Vol 19, No 1S (2019)

“The natural healing force within each one of us is the greatest force in getting well.” Hippocrates Prof. G.F. Solomon was one of the first scientists to hypothesize that the relationship between brain activity and the body’s immune system can be important for determining health and influencing the course of the disease and its outcome. John Solomon is the founder of psychoneuroimmunology, an interdisciplinary field of research into the interaction of the brain, behavior, and immune system that has played a key role in the study of behavioral and biological mechanisms that link psychosocial factors, health, and disease. His research helped to found a new area of knowledge - psychoneuroimmunology, which aims to uncover the mechanisms by which the brain is able to influence the functions of the immune system.

Introduction. There is increasing evidence that altered neuroimmune responses are implicated in the neurobiology of aggression, including the production of pro- and anti-inflammatory cytokines. However, little is known about brain cytokine changes and their regional characteristics in animals genetically selected for either high or low aggressive behaviors. Materials and methods. In the present study the content of cytokines (IL-1β, IL-2, IL-6, TNFα, IL-10) was measured by ELISA method in the brain structures (the hypothalamus, striatum, frontal cortex, and hippocampus) in two rat lines selected for differences in fear-induced aggression at 2, 4, and 24 h after a peripheral injection of saline or lipopolysaccharide (LPS, 250 µg/kg). Results and discussions. LPS stimulation elevated cytokine activity above baseline levels in both aggressive and nonaggressive rats, but the pattern, time course of cytokine changes, and their regional characteristics varied according to the aggressiveness of the animals. After LPS administration, aggressive rats showed increased levels of IL-1β in the hypothalamus at 2 and 4 h and in the frontal cortex at 4 and 24 h compared to LPS-treated nonaggressive line. IL-2 was increased in the frontal cortex and striatum of aggressive rats within 24 h, while IL-6 elevation in the hypothalamus was found at 4 h and in the frontal cortex at 2 and 4 h. In the hippocampus, the levels of IL-1β, IL-2, and IL-6 were lower in LPS-treated aggressive rats than in nonaggressive animals. The levels of anti-inflammatory cytokine IL-10 were also decreased in all brain structures of aggressive rats receiving LPS. Conclusion. The present data indicate that genetic predisposition to increased aggressiveness is associated with region-specific changes in the content of pro- and anti-inflammatory cytokines and their variations over time in the brain structures.

The aim. Detect the relationship between sympathetic activity, secretory alpha-amylase (sAA) indices and mediators of the immune system in healthy young volunteers (18-20 years) with correction drinking behavior (use pure water of 35 ml/(kg body weight)). Materials and methods. A randomized, placebo-controlled double-blind study, which was carried out in 3 stages (09/20/2014; 08/11/2014; 12/13/2014) into 3 groups (test, placebo and control). The material used was saliva, in which IL-1β, IL-4, IL-6 were detected by ELISA and the activity of alpha-amylase (sAA) was determined colorimetrically on an automatic analyzer; the level of sympathicotonia was determined by calculating the Kerdo-index. Results. A decrease in the activity of sAA test and placebo groups to the second stage, and the preservation of this trend in these groups by the end of the study, in contrast to the increase in its activity in the control group. The ratio of IL-1β/IL-6 at the third stage (MCC, p = 0.048) in the test and placebo groups (146.66 and 111.61, respectively) exceeded (by 3 times and 2.4 times respectively) this indicator control group. In a subpopulation with a predictor of inflammatory diseases (PID) of the oral cavity (IL-1β ≥ 212 pg/ml) of the experimental group, the average IL-1β decreased to the third stage by 27% (from 247.7 pg/ml to 194.4 pg/ml), in the placebo group, a similar decrease was 31.5% (from 243.24 pg/ml to 184.96 pg/ml), while in the control the level of IL-1β remained at the same level (about 250 pg/ml), p > 0.05. By the end of the research, the Kerdo index showed a predominance in the test group of participants with parasympathicotonia (66.67%), while in the placebo group this figure was 58.33%, and in the control 50%. Conclusion. The obtained data suggest an immunomodulatory effect of the use of 35 ml/(kg body weight) of pure water (clean by the physical method) against a decrease in sympathicotonia.

It was previously known that the plasmalogens (Pls) are reduced in the Alzheimer’s disease (AD) brains. The clinical study showed that the oral intake of sPls (Pls extracted from the scallop) improved the cognition among mild AD patients. To examine whether Pls regulate memory processes, we reduced the Pls in murine brain hippocampus by shRNA against Gnpat (shGNPAT) and observed a significant reduction of spatial memory. This evidence suggest that Pls have an important role in the hippocampal dependent memory. This was further supported by our recent findings that Pls drinking for three months in adult B6 mice improved spatial memory by enhancing the BDNF-TrkB signaling which was associated with an increased expression of synaptic related gene expression. The Pls treatments increased the dendritic spines in the cultured neuronal cells and also in the murine brain. Our research findings indicate that Pls regulate the spatial memory in mice by regulating the gene expression related to memory processes. Our results may suggest that Pls drinking may also increase the memory related gene expression in the AD patients to improve the cognitive function.

Introduction. It is known that the systemic level of the major pro-inflammatory cytokine increases in many respiratory diseases such as asthma, COPD and sleep apnea [1, 2]. The lung ventilation changes and the pathological types of breathing are typical in these diseases. By the reason, the research of the respiratory effects of cytokine is actual. The aim of this study was to compare the respiratory effects of tumor necrosis factor - α (TNF-α) before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Materials and methods. Тhe experiments were performed in tracheostomized anaesthetized with urethane rats. A respiratory flow head connected to a pneumotachometer (AD Instruments ML141 Spirometer, Dunedin, New Zealand) was used to measure peak airflow and respiratory rate. The hypoxic ventilatory response was measured by using rebreathing with hypoxic gas mixture before and after the tail vein injection of TNF-α (10 μg/rat). In order to determine the role of the cyclooxygenase pathway in the ventilatory effects of TNF-α, introperitoneal administration of diclofenac, a nonspecific COX inhibitor, was used (0.5 mg/rat). Results and discussion. We have shown that the increase in level of TNF-α in blood increased the parameters of respiration such as minute ventilation (by 40%), tidal volume (by 18%), and the mean inspiratory flow (by 33%). The slope of the hypoxic ventilatory response decreased from 6.06 ± 0.91 to 3.48 ± 0.38 ml/min-1 mmHg-1 (by 40%) 40 min after administration of TNF-α (p < 0.05), the slope of tidal volume and mean inspiratory flow also decreased (by 27%) (p < 0.05). After pretreatment with diclofenac, the influence of TNF-α on breathing was dampened, as no significant changes were observed. Conclusion. We concluded that the elevation of inflammatory cytokine level in blood intensifies ventilation during the resting breathing that may be associated with increased central inspiratory activity. At the same time TNF-α reduces the chemoreflex sensitivity to hypoxia, thereby worsening the compensatory capabilities of the respiratory system. Thus, the results of our study suggest participation of inflammatory cytokines in mechanisms of central breathing control and chemoreception. Diclofenac pretreatment eliminated the respiratory effects of TNF-α. The data indicate that the ability of TNF-α to enhance basal ventilation and to reduce the ventilatory hypoxic response is mediated by the COX pathway.

