization of interstellar comet 2I/Borisov exceeds the typical values for comets, and this together with its polarimetrically homogenous coma suggests a more pristine nature of the object.

Introduction. Presbyopia is a global problem affecting more than 1.5 billion people worldwide. Projections indicate an increase in the average age of the population to 40 years by 2050, which is associated with an increase in the presbyopia incidence and corresponding economic losses. Despite the widespread prevalence of presbyopia, there are currently no effective methods for early prevention and restoration of dynamic accommodation and a standardized approach to assessing age-related changes in the lens that underlie presbyopia. The purpose: to study the effect of age-related changes in the lens on accommodation and to consider modern pharmacological approaches to the prevention and treatment of presbyopia.Methods. A multicenter prospective study was conducted, including analysis of visual acuity, the nearest point of clear vision and the volume of accommodation in individuals aged 40 to 55 years. Study participants were prescribed pyrenoxine (Catalin) as eye drops three times daily for 4 months. The study included 382 questionnaires collected from 29 ophthalmologists.Results. As a result of the study, the average distance to the nearest point of clear vision decreased slightly, but the reserve of accommodation remained at the same level. This indicates the absence of significant progression of age-related decrease in the reserve of accommodation as one of the manifestations of presbyopia and the possible effectiveness of pyrenoxine in preserving the elastic properties of the lens.Conclusion. The study confirmed the effectiveness of pyrenoxine in the prevention of presbyopia and the preservation of accommodative abilities in middle-aged people. The concept of Dysfunctional Lens Syndrome may be useful for clinical practice by providing opportunities for early diagnosis and treatment of presbyopia. Incorporating this concept into clinical guidelines may improve approaches to the treatment and prevention of age-related lens changes.

The hadronic part of the electron structure function F2e has been measured for the first time, using e+e− data collected by the DELPHI experiment at LEP, at centre-of-mass energies of s=91.2–209.5 GeV. The data analysis is simpler than that of the measurement of the photon structure function. The electron structure function F2e data are compared to predictions of phenomenological models based on the photon structure function. It is shown that the contribution of large target photon virtualities is significant. The data presented can serve as a cross-check of the photon structure function F2γ analyses and help in refining existing parameterisations.

Immune relationships involved in a wide range of immunopathological conditions, including ankylosing spondylitis (AS), are formed due to the characteristics of the subset composition of follicular T helper cells (Tfh) and B lymphocytes. Expression of the HLA-B27 antigen can change the reactivity of cells of the immune system and, accordingly, their interaction and participation in the immunopathogenesis of AS. The aim of this study was to investigate the characteristics of the subset composition of Tfh and B cells in HLA-B27-positive and negative patients with AS. Material and methods. 66 patients (17 women and 49 men) aged 20–58 years with a diagnosis of AS were examined. Molecular genetic research on HLA-B27 expression was carried out using the quantitative PCR method with real-time detection. The subset composition of Tfh and B cells was studied using flow cytometry. Results. An increase in the amount of Tfh2 in the blood is observed in all patients with AS. The number of Tfh1 was reduced in HLA-B27-positive AS patients, but Tfh17 cell content was increased. Changes in the subset composition of B lymphocytes, which were found only in patients with an HLA-B27-positive form of the disease, manifest themselves primarily as an imbalance in the distribution of B cell memory. Only negative correlations of Tfh1 and Tfh17 content with “double-negative” B cell and plasmablast precursors percentage are detected in HLA-B27-negative AS patients. Tfh1 cell number correlate negatively with naïve and activated naïve B cell content in HLA-B27-positive disease, Tfh2 cell percentage – with memory B cell fraction number. CCR6+ Tfh and Tfh17 have positive regulatory effects on plasmablast precursors. Conclusions. The subset composition of Tfh characterizes the dominance in the immunopathogenesis of AS of the direction of the regulatory influence of follicular T helper cells on B lymphocytes regardless of the carriage of the HLA-B27 gene in AS patients. High levels of Tfh type 17 are also detected in HLA-B27-positive patients. The relationships between the subsets of Tfh and B cells in HLA-B27-negative AS patients characterize the presence of processes aimed at inhibiting B cells. The influence of Tfh1 is aimed at suppression of B-cell immunity in HLA-B27-positive AS while Tfh2 and Tfh17 stimulate B-cell mechanisms.

Introduction. While developing the algorithms for diagnosis and treatment of patients with thermal injury, an injury outcome prediction index with the best predictive properties should be used.Aim. To compare the predictive properties of the Revised Frank Index and other specialized indices.Material and methods. A retrospective observational study included 307 patients with thermal injury, of whom 80 (26%) died. We compared the discriminatory ability, as well as sensitivity, specificity, positive predictive value and negative predictive value, the accuracy of the diagnostic test in relation to predicting a fatal outcome for 8 specialized prediction indices: RFI, FI, Baux, RBS, PBI, ABSI, BOBI, and Ryan.Results. RFI showed the largest area under the ROC curve: 0.942 [0.913–0.971], other indices had a smaller area: FI 0.827 [0.768–0.886], Baux 0.860 [0.811–0.909], RBS 0.891 [0.848–0.933], PBI 0.893 [0.848–0.937], ABSI 0.838 [0.786–0.890], BOBI 0.865 [0.819–0.910], Ryan 0.816 [0.764–0.869]. The Ryan index had the highest sensitivity (95%), but its specificity (49%) was the lowest, and the proportion of false positive results was 60%. The RBS index had high sensitivity (84%) and specificity (80%), but the false positive rate was 40%. The RFI and PBI indices showed similar sensitivity (81%), however, the proportion of false positive results for RFI (23%) was lower than that of PBI (39%) and all other indices, and the RFI accuracy in predicting the outcome was the highest among the other indices, making 89%.Conclusion. The predictive properties of the Revised Frank Index are better than those of other specialized indices.

Aim. To study the functional activity of blood eosinophils in patients with Opisthorchis felineus (O. felineus) invasion.Material and methods. A total of 328 patients with O. felineus invasion (120 men and 208 women, mean age 40.3 years) and 34 practically healthy patients (14 men and 20 women, mean age 41.1 years) aged 18 to 70 years were examined. The main method for diagnosing opisthorchiasis was the determination of eggs or bodies of adult parasites in the duodenal contents and/or feces, which was used in all 328 patients with opisthorchiasis. All patients underwent a complete blood count and biochemical blood test, esophagogastroduodenoscopy and ultrasound examination of the abdominal organs. The study of the functional activity of blood eosinophils was carried out in 42 patients with opisthorchiasis and 34 healthy individuals from the control group by chemiluminescent analysis with the measurement of the intensity of production of reactive oxygen species in spontaneous and zymosan-induced reactions in lucigenin- and luminol-dependent processes.Results. The frequency of eosinophils in the complete blood count above 5% in the examined patients with opisthorchiasis was 19.5%. An increase in the content of eosinophils in the blood in patients with opisthorchiasis was associated with an increase in the frequency of complaints of pain in the right hypochondrium, pruritus, skin rashes, an increase in the proportion of leukopenia and neutropenia, an increase in the level of gamma-glutamyl transpeptidase in the blood, and an increase in the frequency of ultrasound signs of cholecystitis. At the same time, a pronounced increase in the functional activity of blood eosinophils, determined by the chemiluminescent method, was observed in patients with O. felineus invasion.Conclusions. Patients with O. felineus invasion with an increase in the content of eosinophils in the blood due to the likelihood of an aggressive course of the pathology deserve the close attention of practitioners with the need for a thorough comprehensive examination of patients, including immunological methods.

