Vol 19, No 1S (2019)

Articles
In Memoriam and Tribute to George Freeman Solomon Professor Emeritus of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles1931-2001
Orlov D.S.
Abstract
“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.
Medical academic journal. 2019;19(1S):5-7
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SOLUBLE FORMS OF IMMUNE CHECK-POINT RECEPTOR PD-1 AND ITS LIGAND PD-L1 IN PERIPHERAL BLOOD OF ONCOLOGIC PATIENTS: CLINICAL AND PATHOLOGIC CORRELATIONS
Alferov A.A., Gershtein E.S., Naberezhnov D.S., Goryatcheva I.O., Kushlinskii N.E.
Abstract
The levels proteins of control points of immunity sPD-1, sPD-L1 in serum or plasma of 366 patients with malignant tumors of various nosological forms treated at the N.N. Blokhin National Medical Research Center of Oncology. A correlation of sPD-L1 with the prevalence of the process and the degree of tumor malignancy, as well as a positive correlation with some other tumor markers of blood, was found: VEGF, VEGFR1, MMP-7, MMP-8, TIMP-1.
Medical academic journal. 2019;19(1S):8-9
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CYTOKINE CONTENT WITHIN BRAIN STRUCTURES IN RATS WITH GENETIC PREDISPOSITION TO DIFFERENT LEVELS OF AGGRESSION
Alperina E.L., Zhukova E.N.
Abstract
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.
Medical academic journal. 2019;19(1S):9-10
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MARKERS OF INFLAMMATION IN THE BLOOD PLASMA OF PATIENTS WITH FRONTOTEMPORAL DEMENTIA
Androsova L.V., Zozulya S.A., Mikhailova N.M., Fedorova Y.B., Klyushnik T.P.
Abstract
The aim of this work was to identify several markers of inflammation in the blood of patients with frontotemporal dementia (FTD). 34 patients were surveyed with FTD. The control group consisted of 35 age- and sex- matched healthy people. Blood plasma was used for immunological studies. The enzymatic activity of leukocyte elastase (LE) and the functional activity of the α1-proteinase inhibitor (α1-PI) were determined by a spectrophotometric method, the concentration of interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by ELISE. A statistically significant increase in α1-PI activity (p < 0.0001) was detected in patients with FTD; no difference from control was found for other indicators. There is a significant variation in all indicators, i.e. both increase and decrease of values compared to the control group. According to the level of LE activity, two immunophenotypes were identified. 73.5% of patients with FTD have an immunophenotype characteristic of patients with endogenous psychosis and 26.5% of patients have an immunophenotype similar to Alzheimer’s disease. The data obtained indicate the involvement of inflammatory reactions in the development of FTD and the heterogeneity of this disease as assed by immunological parameters.
Medical academic journal. 2019;19(1S):10-12
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STATE OF CYTOKINES, ALPHA-AMYLASE AS A MARKERS OF AUTONOMOUS NERVOUS SYSTEM AND CORRECTION WATER DRINKING BEHAVIOR
Baisheva G.M., Melnik K.N.
Abstract
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.
Medical academic journal. 2019;19(1S):12-14
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GLUCOSE CAN EPIGENETICALLY ALTER THE GENE EXPRESSION OF NEUROTROPHIC FACTORS IN THE MURINE BRAIN CELLS
Oomura Y., Hossain M.S.