Cytokine system and cartilaginous tissue metabolism of 27 women affected by 0-1 stage of primary and 19 women affected by 0-1 stage of post-traumatic osteoarthritis (OA) have been studied as well as of 10 healthy persons of the control group. The enzyme-linked immunoassay method was used to determine the content of cartilage oligometric matrix protein (СOMP), cartilage glucoprotein (YKL-40), interleukins (ILs) 4 and 1β in blood serum, collagen fragments (CTX II) in urine. It was found that СOMP, CTX II, YKL-40 and IL-1β concentrations grew at more intensive rate in case of primary OA compared to post-traumatic OA. The diminution of correlation relationship strength in IL-1β serum concentrations is noted with the system level of cartilaginous tissue degradation products on the background of YKL-40 regulatory influence buildup which is more prominent with primary OA than it is with the post-traumatic one. Conclusions: early stages of primary OA are characterized by more prominent degenerative changes in the joint hyaline cartilage due to losses of type II collagen and hyperproduction of proinflammatory link cytokines with the background of YKL-40 regulatory influence buildup and reduction of the IL-1β influence. The changes of cartilaginous tissue metabolism with post-traumatic OA were characterized by preservation of dependence on IL-1β serum concentration with the background of reduction of YKL-40 influence.

Objective. We studied mast cells and neuroendocrine cells of the skin of adults in the area of the acupuncture points (AP) and outside them. Material and methods. Using the Unna method (polychrome toluidine blue dye), mast cells were detected in the skin. Conducted immunohistochemical study using monoclonal antibodies to neuron-specific enolase and synaptophysin in order to identify neuroendocrine cells. Research results. Analyzed data on the distribution of mast cells in the skin in the area of the acupuncture points in an adult. It was revealed that the distribution of mast cells in the dermis and the hypodermis differs depending on the localization of the acupuncture point. Fat cells take in maintaining homeostasis and regulation of metabolism in the skin. NSE- and synaptophysin-positive cells were detected in the basal layer of the epidermis, in the area of the the muscles that raise the hair, in the area of the hair follicles; in the secretory terminal regions of the sweat glands, as well as outwards from the basement membrane of these regions between the myoepithelial cells. A part of the neuroendocrine cells is in contact with nerve waves. Expression of NSE and synaptophysin depends on AP localization. In AP of the skin of the abdomen and upper limb, a more pronounced expression of NSE and synaptophysin is observed than at the acupuncture points of the skin of the face. The expression of NSE in the structures of the skin in the area of the acupuncture points is more pronounced than the expression of synaptophysin. In the dermis revealed structureless spaces surrounded by mast cells, nerve fibers, blood vessels.

With systemic inflammation, hypoxia, and an increase in the respiratory, a significant increase in the systemic level of pro-inflammatory cytokines is observed. Recently we demonstrated that elevated IL-1β level in blood reduces the ventilatory response to hypoxia. The aim of the present study was to examine the hypothesis that the respiratory effect of IL-1β may be mediating the NO-dependent mechanisms.The experiments were performed on anaesthetized rats. We studied the effects of intravenous administration of cytokine during inhibition of iNO-synthase. In order to we used aminoguanidine bicarbonate - specific inhibitor of iNOS, which was injected in the tail vein for 30 minutes before the administration of cytokine. During the hypoxic rebreathing experiments, was found that the increase of IL-1β level in blood weakens the respiratory response to hypoxia. The ventilatory, tidal volume and mean inspiratory flow responses decreased by 29%, 31% and 53% respectively. INO-synthase inhibitor pretreatment eliminated these respiratory effects of IL-1β. Thus the data indicate that the ability of IL-1β to reduce the ventilatory hypoxic response is mediated by the NO-dependent pathway.

Neuroendocrine tumors (NET) is a heterogeneous group of epithelial neoplasms that develop from cells of the diffuse endocrine system and found in any organ. A distinctive feature of NET is the ability to produce various biologically active peptides and amines. Currently, the most useful markers are the universal marker chromogranin-A (CgA) and specific markers serotonin and 5-hydroxyindolylacetic acid (5-HIAA). The analysis of the clinical significance of the biochemical markers of NETs was carried out by comparative analysis of their levels in serum and urine of 339 NET patients and 66 healthy people. Determination of plasma CgA, serotonin in serum and 5-HIAA in daily urine was performed using standardized ELISA methods using the Chromogranin A ELISA kit (Dako), Serotonin ELISA and 5-HIAA ELISA (IBL) test-systems. The values of CgA, serotonin, 5-HIAA in patients with NET were significantly (p < 0.001) higher than the corresponding control values. Assessment of the diagnostic significance of CgA, taking into account the cut-off level 33 U/l (with a specificity of 98.5%), showed high sensitivity in the general NET group - 80.9%. The serial determination of the marker reflected the effect of treatment. The progression free survival in different treatment regimens for patients with NET has been associated with basal levels of CgA. The medians of serotonin and 5-HIAA levels were maximal in patients with carcinoid syndrome, significantly exceeding the corresponding values in NET patients without clinical manifestations.The data indicate the possibility of using CgA, serotonin and 5-HIAA to improve the accuracy of diagnosis, evaluation of generalization and biological activity of NETs.

The aim of the research was studying the features of neurohumoral regulation of carbohydrate metabolism in experimental diabetes mellitus. A model of diabetes mellitus was created by introducing 0.1% solution of epinephrine hydrochloride into animals. Biochemical parameters of carbohydrate metabolism (cortisol, C-peptide and glucose) were studied in 17 animals on day 0, 15, 21, 30, 45. On the same day morphofunctional changes formed in the pancreas and Nodi lymphatici pancreaticoduodenales were studied. With stress, there is an increase in cortisol and C-peptide and a decrease in the concentration of glucose in the blood. In distress cortisol secretion is reduced, and the production of C-peptide and glucose concentration in the blood increases. In the lymph nodes formed functional changes that led to a violation of cellular and humoral immunity in the body. Conclusion. The cause of diabetes is a failure in the work of self-regulating mechanisms of carbohydrate metabolism, which leads to dysregulation pathology of the autonomic nervous system, manifested by antagonism between adrenaline and cortisol, insulin and cortisol.

The aim of this study was to determine the amplitude-frequency characteristics of the electroencephalogram (EEG) and heart rate variability (HRV) in humans, depending on the initial serum TNF-α level at a single session of heart rate variability biofeedback (HRV BF) due to increase the total power of the HRV spectrum. Among hypertensive individuals (blood pressure 140-160/80-100 mm Hg) subgroups with an optimal serum TNF-α level (below than 75 quartile - 84,4 pg/ml) and with a high serum TNF-α level (more than 84,4 pg/ml) were selected. In individuals with an optimal serum level of TNF-α, an increase in the total HRV spectral power, a decrease in the stress index, systolic blood pressure and a decrease in the EEG power in the theta range in the frontal brain regions after HRV BF session were identified. In individuals with a high serum TNF-α level the effectiveness of HRV BF was minimal against the background of continuing sympathicotonia and high theta EEG-activity.

The aim of the work was to compare proteasome mechanisms of the development of donor-specific tolerance (DST) to ovarian allograft in outbred Wistar rats and inbred August rats with the increased level of monoamines and stress limiting systems in the brain. In spite of DST induction in all animals, engraftment was more effective in Wistar rats. In the liver of all rats with survived allograft, the level of proteasome immune subunt LMP2, evaluated by Western blotting, was significantly higher than in control false-operated rats. This difference was more pronounced in Wistar rats. Besides, in the liver of all rats with survived allografts, the level of proteasome PA28αβ activator was higher than in control. In conclusion, the development of DST is connected with the enrichment of liver proteasome pool by immune forms containing LMP2 subunit and PA28αβ activator. This process is partially suppressed in August rats under stress conditions of the central nervous system.