Elimination of the hepatitis C virus (HCV) due to direct antiviral drug (DAD) action affects alteration in virus phenotype and, accordingly, NK cell functional activity. However, the published data are very contradictory. The aim of the study was to investigae alterations in NK cell subset phenotype after DAD treatment of HCV genotype-dependent chronic viral hepatitis C (CVHC) patients. Materials and methods. 111 CVHC patients and 21 healthy volunteers were examined. The diagnosis was established on epidemiological, clinical and laboratory data. All 111 subjects with CVHC received direct antiviral drugs Sofosbuvir and Velpatasvir for 12 weeks. The study of the NK cell phenotypes wwas analyzed by multicolor flow cytometry. Results. A decreased count of cytokine-producing along with increased frequency of cytotoxic NK cells were found in CVHC patients blood samples with various HCV genotypes prior to DAD treatment. The imbalance of cytotoxic cells with a high level of functional activity was also found in CVHC patients regardless of HCV genotype. The patients with HCV genotypes 1 and 3 showed significantly increased level of immunoregulatory NK cells. In addition, increased count of glycohydrolase (CD38) and ecto-5'-nucleotidase (CD73)-expressing NK cells were found in patients with HCV genotypes 1 and 3. Hence, such alterations in NK cell phenotype in CVHC patients were presented as sustained high viral load which peaking at carriers of HCV genotype 1 that was minimal in patients with HCV genotype 2. The most prominent change in NK cells after DAD treatment was found in CVHC patients with HCV genotype 2 (normalization of CD8-expressing NK cell subset composition and count). Only patients with HCV genotype 2 after treatment had increased frequencies of peripheral blood double-negative CD38–CD73– NK cells. Patients with HCV genotypes 1 and 3 also showed minimally improved in NK cell subset composition after DAD treatment. Conclusion. Evaluation of specific changes in NK cell phenotype during DAD treatment of CVHC patients driven by HCV genotype undoubtedly is of importance and high relevance. The results obtained are novel and complement the insights into CVHC immunopathogenesis. Analysis of NK cell phenotypes and functional activity in patients with CVHC may promote development of new methods for treating HCV infection.

Abstract A combination of a high sediment input and intense bottom currents often leads to the formation of contourites (sediments deposited or significantly reworked by bottom currents). Both of these components are present in the Vema Fracture Zone valley which is the most important passageway for the distribution of the Antarctic Bottom Water from the West to the North-East of the Atlantic. However, no contourite drifts, moats or contourite channels have been found in this region in more than half a century of research. The prevailing sedimentation paradigm postulates that turbidity currents have predominantly governed sedimentation in this region during the Pleistocene. This work describes the first example of contourite depositional system identified in the Vema Fracture Zone. The discovery was made through detailed high-resolution sub-bottom profiling, as well as numerical modeling and direct measurements of bottom current velocities. Such systems are exceptionally uncommon in fracture zones. This study highlights the importance of further research of contourites along the Vema Fracture Zone based on modern concepts of contourite and mixed depositional systems. The work also emphasizes the need to reevaluate the impact of bottom currents on sedimentation in this region, and particularly in the narrow segments of the fracture zone valley.

The aim of our study was to investigate the main characteristics of peripheral blood NKT cell phenotype in patients with disseminated purulent peritonitis (DPP) in dynamics of postoperative period, depending on the disease outcome. Fifty-two patients with acute surgical diseases and injuries of the abdominal organs complicated by DPP, and 68 healthy individuals in control group, were examined. Blood sampling was performed before surgery (preoperative period), as well as on the day 7, 14 and 21 of postoperative period. All patients with DPP were divided into two groups depending on disease outcome in postoperative period: patients with favorable disease outcome (n = 34); and patients with unfavorable outcome (n = 18). Study of the phenotype of blood NKT lymphocytes was performed by flow cytometry using direct immunofluorescence of whole peripheral blood samples with monoclonal antibodies. The low relative and absolute level of NKT cells was observed in DPP patients regardless of outcome disease in preoperative period. At the same time, the absolute level of NKT cells returned to normal only in patients with favorable DPP outcome and only by day 21 after surgery. Patients with favorable DPP outcome by the end of examination period had normalized quantity of mature NKT-lymphocytes and significantly decreased level of cytotoxic cells which was apparently associated with migration of such cell subsets to site of inflammation. A reduced level of non-classical (expressing CD8 marker) mature and cytokine-producing NKT cells was detected only in patients with favorable DPP outcome in preoperative period which returned to normal by the end of postoperative period. At the same time, patients with unfavorable disease outcome had reduced quantity of NKT cells of these subsets by day 21 of postoperative treatment. Patients with favorable outcome had high level of mature and cytotoxic CD11b+ NKT cells already in the preoperative period, while patients with unfavorable DPP outcome had increased level of cytotoxic CD11b+ NKT cells only by day 21 after surgery. The proportion of NKT cells expressing activation markers (CD28 and CD57) was reduced in patients in preoperative period that returned to normal immediately after surgery with favorable outcome, while it recovered with unfavorable outcome closer to the end of postoperative examination. The defined features of NKT cell phenotype in patients with unfavorable DPP outcome characterize disturbances in subset ratio and mechanisms of functioning of this cell fraction. This determines a need to develop immunotherapeutic methods aimed at stimulating immunoregulatory activity of NKT cells.