Abstract
Glucose is believed to improve the memory in both human and mice, but the detailed insights were mostly elusive. In this study, we focused on two major neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 1 (FGF1), which are believed to be associated with the memory enhancement and assessed their expressional regulation among the murine neuronal and glial cells. Our findings showed that the glucose administration increased phosphorylated Akt, phosphorylated CREB, exon 1- and exon 4-specific BDNF transcripts, and FGF1 transcripts that are associated with the epigenetic changes expected to open the chromatin and a reduction in histone deacetylase 2 (HDAC2) in neurons and astrocytes of the murine hippocampus. The glucose administration enhanced the long-term potentiation and the number of dendritic spines in the CA1 and CA3 subfields of hippocampus. The intrahippocampal injection of short hairpin RNA against TrkB canceled the glucose-mediated memory enhancement. Like the glucose, we also report that the HDAC inhibitor can enhance the memory through the BDNF-TrkB pathway but it targeted different brain cell populations to enhance the BDNF and FGF1 transcripts. In addition, the soluble FGF1 treatments significantly increased the BDNF expression in astrocytes and neurons, suggesting that the glucose-mediated induction of the neurotrophic factors could contribute to the memory. Our study provides the valuable insights, explaining the distinctive neuronal and glial cell regulation of the neurotrophic factors by glucose and HDAC inhibitor, which could likely explain how our brain cells can control the release of neurotrophic factors.
Medical academic journal. 2019;19(1S):14-15
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PLASMALOGENS ENHANCE SPATIAL MEMORY BY INCREASING SYNAPTIC PLASTICITY
Hossain M.S., Fujino T.
Abstract
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.
Medical academic journal. 2019;19(1S):15-15
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THE EFFECT OF PRO-INFLAMMATORY CYTOKINE IL-1β ON THE CENTRAL AND PERIPHERAL RESPIRATORY CONTROL MECHANISMS ON THE BACKGROUND OF SEVERE HYPOXIA
Baranova E.V.
Abstract
Pro-inflammatory cytokine IL-1β, as inflammatory mediators participate in neuroimmune interactions in the central nervous system. It’s assumed that IL-1β affect the central and peripheral breathing control in acute hypoxia that occurs simultaneously with systemic inflammation. The purpose of this study was to evaluate the influence IL-1β on respiratory responses following progressive hypoxia and ability to survive after hypoxic apnea. We studied the influence of IL-1β (10 μg/kg) on respiration and the ability to survive acute hypoxic challenge in anesthetized Wistar rats. The response of tidal volume, breathing rate, minute lung ventilation, oxygen saturation, during acute hypoxia was examined using pneumotachography methods. Increasing hypoxia was created by rebreathing method. The results indicated that during progressive acute hypoxia animals given IL-1β were unable to sustain breathing efforts for as long as control rats. Following hypoxic apnea IL-1β decrease the ability to autoresuscitate compared with control groups. Thus IL-1β reduces the tolerance of animals to acute hypoxia and the ability to spontaneously autoresuscitate after apnea. We assume that that IL-1β inhibit inspiratory neurons and decrease the sensitivity of the carotid chemoreceptors to hypoxic stimulation.
Medical academic journal. 2019;19(1S):15-16
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CYCLOOXYGENASE MECHANISMS IN THE REGULATION OF RESPIRATORY EFFECTS OF TUMOR NECROSIS FACTOR
Danilova G.A., Klinnikova A.A., Aleksandrova N.P.
Abstract
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.
Medical academic journal. 2019;19(1S):17-17
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CYTOKINES AND BRAIN-DERIVED NEUROTROPHIC FACTOR IN CONTEXT OF COGNITIVE IMPAIRMENT IN THE ELDERLY
Filippova Y.Y., Kholodilina M.E., Burmistrova A.L.
Abstract
The aim is to assess the levels of certain cytokines IL-6, TNF-α, IL-1β и IL-10, and BDNF in the blood plasma of the elderly, depending on degree of cognitive impairment. 65 elderly with (vascular dementia) or without cognitive impairment were enrolled in the study. The level of cytokines and BDNF were measured in plasma by ELISA. It was found that, regardless of the degree of cognitive impairment, the condition of systemic chronic low-grade inflammation is characteristic of the elderly. Against this background, plasma levels of BDNF were increased in elderly with vascular dementia, reaching statistical significance compared with healthy individuals. Such changes in the level of BDNF may reflect a compensatory repair mechanism in neurodegeneration or be associated with a defective axonal transport or utilization of BDNF in the central nervous system paralleled by increased serum concentrations.
Medical academic journal. 2019;19(1S):18-19
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CHARACTERISTICS OF CYTOKINE REGULATION AND CARTILAGINOUS TISSUE METABOLISM AT PRIMARY AND POST-TRAUMATIC OSTEOARTHRITIS
Gladkova E.V., Ivanov A.N.