The epithelium of the respiratory tract of mammalian lungs contains pulmonary neuroendocrine cells, represented by both single cells and innervated clusters forming neuroepithelial bodies (NEB). Since NEB are intensively innervated and produce highly specific biologically active substances, such as the bronchoconstrictor serotonin, the level of which increases during hypoxia, it is assumed that these structures can play a key role in the pathogenesis of bronchial asthma (BA).The purpose of this study was to the detection and analysis of NEB in the lungs with experimental BA.For the study, we used the lungs of sexually mature Wistar rats (n = 5). NEB was detected by monoclonal antibodies to synaptophysine.It has been found but that in the context of experimental asthma 76.6% NEB were located as part of a simple cuboidal epithelium of small bronchi and respiratory bronchioles. 17.6% of NEB were found in the composition of the epithelial layer and only 5.8% are single NEB in the composition of the epithelium of the small bronchi. At the same time, a greater number of NEB localized in the bronchi were composed of 6 cells (46.2%), 38.5% of 4 cells, and 15.3% of more than 10 cells in one cluster. As in our previous studies, most of the NEB were located in the vicinity of the synaptophysi-immunopositive terminals. Against the background of asthma occurred reduction in the number of large clusters NEB and increased concentrations of medium size of NEB. The results obtained indicate the effect of inflammation on the functional features of the neuroendocrine system of the lungs and the possible contribution of NEB to the inflammatory cascade in BA.

Purpose: to study bone marrow mast cells in mice after autotransplantation. Materials and methods. Mast cells and sulphatedness degree of heparin mucopolysaccharide in the bone marrow were identified using Unna staining with polychromatic toluidine blue. Study results. Data on mast cells distribution in the bone marrow after autotransplantation in 40 minutes and in 2 hours were analyzed. Two types of mast cells’ reaction to autologous bone marrow introduction were identified: sequential degranulation and exocytosis. As a result, secretion of mast cells causes production of biologically active substances in the microenvironment of a mast cell; these substances form chains and conglomerates from granules, changes in the number of which can contribute to changing the process of mitotic division. According to morphological criteria three populations of mast cells were identified: small-sized cells, with blue-colored nuclei stained orthochromatically and located asymmetrically; metachromatic oval-shaped cells with a nucleus located in the centre; large, degranulated, gamma-metachromatic mast cells. Most part of mast cells in bone marrow smears is presented by integral forms. Heparin in mast cells takes part in regulating metabolism in the bone marrow after autotransplantation.

Efficiency of interval hypoxic training in treatment of hypothyroidism with autoimmune genesis in children and adolescents was shown. The therapeutic effect of hypoxic therapy realized not only through amplification of compensatory mechanisms for the oxygen delivery to the tissues, but also through inhibition of humoral immune responses and the stimulation of T-cell immunity in patients with autoimmune thyroiditis. Increase of function and quantity of CD8+-cells after a course of hypoxic therapy prevents the progression of the autoimmune process and helps to restore the function of the thyroid gland, which in turn leads to positive changes in the neurological status of patients: improved mental performance indicators and fine motor coordination. Complications of therapy or deterioration of the patients were not observed. Follow-up monitoring of patients conducted after 6-8 months after treatment showed that the positive effect of hypoxic therapy maintained throughout this period. Positive hormonal and immunological and neurological dynamics in children and adolescents with autoimmune thyroiditis after the interval hypoxic training suggests its inclusion in the scheme of pathogenetic treatment of patients with this pathology.

Objective: to study the clinical and immunologica features of the manifestation of chronic pain in systemic lupus erythematosus (SLE) patients with neurological symptoms.Methods. We examined 30 healthy individuals and 38 patients with SLE. Beck’s depression questionnaire was used to assess the presence of depressive symptoms. Antibodies to adenosine deaminase (anti-ADA), β2-glycoprotein-I-dependent antibodies to phospholipids of the IgG class (anti-FL) and antibodies to double-stranded DNA (anti-dsDNA) were determined in the serum of patients with SLE. Doppler sonography of the brachiocephalic arteries was performed for all patients with SLE.Results. Complaints about the presence of headaches of varying severity presented 35 people (92.1%). Migraine was recorded in 63.2% patients with SLE. Doppler ultrasound in patients with SLE with chronic headaches in 66.7% of cases showed signs of reduced blood flow in the arteries of the vertebrobasilar basin, which may indicate chronic brain ischemia. Signs of depressive disorder of varying severity were found in 36.8% of patients with SLE, and in patients with neurological disorders, moderate (p = 0.027) and severe (p = 0.041) depression were more often detected. Elevated levels of anti-ADA were found in 36.8%, and anti-FL in 44.7% of patients with SLE. It was noted that “migraine-like” manifestations of chronic pain syndrome were more common in the group of patients with SLE, who had a combined increase in anti-ADA and anti-FL (χ2 = 4.5; p = 0.024). Since a certain part of ADA is concentrated in the plasma membranes of vascular and platelet endothelium cells, it can be assumed that there is a conformational effect of anti-ADA on the β2-glycoprotein-I, leading to increased synthesis of anti-FL and undesirable activation of coagulation cascade in vessels.Conclusion. The combination of severe chronic headache with high levels of anti-ADA and anti-FL can precede the development of stroke and transient ischemic attacks, which emphasizes the need for additional immunological examination of patients with SLE with neurological symptoms.

The article presents the results of a comprehensive analysis of the parameters of innate and adaptive immunity in 85 patients with recurrent remitting multiple sclerosis (MS) with its exacerbation (54 people) and in conditions of persistent clinical remission (31 people). It is shown the signs of autoinflammation and increased reactivity of the T-link of adaptive immunity to be registered not only in exacerbation, but also in remission. The revealed changes determine the pathogenetic basis of MS progression and they should be taken into account when accompanying patients in remission to prevent clinical activation.

Impairments of immune system are an important mechanism of the degenerative dystrophic processes in the arthral tissues onset and development.The objective of this research was to study the cellular immunity condition in patients with osteoarthrosis before and after endoprosthesis implantation. The research methods included immunophenotyping of lymphocytes in the peripheral blood. The immunologic impairments before the surgery referred to change in T-cell immunity reflecting in the imbalance of immunoregulatory subpopulations (decrease of T-suppressor level and increase of T-helper content). At that the number of NK-cells rose which didn’t exclude a possible connection with the cartilage tissue degradation impurities on the background of B-cell number decrease. During the post-surgery period the decrease in T-helper and T-suppressor numbers was detected which may be related to their migration to implantation area due to the decrease of their number in the systemic circulation, at that no significant changes in T-lymphocytes were observed. By contrast, there was a decrease of NK-cell number at higher level of B-cell number showing an adequate response of the bodies for surgery aggression. The results of immunological research are worth being taken into account when preparing patients for endoprosthesis implantation surgery for the purpose of prescribing the immune-correcting drugs for pre-existing impairments of cellular immunity as well as in the post-surgery period to relieve the effects of surgical interference aggravating the impairments in this population of patients.

Bronchial asthma is a classic, antigen-specific disease, the formation of which is crucial reagin-dependent type of allergic reaction. However, the interaction of changes in the immune status and bioelectrical activity of the brain in patients with bronchial asthma is currently insufficiently covered. The paper analyzes the interdependence between changes in the immunological reactivity and bioelectric activity of the brain in patients with bronchial asthma. Changes in the immune state during bronchial asthma led to the development of hypoxia, which had a significant impact on the bioelectric potentials of the brain, manifested in the predominance of the alpha rhythm, left hemispheric dominance of alpha power in the anterior temporal leads.

The aim of the work was to study the factors of natural and adaptive immunity and systemic inflammation in subacute stage of schizophrenia to clarify the role of these systems in the chronization of the disease. 31 patients with the diagnosis of schizophrenia (SCI) with paranoid after 3-4 weeks of therapy were examined. The control group included 16 healthy volunteers. Markers of systemic inflammation and immunity, including key cytokines and lymphocyte subpopulations, were investigated. Increased levels of IgМ, C-reactive protein and cortisol in the blood were found in patients with SCI. Also in most cases the content of proinflammatory proteins IL-8, IL-6 and IL-10 was increased. The greatest increase in the levels of systemic inflammation and cytokines was found in patients with first psychotic episode. The content of HT was more often normal, but the level of NT-4 and nerve growth factor β (NGFβ) in most patients was positively associated with levels of IL-6. At low levels of BDNF a significant increase in levels of CIC, cortisol, IL-8, IL-6 and IL-10, but not Ig were found. Also, in patients with low BDNF symptoms of delusions prevailed, while in cases of normal or elevated BDNF (19 out of 24 cases), in addition to delusions, hallucinations were pronounced. Conclusion. It is believed that antipsychotic drugs reduce systemic inflammation and activity of the immune system. However, we have found signs of severe systemic inflammation, activation and dysfunction of the immune system in patients with SCI after 3-4 weeks of therapy. Preservation of immune disorders and systemic inflammation in patients with SCI despite clinical improvement can participate in the progression of the disease through neuroimmune interactions. Further studies of the trigger mechanisms of chronic immune activation are needed.