The aim of the present study was to evaluate the subpopulation profile of T and B lymphocytes, and their relationships during therapy of the patients with Graves’ disease (GD) treated by means of radioactive iodine. We have examined 36 women with verified diagnosis of GD. The contents of thyroid hormones were determined by immunoradiometric analysis. The levels of thyroid-stimulating hormone receptor autoantibodies (rTSH) were evaluated by enzyme-linked immunosorbent assay. On the basis of comprehensive pre-therapeutic examination, all patients were exposed to the fixed-activity therapy with radioactive iodine-131 at a dose of 400 to 700 MBq administered orally in isotonic aqueous solution of sodium iodide. 56 practically healthy women were examined as a control group. The phenotype of T and B cells in whole blood was studied by flow cytometry using direct immunofluorescence. It was shown that the patients, prior to treatment with radioactive iodine, had high levels of cellular functional activity, as determined by expression of CD25 antigen on T cells and CD23-antigen on B lymphocytes. Higher functional activity of the cells responsive for adaptive immunity in the patients with GD manifests in the presence of increased levels of autoantibodies to rTSH. By means of correlation analysis, we found that the patients with GD examined before the therapy had the thyroid status may determine the functional stimulation of T and B cells, thus increasing the levels of autoimmune processes. One month after radioiodine therapy (RIT), the GD patients, along with transient hyperthyroidism with increased concentration of autoantibodies to rTSH, showed a reduction of activated T lymphocyte contents (including T helpers and cytotoxic T cells) to control values. However, the level of cytotoxic T lymphocytes in the blood remained low, and the content of Treg cells was significantly increased in the patients. Decreased contents of B cells activated memory B cell to the control levels were found in patients with GD over 1 month after RIT when studying the phenotype of blood B lymphocytes. In this case, increased levels of naive B lymphocytes and B2 cells were detected, as well as decreased numbers of activated B1 lymphocytes. The observed changes in the subpopulation composition of T and B cells, and in their phenotype developed against the background of complete absence of relationships between the studied parameters, thus suggesting loss of thyroid control of immune processes and cooperative cell interaction during the development of the immune response. Generally, the phenotypic changes of T and B lymphocyte subsets in the blood of patients with GD through 1 month after treatment with radioactive iodine may reflect a trend for decreased functional activity of adaptive cellular immunity which may also account for inhibition of autoimmune processes.

Introduction. There is a discussion about which genotype of viral hepatitis C (HCV) is the most aggressive. Some authors consider that the 1st genotype is the most aggressive, others define the 3rd HCV genotype as a factor that determines the high activity of the pathological process. The solution of this issue is important for optimizing the tactics of patient management.Aim. To compare the clinical and laboratory characteristics and the incidence of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes.Materials and methods. 297 patients with genotype 1 of HCV and 231 patients with genotype 3 of HCV were examined. The diagnosis of chronic viral hepatitis C was established according to the recommendations of the European Association for the Study of the Liver (2016, 2018). Liver fibrosis was studied by shear wave transient elastometry with METAVIR score.Results and discussion. The frequency of elevated ALT in the blood prevailed in patients with HCV genotype 3 compared with persons with HCV genotype 1 (90.5% vs. 82.8%, p = 0.02). ALT levels above 3 norms were registered in 29.0% of patients with genotype 3 and in 16.8% patients with HCV genotype 1 (p = 0.001). The frequency of liver fibrosis F2 according to METAVIR was 11.8% in patients with genotype 1 and 21.2% in patients with genotype 3 of HCV (p = 0.005); the frequency of liver fibrosis F3–F4 according to METAVIR was 20.5% in patients with genotype 1 and 32.5% in patients with genotype 3 of HCV (p = 0.003). The combination of high viral load and high inflammatory activity, which was associated with liver fibrosis F3–F4 according to METAVIR in both compared groups, was determined in 16.9% of patients with genotype 3 and only in 10.4% of patients with genotype 1 of HCV (p = 0.04).Conclusion. The obtained data allow us to consider that in the surveyed population the course of chronic viral hepatitis C with genotype 3 is clearly more aggressive than in persons with genotype 1 of HCV.

Objective: to construct geometric models of carotid bifurcation and build a computer modeling for carotid endarterectomy (CEA) operations with patches of various configurations.Materials and methods. The method uses reconstructed models of a healthy blood vessel obtained from a preoperative computed tomography (CT) study of the affected blood vessel of a particular patient. Flow in the vessel is simulated by computational fluid dynamics using data from the patient's ultrasonic Doppler velocimetry and CT angiography. Risk factors are assessed by hemodynamic indices at the vessel wall associated with Wall Shear Stress (WSS).Results. We used the proposed method to study the hemodynamic results of 10 virtual CEA operations with patches of various shapes on a reconstructed healthy artery of a particular patient. The reason for patch implantation was to ensure that the vessel lumen is not narrowed as a result of the surgery, since closing the incision without a patch can reduce the vessel lumen circumference by 4–5 mm, which adversely affects blood flow. On the other hand, too wide a patch creates aneurysmorphic deformation of the internal carotid artery (ICA) mouth, which is not optimal due to formation of a large recirculation zone. In this case, it was found that the implanted patch width of about 3 mm provides an optimal hemodynamic outcome. Deviations from this median value, both upward and downward, impair hemodynamics. The absence of a patch gives the worst of the results considered.Conclusion: The proposed computer modeling technique is able to provide a personalized patch selection for classical CEA with low risk of restenosis in the long-term follow-up.

The aim of current study was to compare profiles of T cell subsets in the patients with ankylosing spondylitis (AS) who received different modes of genetically engineered biological therapy (GEBT). The research involved 58 patients aged 20 to 58 years diagnosed with AS and treated with anti-TNFα and antiIL-17 drugs, as well as those receiving common anti-inflammatory therapy. The AS diagnostics was based on the modified New York criteria. Disease activity was assessed by means of nomenclature approved by the Assessment of Spondyloarthritis International Society and Outcome Measures in Rheumatology. 45 healthy people aged 18 to 57 were included into the control group. Peripheral blood T cell subsets were analysed by multicolor flow cytometry. It was found that the T lymphocyte subpopulation profiles in AS patients showed significant differences depending on the therapy type. First, T lymphocyte counts were decreased in AS patients receiving traditional anti-inflammatory therapy, whereas relative numbers of T cells with high levels of effector potential and cytokine secretion were increased. Negative correlations between the levels of effector memory and pre-effector cytotoxic T cells and other laboratory and clinical indexes of inflammatory activity in AS may reflect lower efficiency of traditional therapy. Next, the levels of main T cell subsets in AS patients during antiIL-17 therapy fully corresponded to the control values. However, based on numerous correlations between immunological and clinical laboratory parameters, it was concluded that anti-IL-17 therapy had an inhibitory effect on the joint inflammation activity, while the state of T cell subsets was mainly dependent on standard anti-inflammatory therapy. The most pronounced changes in T cell subsets were found in AS patients during anti-TNFα therapy was associated with decreased effector potential of Th cells and cytotoxic T lymphocytes. At the same time, the lowest frequency of extraskeletal manifestations was found in AS patients treated with anti-TNFα drugs. Finally, the higher efficiency of GEBT, compared with conventional methods of therapy, is determined by the effects upon immune targets of AS pathogenesis which manifested, e.g., by changes in the T lymphocyte subpopulation profile. Moreover, usage of anti-TNFα versus anti-IL-17 inhibitors was associated with greater effect upon phenotypic profile of T cells.