Abstract
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.
Medical academic journal. 2019;19(1S):19-21
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BIOCHEMICAL ALTERATIONS IN ONCOPEDIATRIC PATIENTS DURING SEPSIS
Golovnya E.G., Lebedeva A.V., Kharitidi T.Y., Sotnikov A.V.
Abstract
In the current study, biochemical abnormalities occurring in the body of children with cancer in sepsis, as well as their relationship with the new marker of sepsis and phagocytosis by presepsin, are considered. A survey enrolled 112 children who were treated at the N.N. Blokhin National Medical Research Center of Oncology. Differences in medians of a number of biochemical parameters in groups of patients who survived and died of sepsis were revealed.
Medical academic journal. 2019;19(1S):21-22
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NEUROENDOCRINE AND MAST CELLS OF THE SKIN IN THE AREA OF ACUPUNCTURE
Guryanova E.A., Deomidov E.S.
Abstract
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.
Medical academic journal. 2019;19(1S):22-24
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LIPOPOLYSACCHARIDE-INDUCED IMMUNOLOGICAL STRESS AT EARLY STAGES OF PREGNANCY AFFECTS THE DEVELOPMENT OF GONADOTROPIN RELEASING-HORMONE (GNRH)-PRODUCING SYSTEM
Ignatiuk V.M., Izvolskaia M.S.
Abstract
The aim of the present work was to study the development of afferent bonds between GnRH- and monoaminergic neurons in rat fetuses and to identify possible targets affected by LPS-induced inflammation. The innervation was analyzed using retrograde tracing method with DiI dye. At ED17 and ED21 olfactory bulbs (the area of GnRH migration) are innervated with monoaminergic neurons of septum and in lateral hypothalamus. The GnRH- and monoaminergic neuron interaction zones are sensitive to LPS (E. coli) prenatal exposure, which induces pro-inflammatory cytokine synthesis. We suppose that the olfactory bulbs of fetal forebrain can be a possible area of cytokine influence on GnRH- and monoaminergic neuron interaction.
Medical academic journal. 2019;19(1S):24-26
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PARTICIPATION OF INOS IN THE EFFECT OF IL-1β ON LUNG VENTILATION AND HYPOXIC CHEMORECEPTION
Klinnikova A.A., Danilova G.A., Alexandrova N.P.
Abstract
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.
Medical academic journal. 2019;19(1S):26-27
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CELLULAR MECHANISMS OF NEUROPSYCHIATRIC SYMPTOMS INDUCED BY HYPOTHYROIDISM IN MOUSE MODEL
Mami N.
Abstract
Thyroid hormones (THs) are essential not only for the development of the central nervous system (CNS) but also for matured brain function. In the CNS, circulating thyroxine (T4) crosses blood-brain barrier via specific transporters and is taken up to astrocytes, becomes L-tri-iodothyronine (3, 3’, 5-triiodothyronine; T3), an active form of TH, by type 2 de-iodinase (D2). T3 is released to the brain parenchyma from astrocytes (glioendocrine system). In adult CNS, both hypo- and hyper-thyroidism, the prevalence in female being > 10 times higher than that in male, may affect psychological condition and potentially increase the risk of cognitive impairment and neurodegeneration including Alzheimer’s disease (AD). We have reported, that non-genomic effects of T3 on microglial functions and its signaling [1] and sex- and age-dependent effects of THs on glial morphology in the mouse brains of hyperthyroidism [2, 3]. Behavioral changes and spine density in hippocampus also showed sex-dependence. Recently we analyzed the opposite thyroid dysfunction, hypothyroidism, and found sex- and age-dependent changes in glial morphology and animal behavior as well. These results may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hyper- and hypothyroidism affect psychological condition and cognition.
Medical academic journal. 2019;19(1S):27-28
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CLINICAL VALUE OF BIOCHEMICAL MARKERS OF NEUROENDOCRINE TUMORS
Lyubimova N.V., Timofeev Y.S., Toms M.G., Kharitidi T.Y., Vashketova O.I., Kushlinski N.E.