In the present study, an analysis of cognitive, behavioral, and metabolic changes during the dynamics of the development of pathology was conducted under an experimental model of chronic fatigue syndrome (CFS). A decrease in physical and research activity of experimental animals indicated the development of fatigue and a depressed emotional state. An increase in the concentration of lactate was also showed, that may indicate a violation of the energy metabolism.

In order to investigate the function of human endogenous retrovirus HERV-E λ 4-1 in multiple sclerosis pathogenesis, the comparative research of frequency of this retrovirus expression and mRNA level on different types of blood immune cells of progredient course multiple sclerosis patients have been conducted with using of the reverse - transcriptase polymerase chain reaction method. Peripheral blood mononuclear cells were isolated on Ficoll density gradient centrifugations. Monocytes were separated by the adhesion to plastic Petri dishes. For the estimation of the mitogen-induced HERV-E λ 4-1 expression, blood mononuclear cells were incubated with adding of phytogemagglutinin or pokeweed mitogen during 72 hours in CO2 incubator at 37 °C and 5% CO2. Results of HERV-E λ 4-1 env gene expression estimation demonstrate that both monocytes and lymphocytes express HERV-E λ 4-1. The level of the HERV-E λ 4-1 env mRNA was higher in lymphocytes than in monocytes. The main source of HERV-E λ 4-1 in progredient course MS patients between blood immune cells are lymphocytes, especially B lymphocytes.

Alzheimer’s disease (AD) is the most widespread neurodegenerative disease of older age, which is associated with the deposition of amyloid-beta polymerized peptide (consisting of 42 amino-acid residues) in the brain. The microglial phagocytosis disturbance, which is observed during AD, is possibly the key factor in the process. The research of neutrophils in patients with AD is of special interest due to the pressing problem of finding peripheral markers of AD. Analysis of neutrophils’ functional state in patients with AD is the objective of the present study. A reliable decrease of neutrophils’ phagocytic activity was established in group of patients with AD in comparison with control group (p < 0,05) (PI = 1.16 [0.64; 2.68] and PI = 2.34 [2.06; 2.85], respectively). A reliable increase of leukocytic elastase (LE) enzymatic activity (p < 0.05) was discovered in neutrophil lysate in AD group compared to control (LE = 0.43 [0.29; 0.77] and 0.29 [0.26; 0.38], respectively) at the same time. Comparison of PI and LE indicators in neutrophils’ lysate of AD group showed negative correlation between these parameters (r = 0.49, p < 0.05), which means that phagocytosis reduction during AD is accompanied by simultaneous LE activity increase in lysate of these cells.The obtained results allow to draw a conclusion that neutrophils’ phagocytic activity decreases during AD. Thus, discovered changes in neutrophils’ functional state can be considered as a potential peripheral AD marker.

The goal of this research was to study the clinical efficacy of course-based neurotrophic therapy in mild cognitive impairment (MCI) and the effect of therapy on immune parameters in patients, and to assess the prognostic value of the dynamics of immune parameters during the year after treatment. 20 patients with MCI receiving intravenous Cerebrolysin (20 infusions of 30 ml with increasing dose during the first four days) were examined. Neuropsychological and immunological examination was carried out immediately before the study, after 3 months., 6 months and after 1 year after the end of treatment. It was found that after therapy, patients had a long-term decrease in the severity of systemic inflammatory response, and that marked signs of systemic inflammation at the beginning of follow-up combined with a persistent decrease in the level of immunoglobulin G in dynamics were prognostic markers of MCI progression. In conclusion, it wass shown that neurotrophic therapy has a good clinical effect and has a favorable immunomodulatory effect in aMCI, and the relationship between the dynamics of humoral immunity and systemic inflammation and the risk of progression of cognitive impairment in patients within 1 year after therapy was established.

Inflamm-aging - the term, describes the development of chronic inflammation during aging without the infection pathology. It is supposed, that inflamm-aging is one of the reason of age-related pathology, partially, Alzheimer disease (AD). There were done comparative analysis of AD (Аβ42, τ-protein, р16) and inflammation (IL-6, TGFα, NF-kB) markers in hippocamp and blood lymphocytes in elderly and old people. It was shown, that expression of investigated signal molecules in hippocamp and lymphocytes of elderly and old AD people increased in comparison with people of control group (without neurodegenerative pathology). Thus, inflammation mediators play important role in AD pathogenesis and can be the potential target for neuropathology therapy.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. Previous findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. However how dysbiosis arises and whether this feature contributes to PD pathogenesis remains unknown. The aim was to evaluate gut microbiome and the serum cytokine profile in PD. We quantified serum interleukin (IL) levels (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) in 55 PD patients. Study of the fecal samples was performed by real time PCR method and bacteriologically. Discovered the relationship between the intensity of dysbiosis and the level of proinflammatory cytokine IFN-γ, IL-6.We show that disturbances in plasma cytokine level could be more profound in PD patients with altered composition of intestinal microbiota, which may explain the mechanism of influence of microbiota composition on the PD manifestations.

Currently, it is known that in response to brain damage a reaction from the immune system is triggered, but its role in the formation of clinical manifestations remains a little-studied problem to date. Using multicolor cytometric analysis, a study was conducted to determine the number of Th1-, Th2-, Tfh- and Th17-cells among CD45RA-negative CD3+CD4+ cells in a group of patients with mild TBI (M-TBI, n = 20) and with moderate to severe TBI (MS-TBI, n = 16) and a group of conditionally healthy donors (n = 30). The imbalance between Th2 cells and Th17 cells was found in patients with TBI in the acute period, which probably predetermines the course of the disease and the development of complications.

Stress loads in sport lead to the development of functional disorders of various body systems, including the digestive system. The use of pharmacological preparations for correction of dysbiotic states is very often. The aim of this work was to study the physical endurance of rats with dysbiosis with decreased and increased intestinal circadian rhythm (ICR) under conditions of emotional-physical stress. Dysbiosis with a decreased ICR was caused by the administration of loperamide (LPR) 2 mg/2 ml of physiological saline daily subcutaneously for 6 days. Dysbiosis with increased ICR was caused by the addition of lactitol (LT) 10 g to 200 ml of drinking water daily for 6 days. To model emotional-physical stress, a forced swimming test until exhaustion (drowning) with a load of 7% of the animal’s body weight and a water temperature of 14 °C was used. In the control group, the life span of rats was 136 ± 8 s. LPR increased the physical endurance of rats by 1.94 times compared with control. LT also had a positive effect, increasing the duration of forced swimming in 1.44 times compared with the control. The combined use of LPR and LT did not lead to a change in animal’s endurance. Thus, both types of dysbiosis can be considered as a variant of endogenous stress, which plays the role of adaptogenic factor that increases resistance to a stronger emotional-physical stress, leading to the increase in physical endurance of animals.