The article describes a computer modeling technique that allows predicting the development of restenosis of the internal carotid artery after carotid endarterectomy (CEE). A clinical case has been demonstrated that proves the effectiveness of the developed method. It is indicated that for the correct formation of the geometric model, data from multispiral computed tomography with angiography of the patient after CEE with a layer thickness of 0.6 mm and a current of 355 mA are required. To build a flow model, data of color duplex scanning in three sections are required: 1. In the proximal section of the common carotid artery (3 cm proximal to the bifurcation); 2. In the section of the external carotid artery, 2 cm distal to the carotid sinus; 3. In the section of the internal carotid artery, 2 cm distal to the carotid sinus. The result of computer calculations using specialized software (Sim Vascular, Python, Open Foam) is a mathematical model of blood flow in a vessel. It is an array of calculated data describing the speed and other characteristics of the flow at each point of the artery. Based on the analysis of RRT and TAWSS indicators, a computer model of bifurcation is formed, which makes it possible to predict areas of increased risk of restenosis development. Thus, the developed technique is able to identify a cohort of patients after CEE, subjected to a high probability of loss of the vessel lumen. Such an opportunity will provide a more precise supervision of these patients in the postoperative period with the aim of early diagnosis of restenosis and timely prevention of the development of adverse cardiovascular events.

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

Triazole fungicides are widely used in agricultural production for plant protection, including pea (Pisum sativum L.). The use of fungicides can negatively affect the legume-Rhizobium symbiosis. In this study, the effects of triazole fungicides Vintage and Titul Duo on nodule formation and, in particular, on nodule morphology, were studied. Both fungicides at the highest concentration decreased the nodule number and dry weight of the roots 20 days after inoculation. Transmission electron microscopy revealed the following ultrastructural changes in nodules: modifications in the cell walls (their clearing and thinning), thickening of the infection thread walls with the formation of outgrowths, accumulation of poly-β-hydroxybutyrates in bacteroids, expansion of the peribacteroid space, and fusion of symbiosomes. Fungicides Vintage and Titul Duo negatively affect the composition of cell walls, leading to a decrease in the activity of synthesis of cellulose microfibrils and an increase in the number of matrix polysaccharides of cell walls. The results obtained coincide well with the data of transcriptomic analysis, which revealed an increase in the expression levels of genes that control cell wall modification and defense reactions. The data obtained indicate the need for further research on the effects of pesticides on the legume-Rhizobium symbiosis in order to optimize their use.

Post-COVID syndrome develops in 10–20% of people who have recovered from COVID-19 and it is characterized by impaired function of the nervous, cardiovascular, and immune systems. Previously, it was found that patients who recovered from infection with the SARS-CoV-2 virus had a decrease in the number and functional activity of NK cells. The aim of the study was to assess the effectiveness of recombinant human IL-2 (rhIL-2) administered to correct NK cell phenotype and functional activity in patients with post-COVID syndrome. Patients were examined after 3 months for acute COVID-19 of varying severity. The phenotype of the peripheral blood NK cells was studied by flow cytometry. It was found that disturbances in the cell subset composition in patients with post-COVID syndrome were characterized by low levels of mature (p = 0.001) and cytotoxic NK cells (p = 0.013), with increased release of immature NK cells (p = 0.023). Functional deficiency of NK cells in post-COVID syndrome was characterized by lowered cytotoxic activity due to the decreased count of CD57+ (p = 0.001) and CD8+ (p < 0.001) NK cells. In the treatment of patients with post-COVID syndrome with recombinant IL-2, peripheral blood NK cell count and functional potential were restored. In general, the effectiveness of using rhIL-2 in treatment of post-COVID syndrome has been proven in patients with low levels of NK cells.

The aim of the present study was to analyze the relationships between expression of activation and adhesion receptors on peripheral blood neutrophils, and intracellular activity of some neutrophil enzymes in patients with kidney cancer (KC). Patients and methods: the KC patients (n = 72) (T3N0M0, clear-cell type) were examined prior to surgical treatment at the Krasnoyarsk Regional Oncology Center. The diagnosis was verified histologically for all KC patients. The phenotype of blood neutrophils was studied using flow cytometry. The surface receptor expression levels of the neutrophils were evaluated by mean fluorescence intensity. NAD and NADP-dependent dehydrogenases activities in purified peripheral blood neutrophils were measured by bioluminescent method. Results: we have found that the phenotypic alterations in circulating KC patients’ neutrophils appeared along with inhibition of main intracellular metabolic processes and were closely linked with them. The features of the phenotypic imbalance in the neutrophils from KC patients were associated with a decrease in blood cells expressing adhesive (CD11b and CD62L) and functional (CD64 and HLA-DR) receptors. Moreover, the patient’s neutrophils expressed CD11b, CD16 and HLA-DR on their cell surface more intensively, than neutrophilic leukocytes from control group. These phenotypic changes in KC patients’ blood neutrophils occurred in parallel with pronounced decrease in immature cells numbers. The metabolic changes of neutrophil cytoplasmic compartment in KC patients were determined by a decrease in Glu6PDH activity (a key and initializing enzyme of the pentose phosphate cycle) and NADH-LDH (anaerobic glycolysis). Mitochondrial metabolism in neutrophils of KC patients was characterized by multidirectional changes in the activity of NAD- and NADP-dependent glutamate dehydrogenases (decreased activity of NAD-dependent and increased activity of NADP-dependent) and a decrease in NADH-MDH activity. The established features in mitochondrial enzymes activities suggest some disturbances of NAD-dependent processes that could lead to down-regulation of aerobic energy processes. We guess that the decreased activity of plastic and energy processes in blood neutrophils of KC patients could affect the receptor expression levels. By means of correlation analysis, we have found that the relationships in KC patients were determined by negative effects of NADHGDH and NADH-LDH activities upon expression of activation and adhesion receptors in blood neutrophils. Of these enzymes, only glutathione reductase activity in neutrophils from KC patients was positively linked with the CD23 and HLA-DR expression. Thus, an increase in activity of energy processes (e.g., coupling the tricarboxylic acid cycle to amino acid metabolism) in blood neutrophils from the patients with kidney cancer could stimulate expression levels of activation and adhesion receptors and potentially increase antitumor activity of neutrophils.

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.

Introduction. Diseases of the liver and biliary tract are a significant problem in the clinic of internal diseases. Opistorchiasis is one of the most frequent causes of this pathology and is one of the most widespread parasitoses in the Russian Federation.Clinical course of this pathology is characterized by high frequency of allergic and skin symptoms. Treatment of such patients is a big problem.Aim. To determine the effectiveness of the use of complex therapy with the inclusion of enterosorbent in patients with opisthorchiasis with skin syndrome.Materials and methods. The study involved 92 patients with chronic opisthorchiasis, of which 38 patients were with skin syndrome and 54 individuals without skin manifestations. Diagnosis of opisthorchiasis was carried out by two methods: microscopic examination of duodenal bile and coprooscopy. All patients underwent clinical examination, a clinical and biochemical blood analysis, esophagogastroduodenoscopy, ultrasound of the abdominal organs and liver elastometry with fibrosis assessment using the METAVIR system. Skin syndrome was diagnosed by dermatologist. After etiological treatment, 38 patients with opisthorchiasis with skin syndrome underwent reconstructive pathogenetic therapy for 6 weeks, which included an antispasmodic, ursodeoxycholic acid, desensitizing drug, and enterosorbent.Results. In patients with opisthorchiasis with a skin syndrome, the severity of clinical and laboratory manifestations was significantly higher than in individuals with parasitosis without skin syndrome. Reconstructive pathogenetic therapy of patients with opisthorchiasis with the inclusion of enterosorbent Polysorb has allowed to achieve a significant improvement in the condition of patients. Conclusion. From our point of view, the results obtained make it possible to raise the question of changing the treatment standards for patients with opisthorchiasis with skin syndrome.