Abstract
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.
Medical academic journal. 2019;19(1S):28-29
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THE EFFECT OF GLUTAMATE ON THE MIGRATION OF T CELLS FROM HEALTHY DONORS AND PATIENTS WITH MULTIPLE SCLEROSIS IN VITRO
Maksimova M.A., Kuzmina U.S., Bakhtiyarova K.Z., Vakhitova Y.V.
Abstract
Aim of study. To study chemotactic properties of glutamate and glutamate receptor agonists on T cells migration from healthy donors and patients with multiple sclerosis (MS) in vitro. Materials and methods. T cell migration of 15 patients with MS and 15 healthy donors was studied in vitro using transwells. Lymphocytes were activated with PMA (10 ng/mL). T cells were added to transwells with fibronectin (10 μg/mL) pretreated membrane. The lower chamber contained glutamate or AMPA or NMDA (100 μM for each) in complete RPMI medium. Migrated cells were collected and stained with antibodies to CD3-marker for subsequent analysis by cytofluorimetry. Results and conclusion. In presence of glutamate, there is a tendency to a decrease in migration activity in both groups of donors. T-cell chemotaxis of healthy donors, but not MS patients, decreased in concentration gradient of NMDA. The activation of lymphocytes with PMA leads to a decrease in the number of migrated cells by an average of 17% (p < 0.01). In MS patients there is a tendency to an increase in chemotaxis of activated cells in concentration gradient of glutamate, and a decrease with AMPA. Thus, glutamate and glutamate receptors agonists do not possess pronounced chemotactic properties, but rather enhance T-cell migration through synthesis of adhesion molecules on the surface of lymphocytes and endothelium.
Medical academic journal. 2019;19(1S):29-30
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THE ROLE OF THE AUTONOMIC NERVOUS SYSTEM IN THE FORMATION OF NEUROENDOCRINE AND IMMUNE DISORDERS DURING STRESS AND DISSTRESSE
Pesin Y.M., Gabitov V.K., Beisembaev A.A., Potekhina Y.I.
Abstract
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.
Medical academic journal. 2019;19(1S):31-34
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NERVE GROWTH FACTOR AND S100B IN BLOOD AND CEREBROSPINAL FLUID AS INDICATORS OF THE SEVERITY OF ISCHEMIC STROKE
Pivovarova L.P., Voznyuk I.A., Osipova I.V., Gogoleva E.A.
Abstract
Aim. To determine the relationship between the content of nerve growth factor (NGF) and S100b with the clinical manifestations of acute ischemic stroke (IS). Material and methods. A total of 17 patients with IS, age 68.5 (67; 78.5) years were examined; comparison group: 15 volunteers, age 65.0 (62.0; 66.5) years. The patients’ condition was assessed by the size of the brain lesion, the NIHSS and mRS, somatic status. Serum and cerebrospinal fluid (CSF) NGF, S100b, IL6, plasma D-dimer (ELISA) were determined at 1, 3, 10 days after IS. Results. We found NGF decreased in a serum of patients IS with a fatal outcome in 1-10 days. The dependency of serum (r = -0.300, p < 0.05) and CSF (r = -0.271, p < 0.05) NGF with the size of the lesion and patients somatic status (r = -0.322, p < 0.05) was discovered. The concentration of S100b increased from 3 days in deceased patients in the CSF and blood. The S100b correlated with the outcome of the disease (r = 0.650, p < 0.01), NIHSS (r = 0.651, p < 0.01), mRS (r = 0.451, p < 0.05). NGF and S100b levels were associated with the increasing of plasma D-dimer and CSF IL-6. Thus the NGF and S100b reflect the brain damage severity and the patients’ condition in the acute IS and associates with inflammation activity.