The involvement of olfactory dysfunction led to the proposal of ‘the olfactory vector hypothesis’ to explain both olfactory losses and the etiology of idiopathic Parkinson disease (PD) as a result of the transit of an environmental virus or chemical agent that enters the central nervous system (CNS) via the nose, activating the glial response of the brain that may lead to dopamine neuronal damage. Previously created chronic, progressive a mouse model of PD by intranasal instillation of a LPS displayed several key features of early-stage PD: a progressive hypokinesia, selective loss of dopamine neurons, a reduction in striatal dopamine content, and α-synuclein (α-syn) accumulation and aggregation in the substance nigra. Other PD model based on nasal inoculation with α-syn aggregates also expressed parkinsonian-like behavioral and immunological features.We suggested that intranasal administration of LPS might cause an increase in expression and misfolding of a-syn in olfactory receptor cells that are projected into olfactory bulbs. We observed an increase in the expression of the native and phosphorylated forms of immunoreactive a-syn in olfactory cells, olfactory nerve and olfactory bulbs where, in addition, activated glial cells were observed. The findings suggest that bacterial antigens can cause parkinsonian-like features both by inducing a glial neuroinflammatory response and by increasing the production of phosphorylated a-syn in peripheral structures of the olfactory system.

Prenatal stress is one of the major cause of long-term disorders in behavioral and neuroimmunne processes. Emotional prenatal maternal stress (PRMS) performsin an offspring tendency to anxiety, depressive-like behavior and weakening memorizing skills. The study field was to determinate preproorexin gene expression of the maturity rats held in prenatal stress on the 19th day. The expression level was measured in two hours after intravenous LPS injection. qPCR shoved significant reduction in preproorexin gene expression in hypothalamus cells. This result corresponds with behavioral tests where animals exposed to stress during the late term of in utero development demonstrate less motion search activity which allovers to suspect a connection between prenatal stress and incidences of psycho-neuro-immunne relationships disorders.

Various detrimental factors during early life may affect CNS development and increase risk of neuropsychiatric symptoms in later life. Disruption in brain dopaminergic system maturation is believed to be one of the mechanism of different neurodevelopmental disordrers. In this article we review behavioral peculiarities and changes of prefrontal D2 dopamine receptor splice variants (D2S and D2L) expression in rats after chronic experimental increase of proinflammatory cytokine interleukin(IL)-1β during 3rd week of life. Early life IL-1β treatment produce long lasting working memory deficit originating in juvenile adult animals. Elevation of IL-1β during 3rd week of life also affect developmental expression of D2 dopamine receptor mRNAs leading to increased D2S/D2L ratio in the medial prefrontal cortex of adolescent but not adult rats. Early life IL-1β treatment cancelled the learning-induced D2L mRNA downregulation during active avoidance conditioning in adult rats. Thus, dysregulation of expression of distinct D2 dopamine receptor splice variants within medial prefrontal cortex is supposed to be implicated in cognitive decline caused by early life immune challenge.

This study is devoted to diabetic polyneuropathy (DPN) - one of the common complications of diabetes mellitus (DM). The possibilities of laboratory diagnosis of this condition are shown. The purpose of this study was to examine the pathogenetic and diagnostic significance of certain neurospecific proteins and cytokines in DPN. The analysis of the literature data on the possibility of using neurospecific proteins and some cytokines in patients with diabetes as markers of neural tissue damage has been carried out.

Introduction. CXCL-13 can be involved in the development of MS, and its level in peripheral blood may have diagnostic and / or prognostic significance. The purpose of this study is to assess the level of CXCL-13 in serum and its relationship with the clinical and functional state of patients with remitting MS in remission. Materials and methods. The study involved 67 patients (28 men and 39 women) with a relapsing MS in remission. All patients were examined by scales and questionaries EDSS, Multiple Sclerosis Functional Composite, Multiple Sclerosis Impact Scale 29, Fatigue Severity Scale. On the day of the clinical examination venous blood samples were taken from patients and healthy donors, serum was isolated, and the level of CXCL-13 was assessed by enzyme immunoassay method. Results and discussion. It was revealed that CXCL-13 in the serum in patients with MS was significantly lower than in healthy volunteers. A relationship was found between serum CXCL-13 and the severity of neurological deficit according to EDSS, with walking speed of 25 feet, with an assessment of the quality of life and fatigue. Conclusions. Despite the association of CXCL-13 with the clinical and functional state of MS patients, at present time this chemokine cannot be considered to be a diagnostic or prognostic marker in MS patients.

The article presents data on assessing the state of the humoral immunity in patients with chronic viral hepatitis B, combined with chronic non-calculous cholecystitis, as chronic liver viral lesions are immune-mediated condition, depending on the replicative activity of the virus and the immune system’s responses to this virus. At the same time, there is an increase in the overall level of CIC in serum and an imbalance in the molecular composition of immune complexes, as well as a decrease in the immunological reactivity in such patients.

The analysis of published and original data demonstrates that prenatal stress induced by viral and bacterial infection, or changes in the physiological concentrations of neurohormones in early ontogeny can cause unfavorable impacts on the development of neuroendocrine and immune systems. In early pregnancy bacterial infection simulated by lipopolysaccharide in an experiment activates the maternal immune system, which enhances the synthesis of pro- and anti-inflammatory cytokines in both maternal and fetal organisms. Consequently, cytokines promote the secretion of a hormonal cascade in the hypothalamic-pituitary-adrenal system, thus eliciting the hormonal response to stress. Various stress factors during critical periods of neuroendocrine and immune system development modulate the epigenetic mechanisms controlling specific genes, which can affect the structure and function of these systems and increase the risk of various pathologies in the offspring.

The purpose of this research is to study the prognostic role of cytokines in plasma in patients with cerebral infarction while assessing the risk of hemorrhagic transformation.Materials and methods. Three groups of patients were identified. Group 1: 66 patients with cerebral infarction without hemorrhagic transformation (CI without HT), mean age 63.9 ± 1.3 years. Group 2: 27 patients with cerebral infarction and with hemorrhagic transformation (CI with HT), mean age was 65.9 ± 2.5 years. Group 3: 65 patients with cerebral hemorrhage (CH), average age - 58.8 ± 1.6 years. The plasma cytokines concentration measurement (IL-1β, TNF-α, IL-6, IL-8, IFN-γ, IL-1Ra, IL-10, IL-4) was performed on the 1st, 2nd and 10th days after the stroke manifestation. The control group - 55 donors cytokines indicators.Results. In the CI with HT group, compared with the CI without HT group and the CH group, the lowest levels of IL-1β and TNF-α were detected on the 1st, 2nd and 10th day since the disease symptoms, and, conversely, the highest IL-1Pa values were revealed on the 1st and 2nd days; IL-4 values - on the 1st and 10th days (p < 0.05). The high HT development risk factors on the 1st day of the disease symptoms are IL-6 ≥ 46.6 pg/ml, IL-8 ≥ 14.7 pg/ml, IL-10 ≥ 12.1 pg/ml, IL-4 ≥ 7.6 pg/ml. In contrast, IL-1β ≥ 1.9 pg/ml, TNF-α ≥ 14.4 pg/ml indicate a low probability of HT development.Conclusion. Predictors of the CI HT development risk on the 1st day of the disease are plasma cytokines indicators IL-1β, TNF-α, IL-6, IL-8, IL-10, IL-4.

In recent years, attention of researches has focused on glial cells of different brain formations - astrocytes and microglial cells. This is due to active role of these cells in ensuring synaptic plasticity and regulation of neurogenesis. The study aimed at analyzing the structural organization of microglia and astrocytes of the human brain substantia nigra, which is the main dopaminergic nerve center. For the study, material from the archive of the Morphology Department (Institute of Experimental Medicine, Saint Petersburg, Russia) was used. Cells were detected using immunocytochemical markers (GFAP for astrocytes and Iba-1 for microglia). It has been established that microglial cells bodies in substantia nigra are located in neuropile singly. In pars compacta of substantia nigra these cells distributed relatively evenly, rarely being in close proximity to neurons. An unexpected fact was that the processes of microglia cells of the human brain substantia nigra have a sufficiently large thickness - 1.5-3 microns, which is not typical for a ramified microglia. Astrocytes of substantis nigra were characterized by the presence of very long processes (more than 100 microns) and the formation of the pericellular sheath around the nerve cells. These sheaths consisted of a dense interweaving of thin sparingly branched astrocyte processes. The processes of microglia were rarely present within such sheaths. The results obtained indicate moderate activation of microglia in substantia nigra and the special role of astrocytes in ensuring the compartmentalization of the pericellular zones in this nerve center.