The article considers the option of organizing joint processing of radar information in a multistatic rangefinder - doppler radar system. The least-squares method is used to obtain analytical expressions for oblique ranges and radial velocities of targets during joint processing of range-finding measurements of various types. The obtained expressions for inclined ranges have some similarities with the secondary processing of radar information, with the only difference being that the weighting coefficients for the evaluated parameters are updated in the case of successive measurements as data are received, and in the case of joint processing, they depend on the number of positions and the number of measurements. It is shown that the joint processing of measurements of the inclined range, the sum of the distances, the radial velocity and the rate of change of the total range allows to increase the accuracy of measuring the location of an air object and the projections of its velocity vector on the axis of a rectangular coordinate system. The physical basis for increasing the accuracy of positioning is to use redundant measurements by processing the total ranges. The considered option of processing redundant measurements in a multistatic radar system does not require time to accumulate data, and the task of increasing accuracy is solved in one measurement cycle. The potential accuracy of determining the location of an air object for different values of the standard errors of the determination of rangefinding parameters in a multistatic radar system at various distances between positions has been calculated. For an arbitrary trajectory of an air object, simulation-statistical modeling was performed, which allows to obtain the mean square errors of determining the location and velocity vector of the air object. A gain is shown in the accuracy of determining the location and velocity vector of an air object in comparison with traditional algorithms for determining coordinates in long-range multistatic radar systems.

Aclinical case ofprimary immunodeficiency state (PIDS) is described: X-linked agammaglobulinemia in the boy of 8 years old. The results of molecular genetic studies: gene btk (ex 1-19) genome version GRCh38.p5, transcript version ENST00000308731 single nucleotide substitution identified с.1027С > Т in homozygous state leading to premature stop codon p.Gln343Ter (p.Q343*). The presented clinical case reflects the low alertness of pediatricians for PIDS. At the same time, a delay in diagnosis and prescription of treatment aggravates the prognosis of the disease course and reduces the quality of the patient life.

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.

Th cells may exhibit pathological activity depending on the regulatory and functional signals sensed under a wide range of immunopathological conditions, including ankylosing spondylitis (AS). The relationship between Th cells and cytokines is important for diagnoses and for determining treatment. Accordingly, the aim of this study was to investigate the relationship between Th-cell subset composition and serum cytokine profile for patients with activity-driven AS. In our study, patients were divided into two groups according to disease activity: low-activity AS (ASDAS-CRP < 2.1) and high-activity AS (ASDAS-CRP > 2.1). The peripheral blood Th cell subset composition was studied by flow cytometry. Using multiplex analysis, serum cytokine levels were quantified and investigated. It was found that only patients with high-activity AS had reduced central memory (CM) Th1 cells (p = 0.035) but elevated numbers of CM (p = 0.014) and effector memory (EM) Th2 cells (p < 0.001). However, no activity-driven change in the Th17 cell subset composition was observed in AS patients. Moreover, low-AS activity patients had increased numbers of Tfh17 EM cells (p < 0.001), whereas high-AS activity was associated with elevated Tfh2 EM level (p = 0.031). The serum cytokine profiles in AS patients demonstrated that cues stimulating cellular immunity were increased, but patients with high-AS activity reveled increased IL-5 level (p = 0.017). Analyzing the data obtained from AS patients allowed us to conclude that Th cell subset differentiation was mainly affected during the CM stage and characterized the IL-23/IL-17 regulatory axis, whereas increased humoral immunity was observed in the high-AS activity group.

Introduction. The urgency of the problem of opistorchiasis is dictated by the long clinical course of the disease with the possibility of formation of hepatobiliary pathology, including cancer. Aim. To study the peculiarities of the production of active oxygen forms of blood phagocytes in patients with opistorchiasis. Material and methods. A total of 42 patients with chronic opisthorchiasis (22 men and 20 women) and 35 apparently healthy patients (18 men and 17 women) between the ages of 24 and 45 were examined. Opistorchiasis was diagnosed by three methods: microscopic examination of duodenal bile, coproovoscopy and serological method. The control group was composed of healthy individuals who underwent routine medical examinations, which included biochemical blood tests, identification of markers for viral hepatitis and antibodies to opistorchs. The culture of neutrophils and blood monocytes was isolated by fractionation of cells on the ficoll with subsequent cleaning from adhering cells. Functional activity of neutrophils and blood monocytes was estimated by chemiluminescence method on production of active oxygen species: basic and after induction with zymosan. Results. In patients with opistorchiasis in comparison with healthy people, in neutrophil granulocytes, the maximum intensity of active oxygen species production decreased and the time to reach the maximum of active oxygen species production was increased both in spontaneous and zymosan-induced reactions in luminoland lucigenin-dependent processes. In monocytes during spontaneous reaction study it was discovered that the maximum intensity of oxygen production in luminoland lucigenindependent processes decreased and the time of reaching the maximum of oxygen production in luminol-dependent process increased in opistorchiasis patients in comparison with healthy people. When studying the zymosan-induced reaction in monocytes, a decrease in the maximum intensity of active oxygen species production in both reactions and an increase in the time to reach the maximum output of active oxygen species in the luminol-dependent process was registered in patients with opistorchiasis in comparison with healthy people. Conclusion. The data obtained indicate low functional activity of blood phagocytes in patients with chronic opistorchiasis in comparison with healthy people.