Medical academic journal. 2019;19(1S):34-35
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AUTONOMIC NERVOUS REGULATION OF HEART RATE AND BIOELECTRIC BRAIN ACTIVITY AT THE HEART RATE VARIABILITY BIOFEEDBACK IN HUMANS DEPENDING FROM THE INITIAL SERUM TNF-α LEVEL
Poskotinova L.V., Demin D.B., Krivonogova E.V., Stavinskaya O.A., Balashova S.N.
Abstract
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.
Medical academic journal. 2019;19(1S):36-37
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THE EFFECT OF ACUTE HYPEGLYCEMIA ON THE ACTIVITY OF THE ANTIOXIDANT SYSTEM IN THE CENTRAL NERVOUS SYSTEM AND IN THE LIVER OF THE INVERTEBRATE MOLLUSK - LYMNAEA STAGNALIS
Shadenko V.N., Sidorov A.V.
Abstract
Comparison of dynamic changes of biochemical reactions in the liver and CNS of freshwater liver mollusc LYMNAEA STAGNALIS has been conducted. It has been conducted during incubation in the highly concentrated solution of glucose. The indicators of superoxiddismutase (SOD) activity, the level of renewed glutation (G-SH), Se-dependant glutation peroxidase (Se-GP) and TBA-active products were estimated and compared. Also for the tissues of the Central Neural System and tissues samples of liver it was found out by glucoseoxidate method the concentration of glucose in haemolymph of the investigated biological object in the conditions of hyperglycemia. A comparative estimation of the general protein concentration in both tissues was conducted. Resistance of the liver tissue to hyperglycemia and a reverse effect towards CNS was found out.
Medical academic journal. 2019;19(1S):37-39
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PROTEASOME MECHANISMS OF THE DEVELOPMENT OF TOLERANCE TO ALLOGRAFT IN WISTAR AND AUGUST RATS WITH DIFFERENT CONTENT OF MONOAMINES IN THE BRAIN
Astakhova T.M., Karpova Y.D., Bozhok G.A., Alabedal’karim N.M., Lyupina Y.V., Legach E.I., Sharova N.P.
Abstract
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.
Medical academic journal. 2019;19(1S):39-41
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POLYMORPHISM OF INTERLEUKIN 10 IN PATIENTS WITH AN IRRITABLE BOWEL SYNDROME DEPENDING ON PSYCHOPATHOLOGICAL DISORDERS
Stashkevich D.S., Burmistrova A.L.
Abstract
Irritable bowel syndrome, which is a common functional intestinal disorder, can be attributed to psychosomatic pathology, since it contains all three characteristic features of this group of diseases. The study assessed discrimination in the distribution of alleles and genotypes -1082G/A, 819C/T, -592C/A IL-10 in groups of patients with IBS with various psychopathological disorders. The peculiarities of the distribution of alleles and genotypes formed by the polymorphic site -592C/A IL-10 were identified. For groups of patients with “IBS with anxiety disorders” and “IBS with depressive syndrome”, the frequencies of the rare allele and its heterozygous genotype -592C/A were increased. According to the criterion of the odds ratio, prognostic significance was an increase in the carrier frequency only in the group of patients “IBS with anxiety disorders” (OR = 3.9, 95% CI 1.3-12.5). It has been established that the polymorphism -592C/A of the IL-10 gene was associated with the variant “IBS with anxiety disorders”.
Medical academic journal. 2019;19(1S):41-43
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NEUROEPITHELIAL BODIES OF THE RAT’S LUNGS IN EXPERIMENTAL ASTHMA
Syrczova M.A., Korzhevskii D.E.
Abstract
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.
Medical academic journal. 2019;19(1S):43-44
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THE GABA-ERGIC SYSTEM DOES NOT CONTROL THE NOCICEPTIVE RESPONSES OF PRIMARY SENSORY NEURON
Penniyaynen V.A., Podzorova S.A., Terekhin S.G., Krylov B.V., Plakhova V.B.