The purpose of the work is to evaluate the features of the organization of the bioelectrical activity of the brain with different levels of serotonin in the serum of peripheral blood in young people 15-17 years old. The study involved 93 healthy girls and boys (15-17 years) of the Arkhangelsk region and the Nenets autonomous okrug. A serotonin level is determined in serum by enzyme immunoassay using a set of “Serotonin ELISA”. The electroencephalogram (EEG) power spectrum (PS) in the alpha, beta and theta frequencies ranges was recorded using an electroencephalograph “Encephalan” (Medicom, Taganrog). Age-dependent electroencephalogram (EEG) patterns is associated with the level of serotonin in peripheral blood in adolescents. On the background of a higher level of serotonin in the blood, compared to girls, boys have localized associations of theta and beta1 activity of EEG and serotonin levels, mainly in the right frontal-temporal region. In girls, the spectral power level of the EEG theta activity is more dependent on the level of serotonin in the blood, and a greater number of brain areas are involved in correlation interactions in comparison with young men (temporal regions on the left and frontal, central, parietal regions of both hemispheres of the brain).

105 children aged 1-17 years with viral encephalitis (EF) were examined. Determined cytokines (TNF-α, IL-4, IL-10, IFN-α and IFN-γ) in serum and CSF. In acute course (n = 50) dominated (74%) Th1 type of immune response (IR) with a high average IFN-γ in the blood and CSF and IFN-γ / IL-4 = 8.3 and 11.9. With a prolonged flow (n = 25) - Th2 with indices IFN-γ / IL-4 = 0.75 and 0.79. In chronic (n = 30) - suppressive type of IR, in which the blood cytokines did not exceed the norm, and CSF were lower than in acute and prolonged course. Cytokines in acute and prolonged course of EF were higher in serum, and in chronic ~ 1.3-1.7 times higher in CSF than in blood, indicating their intrathecal synthesis in the long-term course of neu-roinfection. Types of IR and the intensity of cytokine synthesis were interrelated with the nature of the course of EF in children and the severity of infectious and cerebral symptoms.

The aim was to study the effect of infrared laser irradiation of average intensity with the total dose of 112 J/cm2 and 450 J/cm2 on the expression of vascular endothelial growth factor (VEGF) in thyroid tissue in normal and hypothyroidism. The experiment was conducted on 30 male laboratory rats. Animals were removed from the experiment one day after irradiation. Expression of vascular endothelial growth factor was determined by immunohistochemical method. It was shown that laser exposure in the studied doses increases the expression of VEGF in the thyroid gland of intact animals and, to a greater extent, in hypothyroid animal groups. When comparing the effects of the two studied modes of laser exposure, it was found that VEGF expression is greater after exposition to the total dose density of 450 J/cm2 on the skin surface. The obtained results could be used for further development of laser therapy methods for hypothyroidism in experiment.

The gene and cell therapy, stimulating the regeneration of damaged nerves is currently under development. In these experiments mesenchymal stem cells (MSCs) are often used. The purpose of this study is to describe the localization and morphological features of mesenchymal stem cells derived from bone marrow after their allografting into the damaged rat nerve. MSCs of the bone marrow of Wistar-Kyoto rats were obtained from Transtechnology LLC (Head G.Polyntsev, Ph.D.). MSCs were cultured, identified and labeled by 5-bromo-2’-deoxyuridine (BrdU) in vitro. The sciatic nerve of adult Wistar-Kyoto rats (n = 12) was damaged (ligature, 40 sec), and the suspension of BrdU+ MSCs (5 · 104 cells in 5 μl per animal) was immediately transplanted into the damaged sciatic nerve. In a previous study, we have showed that some transplanted cells are located in the epineurium of the recipient’s nerve. The perineurium of the recipient rats was studied in the present work. Perineurial cells have polygonal form, thin and flat cell nucleus and form several layers, the basement membranes being placed between them. Perineurium is characterized by the presence of occluding junctions that can be identified using anti-claudine antibodies. The use of antibodies to claudine allowed us to identify perineurium. Some BrdU+ MSCs were found to survive 5-7 d following surgery and according to their localization and morphology became perineurium cells. Such extracellular matrix proteins as laminin, fibronectin, collagen are present in the perineurium. Apparently, the presence of these proteins creates a favorable biological environment for MSCs survival and for their differentiation towards perineurium cells. The results of the study confirm the mesenchymal origin of perineurium cells.

The mechanism of local effects of broadband stochastically organized electromagnetic radiation (BBSO EMR) on formalin-induced edema accompanied by pain was studied at the level of integral adaptational reactions (AR). Leukogram evaluation criteria by Garkavi-Kvakina-Ukolova were used to identify types of AR and their tension (reactivity levels). Significant differences were found between the adaptation body response formed in formalin-induced edema by the type of unproductive reaction of over-activation (OA) and an integral mechanism of the bioadaptive effect of BBSO EMR - the development of stable AR of the calm (CA) and elevated activation (EA) at high reactivity levels.

A clinical case of the asymptomatic onset of HIV-infection on the background of clinically significant osteochondrosis and hypertension in the absence of an epidemiological history, and an analysis of the scientific literature on the problem are presented. It is important to note the low level of viral load in the patient, but there are conflicting reports in the literature about the correlation of levels of HIV viral RNA in the cerebrospinal fluid in patients with neurological manifestations. The treatment and diagnostic tactics in diagnostically unclear cases are discussed.

The in vitro antimicrobial action of human leukocyte lysozyme from on gram-positive bacterium Listeria monocytogenes under various medium conditions was studied. It was shown that in a low ionic strength buffer (without NaCl), lower doses of lysozyme are required to reveal the microbicidal effect than in the case of 0.075 or 0.15 M NaCl. The bacterial growth phase does not significantly affect the antimicrobial activity of lysozyme. The results obtained are consistent with the two-stage mechanism of the antimicrobial action of lysozyme, which includes enzymatic and non-enzymatic action.

The data on properties of thymosin β4, a conserved multifunctional polypeptide of mammals is summarized. Attention has been focused on regulatory activity of thymosin β4 in regard to immune and nervous system components. In these systems thymosin β4 is present in different cell types both stationary and mobile ones. Besides intracellular localization thymosin β4 is also located in extracellular fluids. Inside cells, thymosin β4 has been postulated to regulate actin polymerization as a G-actin-sequestering molecule. But molecular mechanisms of thymosin β4 located extra cells on cell functions remain unclear. The structural-functional organization of thymosin β4 is also discussed. Thymosin β4 is a perspective medicine preparation for the therapy of diseases related to immune and neurological disturbances in patients.

Search for new tools for combating infectious diseases and investigation of molecular mechanisms of their antimicrobial action in in vitro and in vivo models are the urgent tasks of experimental medicine and pathophysiology. A promising direction for the development of new effective antibiotic drugs is creation of analogues of natural protective molecules that provide a host defense against pathogenic bacteria, in particular analogues of antimicrobial peptides of the innate immune system. The aim of our work was design, chemical synthesis and characterization of antimicrobial and hemolytic activity of a peptide protegrin 1 (PG1) structural variants. Three analogues of PG1 were produced and studied, it was shown that two PG1 variants exhibit a high activity against antibiotic-resistant bacteria. A comparative analysis of the hemolytic activity of the peptides towards human erythrocytes was carried out. The ways of further work directed to creation of novel antimicrobials based on a natural peptide PG1 for combating drug-resistant bacteria are outlined.