The aim of the study was to investigate an interdependence between the phenotype of dendritic cells (DC) differentiated from monocytes and the number of pro-inflammatory monocytes in peripheral blood of patients with kidney cancer (KC). The study involved 28 patients at the age of 40-55 years suffering with KC (Т3N0М0, clear cell type) before surgical treatment. The diagnosis was verified histologically. 31 healthy agematched persons were examined as a control group. Mononuclear cells were isolated from heparinized venous blood by centrifugation in a Histopaque®-1077 density gradient followed by plastic adsorption in RPMI 1640 medium supplied with 10% autologous serum. Immature DCs (iDCs) were generated from blood monocytes by culturing for 5 days with GM-CSF and IFNα. Activation of DCs (mDCs) was induced by incubation with the tumor cell lysate and TNFα, followed by incubation for 48 hours. A tumor fragment was used to prepare the lysate of autologous tumor cells. Phenotyping of blood monocytes and DC at various maturation stages was performed by flow cytometry. The numbers of CD14+CD16+ monocytes in peripheral blood of KC patients were decreased (up to 42% of the total monocyte level) against the control ranges. In this regard, the analysis of the dependence between the phenotype of DCs differentiated from monocytes and the number of pro-inflammatory blood monocytes was carried out by comparing the groups with a high content of pro-inflammatory monocytes in the blood in KC patients (> 42%, near-control range) and low content (resp., < 42%). We have found that the contents of tolerogenic iDC in cell culture are increased in KC patients with low amounts of pro-inflammatory monocytes in blood (< 42%). A relatively increased expression of antigen-presenting and co-stimulatory molecules proved to be the specific feature of iDC phenotype in patients with high contents (> 42%) of proinflammatory monocytes in blood. The phenotype of dendritic cells in KC patients with different content of proinflammatory monocytes during maturation/activation showed more differences. In the patients with low levels of pro-inflammatory monocytes, the cell pool of in vitro maturing DCs was characterized by low level of CD86 and HLA-DR receptor expression, thus reflecting a weak co-stimulating and antigen-presenting activity. In the patients with high levels of pro-inflammatory monocytes in blood, the in vitro activated DCs showed higher level of functional activity using the above markers. The revealed differences in the DC phenotype and interrelations with amounts of blood monocyte subpopulations in KC patients may presume the programmed cell differentiation mechanisms depending on the microenvironment, under pathogenic conditions (i.e., in presence of malignant tumor growth).

The article presents the current state of hyperhydration issue in burn patients as a result of excess volume of infusion therapy during the acute period of burn disease. We report the data on the pathogenesis of burn disease and standard formulas for determining the volume of infusion therapy in case of burn shock, mechanisms and clinical manifestations of hyperhydration in burn patients and modern methods of its management. Since the danger of hyperhydration persists even after a shock in an acute period of burn disease, a method is proposed for determining the baseline volume of infusion therapy in the post-shock period. The developed algorithm is effective for prevention of hyperhydration in burn patients and covered by an invention patent.

The aim of the study was to investigate a dependence of respiratory burst state in neutrophils on activities of their intracellular enzymes in patients with acute destructive pancreatitis (ADP) of different severity. The study included 50 patients with ADP of moderate (17 cases) and severe degree (33 cases). A group of 47 healthy people was examined as controls. The respiratory burst state was examined in neutrophilic granulocytes by means of chemiluminescence assays. A study of NAD(P)-dependent dehydrogenases activity in blood neutrophils was performed using bioluminescent analysis. We have revealed that a decrease in spontaneous and induced synthesis of superoxide radical by neutrophils was detected in ADP patients, independently of the disease severity. Kinetics of primary ROS synthesis was also impaired in patients with severe ADP. In patients with moderate disorder, the level of secondary ROS synthesis by neutrophils proved to be increased, whereas, in cases of severe disease, a disturbed kinetics of secondary ROS synthesis by neutrophils was detected at a resting state, showing increased synthetic level upon additional induction by zymosan. Metabolism of neutrophils in patients with ADP is characterized by activation of plastic processes (due to the products of the pentose phosphate cycle) and aerobic energy (increased substrate flow intensity in the cycle of tricarboxylic acids). However, NADPH neutrophilic pool in patients with moderate disorder could be additionally supported by enzymatic malic enzyme reactions and NADP-dependent glutamate dehydrogenase. Activation of peroxidation events in patients with severe ADP is revealed, which needs NADPH compensation. The state of energy processes in blood neutrophils in patients with ADP is characterized by lacking changes in glycolytic activity, and increased intensity of substrate flux along tricarboxylic acids cycle. Activity of aerobic processes in patients with moderate disease is maintained by the products of amino acid metabolism (via glutamate dehydrogenase), whereas, in severe ADP it may be provided by products of lipid catabolism. Using correlation analysis, a dependence of respiratory burst of neutrophils on the state of their metabolism was studied. We have found that intensity and kinetics of respiratory burst in the neutrophils of controls depends only on the activity of NADP-dependent dehydrogenases. The changes in cellular metabolic activity in the patients with moderate ADP led to disturbances of their regulatory effect upon the state of neutrophil respiratory burst. In patients with severe disorder, the degree a neutrophil respiratory burst is stimulated by reductive amination of α-ketoglutarate, being, however, inhibited by intracellular peroxidation processes.

Currently, in areas of large cities there is a steady trend towards an increase in the spatial density of telecommunications systems. Saturation of the radio spectrum with analogue and digital systems used to solve problems of radio communication and television allows on their basis improving the technologies for semi-active radar detecting and determining the coordinates of air objects. The introduction of radar surveillance using transmitters not intended for radar purpose is often called a semi-active radar using outside or “parasitic” emission sources. The advantages of the systems are the minimization of the deployment costs, low operational energy costs, a low probability of establishing distortions, stealth operation, environmental friendliness and lack of requirements for radio frequency resource allocation. The relatively large elevations of the antennas of communication and television transmitters with the existing emitted power create favorable conditions for the detection of low altitude air objects. The digital signals of modern telecommunications systems have a spectrum width that provides acceptable resolution and accuracy for measuring the full range and angular coordinates. In general, a system of this type is a poly-static (multi-static) system consisting of one or more radiation sources and one or more receiving positions scattered in space. The promising task such systems solve along with airspace control is air traffic control. The article considers options for determining the rectangular coordinates of air objects in a system of bistatic radar stations using radio emission from external sources for target detection. The variants of the location of air objects with different composition of primary measurements of coordinates and a number of transmitting positions are considered. Analytical expressions are given for calculating the projections of the target velocity vector on the axis of the Cartesian coordinate system. The accuracy of airborne positioning for multi-static radar systems of this type is estimated.

The aim of present study was to investigate relationships between indicators of functional activity of neutrophilic granulocytes, and hemostasis parameters in patients with acute destructive pancreatitis (ADP). The study included thirty-three patients with ADP. 35 healthy persons were examined as a control group. The phagocytosis level in neutrophils was determined by flow cytometry using FITC-labeled staphylococcal protein A. We have calculated the percentage of fluorescent neutrophils as phagocytic index, and average cell fluorescence assumed phagocytic number. The intensity of respiratory burst observed in neutrophil samples was evaluated using chemiluminescence assay. All the persons under study were also tested for blood coagulation and vascular-platelet hemostasis. It was found that the ADP patients with decreased number of phagocytic neutrophils in the blood showed a decrease in respiratory burst intensity in the neutrophils. Moreover, spontaneous and induced synthesis of the primary reactive oxygen species (ROS) in neutrophils of ADP patients proceeded faster than in healthy people, but its intensity was much lower. The maximal level of spontaneous and induced synthesis of secondary ROS in neutrophils of patients was significantly higher than in healthy individuals, but its rapid may be generally characterized by insufficient respiratory burst in these patients. A reduced neutrophil phagocytic activity and kinetic characteristics of primary and secondary ROS synthesis may be attributed to the effects produced by pancreatic enzymes entering blood flow which may alter functional activity of the blood neutrophils. Concerning hemostasis in patients with ADP, some disturbances were found only in the coagulation link which seem to depend on increase in fibrinogen, soluble fibrin monomer complexes and D-dimer in blood plasma, along with reduced antithrombin III levels. Such a change in blood coagulation indexes is typical to inflammatory processes and presumes activation of the coagulation cascade and higher risk of septic complications. In patients with ADP, we have found a significantly increased number of correlations between indicators of functional activity of neutrophils and hemostasis parameters. This analysis revealed a relationship by the patients with ADP reflect some unidirectional changes in functional activity of neutrophils (as phagocytosis and respiratory burst), and blood coagulation parameters (as blood clotting and vascular/ platelet links). The changes in functional activity of neutrophils and the state of hemostasis in the ADP patients, as well as correlations between their alterations are omvolved into the pathogenesis of this disorder, and determine potential mechanisms for evolving complications.