Abstract
The aim of the study was to elucidate the molecular mechanisms of the interconnection of the GABA-ergic and nociceptive systems at the level of the peripheral division of the CNS. The data obtained indicate that GABA does not affect the activation gating device of the NaV1.8 channel of the primary sensory neuron responsible for coding pain signals.This agent in a wide range of concentrations also does not affect the growth of neurites of sensory neurons of embryonic nervous tissue. These results confirm our assumption, expressed earlier that the asynaptic membrane of the primary nociceptive neuron is not under the control of the GABA-ergic system.
Medical academic journal. 2019;19(1S):44-45
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MAST CELLS AFTER BONE MARROW AUTOTRANSPLANTATION
Vorobyova O.V., Lyubovtseva L.A., Guryanova E.A., Gimaldinova N.E.
Abstract
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.
Medical academic journal. 2019;19(1S):45-47
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CHARACTERISTICS OF ADAPTATIONAL REACTIONS AND MALIGNANT SPREAD IN TUMORS OF VARIOUS LOCATIONS
Zhukova G.V., Shikhlyarova A.I., Gaziev U.M., Zinkovich M.S., Snezhko A.V., Lazutin Y.N., Shevchenko A.N., Bragina M.I., Zhadobina A.I.
Abstract
The character, intensity and quantitative indicator (QI) of general nonspecific adaptational reactions (AR) of the body were studied in patients with lung cancer (LC) or biliopancreatoduodenal cancer (BPDC) with various malignant spread. Poor AR characteristics were associated with the presence of metastases, but did not depend on the surgery volume. AR QI significantly differed depending on the metastatic status in patients with resectable LC receiving similar surgery treatment. AR QI in BPDC patients a day after radical pancreatoduodenal resection was higher than after bypass anastomosis. Thus, the studied AR characteristics demonstrated the state of systemic neuroimmune mechanisms of the nonspecific antitumor resistance of the body.
Medical academic journal. 2019;19(1S):47-48
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HYPOXIC THERAPY IN THE CORRECTION OF NEUROIMMUNOENDOCRINE DISORDERS IN AUTOIMMUNE THYROIDITIS
Abazova Z.K., Borukaeva I.K.
Abstract
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.
Medical academic journal. 2019;19(1S):49-51
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CHANGES OF INTESTINAL MICROBIOME IN MULTIPLE SCLEROSIS ARE ASSOCIATED WITH IMMUNE SHIFT AND PSYCHOEMOTIONAL DISORDERS
Abdurasulova I.N., Matsulevich A.V., Tarasova E.A., Kudryavtsev I.V., Nikiforova I.G., Serebryakova M.K., Miroshnichenko M.I., Ivashkova E.V., Tatarinov A.E., Ilves A.G., Ermolenko E.I., Bisaga G.N., Stolyarov I.D., Klimenko V.M.
Abstract
Recently, the role of the intestinal microbiota in MS has been actively investigated in connection with its influence the development and activity of immune and nervous systems. It is assumed that immune dysfunction, as well as disorders of the gastrointestinal tract and psycho-emotional functions in patients with MS, may be associated with intestinal microbiocenosis dysbiosis. The aim of the study was to assess changes in the intestinal microbiome in MS patients and to analyze the associations of the bacterial level with various subsets of Th cells in the blood and psycho-emotional disorders. 126 MS patients with disease duration of 12.2 ± 0.9 years and 69 healthy individuals were examined. Intestinal microbiome was determined by the Illumina/Solexa sequencing method. The quantitative content of microbial species was determined by the method of cultivation and real time PCR with specific primers, subsets of Th cells - by flow cytometry. Patients were assessed for anxiety, depression, and asthenia. It was shown that the intestinal microbiome of MS patients was significantly changed compared with healthy individuals: the proportion of Bacteroides, especially of the Prevotellaceae family, was reduced, the proportion of Firmicutes (Bacilli and Clostridia) and Actinobacteria was increased, and the symbiotic species in Enterobacteriaceae family were replaced by opportunistic species. A positive correlation between the level of Bifibobacteria spp. with disease severity and blood levels of DP Th17 CM cells. Enterobacter spp. level correlated with the level of “classical” or Th17/22 CM and DP Th17 EM. Bifidobacteria spp. the level was also associated with the level of depression in patients, the level of Escherichia coli and Prevotella spp. - with anxiety, and the level of atypical E. coli and Sutterella spp. - with asthenia. The data obtained suggest that immune and psycho-emotional disorders in patients with MS can be corrected by normalizing intestinal microbiocenosis.