The aim of the study was to elucidate the molecular mechanisms of modulation of the NaV1.8 channels with a synthetic tetrapeptide (Ac-RERR-NH2). Our data suggest that this substance specifically modulates the activation gating device of these channels, which are responsible for coding of pain signals. This agent (0.1 nM) has a neurite-stimulating effect, which indicates its possible physiological regeneration effect on the nervous tissue. The results obtained allow us to conclude that the agent under study can claim to be the drug substance of a safe and effective analgesic.

98 infants with acute bronchitis aged 3-36 months showed general basic adaptive response on the acute stage: depression of cellular immune response, active humoral immune response, CIC increase and enhanced phagocytic capacity of neutrophils. ACTH and TSH levels were elevated against depletion of cortisol and triiodothyronine levels. Clinical markers together with immune and endocrine predictive markers of the disease severity, character of complications and comorbidity were revealed. Thymogen is indicated for treatment in case of prevailing of hyperergic disorders both in the central core of neurohumoral regulation and the intra-immune - IgA increase. Thymaline proves effective in hyperergia treatment - thymomegaly with low IgA and cortisol levels along with pre-existing bacterial infections.

Saliva is an important biological fluid that reflects human’s health. Its main function is protection of the oral cavity from pathogens. Antimicrobial peptides (AMPs) of the innate immunity may play an important role in anti-infectious defense of the oral cavity, but their relative amount in saliva is low. It’s major component is Proline-rich peptides (PRPs), whose impact in antimicrobial protection remains poorly understood. We suggest that salivary PRPs may reveal their defensive functions upon interaction with other molecules, in particular with AMPs. The aim of this work is an investigation of the combined antibacterial action of salivary PRPs (fragments of Basic salivary proline-rich protein 1: P-H (37-51), IB6 (98-116), p1932) with antimicrobial peptides (histatin 5 and cathelicidin LL-37 and beta-defensin hBD3). Listed PRPs have been obtained by chemical solid-phase synthesis. The method of broth microdilutions was used to compare minimal inhibitory concentrations (MICs) of individual fractions of AMPs and their MICs in the presence of salivary peptides. It was found that in the presence of peptides IB6 (98-116) or P-H (37-51) the activity of defensin hBD3 was increased (reduction of MICs by 2 times) against Staphylococcus aureus SG511. In the presence of IB6 (98-116) or p1932 the activity of this defensin against E. coli ML35p was also improved (MICs of hBD3 was lowered by 2 times). For other combinations of the peptides, this effect was not observed. The obtained data confirm the assumption that the combined action of varied salivary peptides, including cationic Proline-rich peptides, plays an important role in anti-infectious protection of the oral cavity.

Sensitive receptors of the olfactory sensory system are located in the nasal cavity mucosa. The aim of this study was to evaluate the human beta-defensin-3 (hBD-3) gene expression in the surface epithelium of the nasal and sinonasal mucosa. Surgical samples from patients with nasal and sinonasal disease (n = 85) (sinus maxillaries mucosa, choana polyps, middle nasal passage polyps, sinus maxillaries polyps, inferior turbinate mucosa of hypertrophic rhinitis, inferior turbinate mucosa and the middle nasal passage mucosa as controls) were investigated. Total RNA was extracted and analysed by real-time RT-PCR for hBD-3 as well as beta-actin mRNA.hBD-3 gene expression was detected in all examined anatomical regions in 14.29-33.33% samples at low levels, but it was absent in the hypertrophic inferior turbinate mucosa (Fisher’s exact test, p < 0.05 compared to the middle nasal passage mucosa; p < 0.01, odds ratio (OR) 31.15, 95% confidence interval (CI) 1.53÷633.6 compared to the middle nasal passage polyps). The highest hBD-3 mRNA expression detection frequency was detected in the middle nasal passage polyps (53.84% cases) (p < 0.05, OR 7.00, CI 1.10÷44.63 compared to the sinus maxillaries mucosa). The highest levels of hBD-3 gene expression was detected in the middle nasal passage polyps also (Wilcoxon signed rank test, p < 0.05 compared to the hypertrophic inferior turbinate mucosa). Clinically, inflammatory polyps are found in the middle turbinate in patients with chronic rhinosinusitis but not in the inferior turbinate. In the context of chronic inflammation, apart from direct antimicrobial activity, high concentrations hBD-3 also potentially contributes to epithelial injury and fibrotic remodeling.

This study is devoted to an experimental study of the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the intensity of lipid peroxidation of the thymus and spleen lipids of male rats under conditions of “social” stress. “Social” stress in animals was modeled by the formation of aggressive and submissive behavior of males in the conditions of distant sensory contact. The intensity of lipid peroxidation (LPO) in the thymus and spleen was determined by spectrophotometry using three indicators: the initial level of products reacting with thiobarbituric acid (TBA-reactive products), the rate of spontaneous and induced by ascorbate and iron ions of LPO. “Social” stress is accompanied by an increase in peroxidation processes in immunocompetent organs, which contributes to the development of stress-induced functional disorders of the immune system. Against the background of Semax administration under “social” stress, its pronounced corrective effect on lipid peroxidation rates is observed, as evidenced by a decrease in spleen and thymus tissue homogenates of male rats in the initial level of TBA-reactive products, as well as spontaneous and ascorbate-dependent levels of lipid peroxidation.

Antimicrobial peptides (AMPs) have certain resemblance with surfactants. Using checkerboard titrations and spectrophotometrical analysis of the membrane permeability for chromogenic markers, we found that nonionic surfactants “Tritons” significantly increase the speed of membranolytic action of AMPs, and enhance their antibacterial activity.

Traumatic brain injury (TBI) leads to steady stress reaction that may substantially influence on posttraumatic period. Stress changes concentration of sex hormones too, that play role of neurosteroids in CNS. The aim of the study was to detect changes in corticosterone and testosterone concentration in serum of experimental animals during recovery period after TBI. And also to find possibility of disturbance correction by cytokine preparation rIL-2 (ronkoleukin). After TBI both experimental and control group of animals get daily injections of recombinant human interleukin-2. TBI decreased the level of corticosterone on 30%, the injection of rIL-2 increased it. Testosterone slightly changed after TBI. But it’s level increased when after TBI the injections of rIL-2 were done. The obtained results can be considered as evidence of the stress reaction normalization in animals after TBI and under the conditions of their treatment with rIL-2.

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several semaphorins, so-called ‘immune semaphorins’, are also involved in various phases of immune responses. One of such factors is semaphorin 3A - a member of class 3 semaphorins, which are secretory molecules in vertebrates. There are multiple mechanisms involved in the process of semaphorin 3A-mediated regulation. One of them is down-regulation of peripheral T-cell activity in consequence of which semaphorin 3A is considered as an immunosuppressive factor. But semaphorin 3A is also expressed in the thymus while its function there remains obscure. Here are discussed new data on immunosuppressive function of this factor towards thymocytes and thymic epithelial cells, obtained in vitro. Because it is involved both in physiological immunoregulation and in the pathogenesis of many autoimmune, atopic, and malignant diseases, semaphorin 3A turns to be a promising therapeutic tool to be studied and applied in these diseases.

Antiapoptosis activity of plant polyprenylphosphate against macrophage target cells infected with the murine encephalomyelitis virus. Infection caused by the Theiler’s murine encephalomyelitis virus (TMEV) is regarded as an experimental model of multiple sclerosis, since both of these diseases are characterized by similar pathology of the central nervous system tissues and involvement of the immune system in the development of the demielinization. The aim of the work was to study the effect of plant-derived polyprenylphosphate (PP) on the apoptosis of infected target cells. We showed that PP reduced apoptosis of macrophage target cells infected with TMEV. It is known that in the protocol of multiple sclerosis treatment some medicines possessing immunomodulatory, antiviral, anti-inflammatory and antioxidant activity are used. Since PPs of plant origin also have all these activities, the prospects of their use as therapeutic agents are discussed.