The aim of this work was a comparative study of the helper- (Th cells) and regulatory T cells (Treg) effects upon the phenotypic composition of B lymphocytes in blood and thyroid tissue in Graves’ disease (GD). 43 women with GD were examined. The diagnosis of GD was based on clinical and laboratory signs of the disease: complaints, clinical picture of the thyrotoxicosis with objective examination, characteristic sonographic changes in thyroid gland, as well as elevated titers of antibodies to thyroid-stimulating hormone receptor in blood serum, and corresponding changes in thyroid status. 67 practically healthy women were examined as a control. The studies of Th cells, Treg and B lymphocytes phenotypes in blood and thyroid tissue were carried out by flow cytometry using direct immunofluorescence, respectively, in whole peripheral blood and lymphocytes isolated from thyroid tissue. The relative amounts of Tregs in thyroid gland from the patients with GD corresponds to their level in the blood. We did not find any changes in the content of blood T helpers expressing vs. non-expressing CD25 receptors, as compared to the control values. In patients with GD, an increased B1 cells content was revealed in peripheral blood. The percentage of this B cell subpopulation in thyroid tissue is reduced when compared to the levels found in blood, but with increased memory B cells contents. The number of activated B lymphocytes (by CD23 marker) in blood of patients with GD is reduced when compared to control values. It was found that, in thyroid tissue, there is an even more pronounced decrease in the relative amount of activated B cells compared to the levels detected in blood from these patients. By means of correlation analysis, it was found that increase in activated B lymphocytes in blood from controls is accompanied by a co-directional reaction from Treg (the usual immunoregulatory process). In Graves’ disease, such a relationship was not found. The amounts of Treg and activated T helper cells in blood of the patients did positively correlate with common B lymphocytes, B2 cells and na ve B lymphocytes. Meanwhile, Treg’s in thyroid tissue, were completely excluded from the system of interactions with activated B lymphocytes. It is assumed that a decrease in Treg’s content in peripheral blood, along with altered functional activity is observed in patients with GD.

The aim of the study was to investigate the phenotypic features of dendritic cell (DCs) differentiated from peripheral blood monocytes in patients with kidney cancer (KC). The study involved 28 patients with KC (Т3N0М0, clear cell type) before surgical treatment at the age of 40-55 years and 31 healthy age-matched people. Immature DCs (IDCs) were generated from blood monocytes by culturing for 5 days with GM-CSF and IFNα. Activation of the DCs (MDCs) was induced by incubation with tumor cell lysate and TNFα followed by incubation for 48 hours. Phenotyping of DCs at different maturity degrees was carried out by the method of flow cytometry. It was found that the monocytes differentiated into IDCs formed a cellular pool with a high level of costimulatory activity in patients with KC, by increasing number of cells with a high level of CD80 and CD86 receptor expression. In this case, a significant amount of undifferentiated monocytes and cells with an intermediate phenotype (CD14+CD83+) remained in the cell culture. In KC patients, the cell culture formed an increased number of IDCs with the CD83+CD80highCD86highHLA-DR+ phenotype (in comparison with the control values). However, expression level of the HLA-DR receptor on CD83+CD80highCD86high-IDCs in patients with KC was reduced. Therefore, this type of DCs has a high costimulatory and weak antigen-presenting activity. Maturation (activation) of DCs from patients with KC was accompanied by retained amounts of undifferentiated monocytes in cell culture associated with decreased contents of cells with CD14+CD83+ phenotype. Presumably, a part of cells with the CD14+CD83+ phenotype and additional antigenic and cytokine load matured to the level of MDCs. Mature DCs in patients with KC are characterized by weak costimulatory and antigen presenting activity, due to decreased expression of CD83 and CD86 markers. Upon maturation, the amount of DCs with different levels of CD80 expression in cell culture in healthy people and in patients with RP is equalized, but the MDCs with a highly active phenotype (CD83+CD80highCD86high и CD83+CD80highCD86highHLA-DR+) are formed with KC cells to lesser degree. Moreover, MDCs with CD83+CD80highCD86high phenotype in tumor patients show weaker expression of receptors providing costimulatory and antigen-presenting activity. The differences in the IDCs and MDCs phenotype between healthy people and KC patients may be determined by different features of phenotype and functional activity in blood monocyte populations as well as immunosuppressive factors synthesized by the tumor.

Cytotoxic T lymphocytes (CD3+CD8+, Tcyt) play a major role in protective immunity against intracellular pathogens and can eradicate malignant cells. As based on CD45RA and CD62L expression, the peripheral CD3+CD8+ blood lymphocytes were divided into "na ve" (N) cells, central memory (CM) and effector memory (EM), as well as "terminally-differentiated" CD45RA-positive effector cells (TEMRA). Using multicolor flow cytometry, a co-expression of effector (perforin, granzyme B and CD57) and regulatory (CD27, CD28, CD244 (2B4), CD279 (PD-1) and KLRG1) molecules was studied on all these subsets. CD57 was expressed in 2.39±0.31% “na ve” and 5.45±0.91% of central memory Tcyt. Meanwhile, within EM and TEMRA Tcyt subset, its expression was identified on the cell membranes of 26.53±2.20% and 51.43±2.55% of cells, respectively. Cytolytic effector molecules (granzyme B and perforin) were detected in cytoplasmic granules of 4.22±0.36% and 5.30±0.43% of na ve Tcyt, respectively. For CM cells, these values were 10.09±1.17% and 24.90±3.10%, respectively. Dramatic increases of granzyme B and perforin expression were observed in the “EM → TEMRA” cell lineage, when the relative number of granzyme B-positive cells increased to 41.05±2.63% and 66.73±3.29%, respectively, while perforin was detected in 59.33±4.26% and 75.08±3.12% of cells, respectively. For regulatory molecules, CD244 and KLRG1, the similar dynamics were observed, their expression increased from “na ve” to late maturation stages, while the expression of two main costimulatory molecules – CD27 and CD28, decreased in the lineage N → CM → EM → TEMRA cells. The highest level of CD279 was observed in EM cells. It was shown that CD57-positive cells contain perforin and granzyme B in their cytoplasmic granules and lack CD28 expression. Furthermore, CD57 can be used as a surrogate marker for multicolor immunophenotyping to identify most mature effector cells containing cytolytic enzymes. Our results on the co-expression of all the beforementioned molecules suggest that the most mature CD45RA+CD62L– effector peripheral blood cytotoxic T cells express CD244 and CD57, lack costimulation molecules CD27 and of CD28, as well as inhibitory receptors KLRG1 and CD279.

The aim of this study was to evaluate some features of subpopulational profile and functional activity of monocytes in patients with acute pancreatitis. The study included 33 subjects with acute pancreatitis of middle-to-severe degree. Thirty-five healthy age-matched people served as a control group. The study of monocyte phenotype was performed by flow cytometry. Phagocytic ability of monocytes was determined by flow cytometry, by means of FITC-labeled staphylococcal protein A. We assessed percentage of fluorescent monocytes (defined as phagocytic index), like as average cell fluorescence (phagocytic number). The phagocytic indexes were determined for a total monocyte fraction, and well as for distinct cell subpopulations (CD14+CD16- , CD14dimCD16+ и CD14lowCD16+). Intensity of respiratory burst in the monocytes was evauated with chemiluminescence analysis. We used two indicators (lucigenin and luminol) to assess production of primary and secondary reactive oxygen species. In the patients with acute pancreatitis, we have found certain changes in blood monocyte subpopulations and their functional activity. The changes in monocyte subpopulations in acute pancreatitis were characterized by increased numbers of inflammatory cell forms in blood (CD14lowCD16+), along with while near-normal contents of the cells with «classic» (CD14+CD16- ) and «non-classical» phenotype (CD14dimCD16+), having been within reference ranges. It is assumed that high levels of pro-inflammatory monocytes may produce a pathogenetic «circuit» which is characterized by positive mutual stimulation of monocyte-mediated inflammation in local (pancreatic) and blood compartments. Apparent development of such mutual induction of inflammatory events may determine a low efficiency of anti-inflammatory therapy in acute pancreatitis. The functional characteristics of the monocytes in patients with acute pancreatitis are defined as a decrease in phagocytic activity and low respiratory burst intensity. Reduced phagocytic activity of monocytes was detectable in all the cellular subpopulations. Decreased intensity of monocytic respiratory burst in acute pancreatitis depends on low background and induced synthesis of both primary and secondary reactive oxygen species. Thus the patients with acute pancreatitis exhibit imbalanced with respect to synthesis of primary and secondary reactive oxygen species in the monocytes may result from specific action of circulating pancreatic enzymes upon the cells, or due to increased concentrations of pro-inflammatory cytokines. The imbalance between the monocyte subpopulations and reduction of their functional activity in acute pancreatitis may represent an immunopathogenetic basis for development of pancreatic necrosis and sepsis.

The aim of this study was to investigate phenotypic profile of B lymphocytes in peripheral blood of the patients with chronic endometritis and adnexitis. The study involved 89 women in their reproductive age (18 to 45 years) with chronic endometritis (48 cases) and adnexitis (41 cases). Ninety-eight healthy agematched women participated as a control group. Phenotypic B-cell subpopulations were analyzed by flow cytometry performed with direct immunofluorescent staining of peripheral cells from whole blood using the following antibody panel: CD5-FITC/CD23-PE/CD19-ECD/CD45-PC5/CD27-PC7. A significantly reduced B-lymphocyte content was revealed in peripheral blood of women with chronic endometritis and adnexitis. The reduced cell numbers occurred due to reduced B2 (main fraction of B-lymphocytes) and as B1 cells (minor fraction) which determines insufficient reactivity of specific humoral immune response, including immune reactions at the mucous membranes. However, percentage of B2-lymphocytes was decreased only in endometriosis, whereas patients with adnexitis showed decrease in both relative and absolute counts of this B cell subpopulation. A decreased content of naive B-cells in the peripheral blood is another feature of the B cell phenotypic profile in chronic endometritis and adnexitis. Moreover, the drop of the naive B-cell levels in patients with adnexitis proved to be more pronounced than in persons with endometritis. Expression of CD23- antigen (a low-affinity receptor for IgE) has been investigated as a functional marker of B cells. All the studied peripheral B cell subpopulations expressing CD23 were decreased in the patients with chronic endometritis. The numbers of different B cell fractions expressing CD23 antigen were also reduced in the women with chronic adnexitis as compared to the levels detected in patients with chronic endometritis. Alterations of the B-cell immunity were more pronounced in chronic adnexitis, due to more extensive infectious/inflammatory process which involved both endometrium, and appendages, and clinical manifestation of the disease. The results suggest a need for evaluation of the B cell phenotypic profiles as a marker of inadequate immune response in infectious and inflammatory diseases of pelvic organs, as well as planning rational immunotherapy, in order to enhance therapeutic efficiency in these disorders.

The aim of this study was to evaluate correlations between cytokine concentrations and parameters of respiratory burst in blood neutrophils, in order to predict potential development of abdominal sepsis in the patients with extended purulent peritonitis (EPP). The study involved fifteen patients with EPP. Peripheral blood samples were taken on the first day post-admissiona. Abdominal sepsis was diagnosed in thirty-five patients (70%) within 5…10 days after surgical intervention. Clinical complications were absent in fifteen patients (30%). Sixty-seven healthy individuals were examined as a control group. Evaluation of the cytokine concentrations was performed by ELISA technique. The degree of respiratory burst in blood neutrophils was measured by means of chemiluminescence assay.It is revealed that the EPP patients exhibited increased levels of serum proinflammatory cytokines and IFNγ, along with higher intensity of respiratory burst in blood neutrophils, due to activated synthesis of of both primary and secondary reactive oxygen species (ROS). The EPP patients who later developed abdominal sepsis showed reduced spontaneous synthesis of primary ROS and increased spontaneous synthesis of secondary ROS. Upon zymosan induction of neutrophils, both primary and secondary ROS levels proved to be similar in the EPP subgroups with or without subsequent sepsis. EPP patients with uncomplicated post-surgical period still exhibited a predominant regulation of respiratory burst of neutrophils by IFNγ activity. Meanwhile, the neutrophil respiratory burst was correlated with TNFα and IL-6 in those patients who further developed abdominal sepsis. A stimulatory effect of IFNγ and a presumably inhibitory action of TNFα and IL-6 upon respiratory burst of blood neutrophils in EPP patients are associated with a release of large cytokine amounts during acute immune inflammatory events, and migration of activated cells to the inflammatory focus. In particular, the changes in the cytokine levels regulating the respiratory burst of neutrophils may be an important factor which predicts development of abdominal sepsis in EPP.