Azoles are the main antifungal drug class. The main mechanism of the azoles action is the intercalation in the sterol biosynthesis regulation. At the same time, the effect of the azole derivates on mammals is antiatherogenic. But there were no publication about connection between azole derivates effect on hyperlipidemia and expression of genes with antiatherogenic effects. In our work we used triton model of hyperlipodemia on rats to analyze the effect of carmizole injection on the expression of the main antiatherogenic genes and their regulators Apo A-I, HDL, LDL. We had four groups of rats: intact control group, triton control group, phenophibrate group and carmizole group. During a seven days we gave a per oral injections of carmizole for the carmizole group, phenophibrate (as a comparison drug) for phenophibrate group and 1% starch solution for triton control group. Liver tissue samples were used for RNA extraction and following RT-PCR (Real Time PCR) with primers for Apo A-I mRNA sequence. We have found, that Apo A-I mRNA level decreased in the triton control group to 17%, but restored up to 89% in the carmizole group. Carmizole derivate drug works like stimulator of Apo A-I gene expression. That increasing of the expression of antiatherogenic protein gene could me the base of the antiatherogenic effect of the carmizole derivate.

The purpose of this work was to study the effect of turmeric extract on behavior indicators, the severity of the cellular immune response in animals in a state of experimental alcoholism. Experimental models: mouse males (CBAxC57Bl/6)F1 three months of age (n = 60). Alcohol dependence in experimental animals was formed by the method of 6-month soldering with a 10% ethanol solution. In the control groups, the animals received per os water or 10% ethanol solution, in the experimental group - an extract of turmeric powder in a solution of ethanol. Mice behavior was assessed in the “open field” test. The severity of the cellular immune response to sheep erythrocytes was assessed by the intensity of the development of a delayed-type hypersensitivity reaction.It was found that the use of turmeric extract against the background of taking ethanol solution in animals with experimental alcoholism leads to the stimulation of behavior and the increase of the cellular immune response to the level characteristic of healthy animals of the corresponding age.Results indicates the protective effect of turmeric on a number of parameters of the functional activity of the nervous and immune systems during chronic ethanol intoxication.

Comprehensive treatment of patients with multiple sclerosis (MS) is still relevant. The complex pathogenesis and acute incidence of MS in young people requires the use of multifunctional drugs with a protective effect, including antioxidants. The purpose of this study is to identify a corrective neuroprotective and immune modulating effect of the synthetic drug Triafen-2 (Trf-2), obtained in optimized way. Trf-2 was used at a dose of 50 mg/kg orally with chronic administration in II parts of experiments. To create an adequate model of MS - autoimmune encephalomyelitis (EAE), immunization of guinea pigs with an encephalitic mixture was used in Freund’s complete adjuvant. Mortality, a number of immunological parameters, the clinical picture of neurological complications and the severity of CNS damage in guinea pigs were determined. We studied morphologically the development of T-lymphocytic infiltration of the brain and spinal cord, demyelination of nerve fibers, the degree of cerebellar disorders, disorders of the pelvic organs, the presence of paresis and paralysis. A significant decrease in mortality was shown and protective effect of Trf-2 on neurological symptoms of EAE was noted. The reduction and even complete absence of paresis and paralysis in 66.5% of guinea pigs in the experimental group compared with animals that did not receive treatment was determined. A positive effect of Trf-2 on the migration activity of leukocytes and antibodies in the blood was found. In the group with Trf-2, there was a decrease in the content of lipid hydroperoxides and malonic dialdehyde. A pronounced neuroprotective and immune modulating effect of Triafen-2, which inhibits pathological disorders in an experimental model of EAE, has been established. The results justify the need for further study of Triafen-2 as a promising corrective drug.

With the help of BAS (biologically active substances), you can increase the ability of the cells of the body to maintain the constancy of its internal environment. The general condition improves, the prophylactic effect increases and mortality decreases, the weight gain in young animals grows. The cost of production is reduced.

Experimental prostatitis in rats was reproduced by administering a 0.05% formaldehyde solution of 0.01 ml on the background of benign prostatic hyperplasia, which was simulated by chronic administration of sulpiride 40 mg/kg for 30 days. From the 26th to the 30th day of the course administration of sulpiride, one of the immunomodulators was injected into the animals: polyoxidonium 0.75 mg/kg, trekrezan 25 mg/kg or metaprot 25 mg/kg. Control rats received saline in an equivalent volume (0.2 ml). The volume of the prostate gland of rats under the influence of sulpiride increased 2.5 times, and after the introduction of formaldehyde into the gland - even more than 3 times. Experimental prostatitis was accompanied by a decrease (by 30-39%) in the concentrations of anti-inflammatory cytokines (IL-4 and IL-10), the immunoregulator IL-2, and IL-12 (p70), the level of interferon-γ has not changed. The pool of pro-inflammatory cytokines increased (IL-1β and IL-17 - by 33% and 75%, respectively, TNFα, IL-6, and MCP-1 chemokine - by more than 2-3 times). Against this background, the concentration of the anti-inflammatory cytokine IL-13 increased by more than 4 times. A course of administration (5 days) of immunomodulators, polyoxidonium, trekrezan or metaprot reduced the volume of the prostate gland by 28-44% and optimized blood levels of IL-1β, IL-17A, IL-13 and chemokine. The level of pro-inflammatory (IL-2, IL-12, INFα) and anti-inflammatory cytokines (IL-4 and IL-10) has become much higher. The limitation of the cytotoxic effect of IL-6, one of the leading inflammatory mediators, is noted. The effectiveness of immunomodulators was as follows: polyoxidonium > trekrezan > metaprot (in descending order of activity). Apparently, the restoration of the immunoregulatory function of anti-inflammatory cytokines IL-4 and IL-10 and the restriction of the production of pro-inflammatory cytokines is one of the sanogenetic mechanisms of the complex adaptive action of the studied drugs.

The severity of pain and changes in the adaptational status were studied in patients with brain metastases or cervical cancer receiving xenon therapy after whole brain radiotherapy or after radical hysterectomy. Hematological indicators of the nature and tensiton of general nonspecific adaptional reactions of the body (ARs) by Garkavi-Kvakina-Ukolova, the QLQ-C15 questionnaire and a 10-point graphic visual analogue scale for the assessment of the intensity of pain were used. Xenon caused concurrent reduce in the intensity of pain and improvement of characteristics of ARs in all studied patients. The results suggested an association between the analgesic effect of xenon and the normalization of neuroimmune processes and reduced damaging effects of special antitumor treatment on the body under the influence of xenon.

The purpose of this study is to determine the effect of orexin A to LPS-activated microglia by investigating the morphological change. The effect of orexin on the level of LPS-activated microglia activation during the transition to the M1 phenotype was determined, which can be studied by measuring the cell area of the body.

The study of the mechanisms of functioning of the immune system under stress does not lose its relevance for decades. An important factor in the neuroendocrine regulation of immunity during stress is the endogenous opioid system. In the present work, we evaluated the effect of various cold stress variants on the production of cytokines IL-1β and IL-10 by the cells of the mouse peritoneal cavity under conditions of blockade of opiate receptors. It was established that acute and chronic cold stress, regardless of duration, did not affect the production of IL-1β and increased the production of IL-10 by peritoneal macrophages, this effect was canceled by the introduction of naloxone. The effect of chronic cold stress on IL-10 production depended on cell activation. In all variants of stress, an increase in plasma corticosterone concentration was observed, which did not depend on the blockade of opiate receptors. The work was performed in the framework of the state task, the number of the state registration of the topic No. 01201353248.