Medical academic journal. 2019;19(1S):51-54
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CLINICAL AND IMMUNOLOGICAL ASPECTS OF CHRONIC HEADACHES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Aleksandrova N.V., Aleksandrov A.V., Alekhina I.Y., Paramonova O.V.
Abstract
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.
Medical academic journal. 2019;19(1S):54-56
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THE ROLE OF SYMPATHIC AND PARASIMPATIC INNERVATION IN NEUROIMMULAR INTERACTIONS WITH EXTERNAL GUINETAL ENDOMETRIOSIS
Andreev A.E., Drobintseva A.O., Polyakova V.O.
Abstract
Currently the study of the role of peripheral nervous system in control of inflammation in endometriosis and its involvement in the development of the chronic pain syndrome in this pathology is of relevance. The purpose of this work was to assess the reciprocal location of sympathetic and parasympathetic nerve fibers with external genital endometriosis at various stages of progression. The samples for the study were the endometrial biopsies of patients of reproductive age with external genital endometriosis of I-IV stage of the disease, with primary sterility (n = 20). The control group consisted of 3 patients (n = 5) who did not have any signs of endometriosis. Molecular markers were visualized using the immunohistochemical method. Antibodies to tyrosine hydroxylase (TH, 1:200, Abcam, USA) and PGP 9.5 (PGP 9.5, 1:1000, Abcam, USA) were used as primary antibodies. Alexa Fluor 488 (1:1000, Abcam, USA) and Alexa Fluor 647 (1:1000, Abcam) were used as secondary antibodies. The results were visualized with a confocal microscope (FluoView1000 (Olympus)). 3D shooting was used to assess the reciprocal location of the studied markers. As a result of this work, it was found that the expression of both of studied markers was detected in all samples. The obtained data can significantly increase the understanding of the functioning mechanisms of the neoneurogenesis processes in ectopic and eutopic tissue, thereby allowing an increase in the accuracy of the endometriosis diagnostic methods.
Medical academic journal. 2019;19(1S):56-58
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THE CHARACTER OF SYSTEMIC CHANGES IN ADAPTIVE AND INNATE IMMUNE RESPONSE IN PATIENTS WITH MULTIPLE SCLEROSIS
Andreeva I.I., Sizyakina L.P., Goncharova Z.A.
Abstract
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.
Medical academic journal. 2019;19(1S):58-60
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PRURITUS AS A MARKER OF IMMUNE DISTURBANCES IN PSORIASIS
Barilo A.A., Smirnova S.V.
Abstract
Objective: Based on the study of some indicators of cellular and humoral immunity, evaluate the features of immunoreactivity in patients with psoriasis with concomitant pruritus. Materials and methods. Patients were examined with vulgar PS (n = 97), which were divided into 2 groups: group 1 - PS with pruritus (n = 73, mean age 40.0 ± 1.5 years), group 2 (comparison group) - PS without pruritus (n = 24, mean age 41.5 ± 2.7 years). The cellular immunity indicators was carried out by flow cytofluorimetry. Phagocytic activity of peripheral blood neutrophils was studied microscopically by the absorption of latex particles. Concentrations of immunoglobulins, cytokines, circulating immune complexes in the blood serum were evaluated by the method of enzyme-linked immunosorbent assay. Statistica 6.0 was used for statistical analysis. Our studies allowed us to identify features of PS with concomitant pruritus: severe clinical course of the disease with damage to the musculoskeletal system, associated with selective deficiency of class M immunoglobulins and increased activity of phagocytic neutrophils.
Medical academic journal. 2019;19(1S):60-61
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THE CONDITION OF CELLULAR IMMUNITY IN PATIENTS WITH OSTEOARTHROSIS BEFORE AND AFTER ENDOPROSTHESIS IMPLANTATION
Belova S.V., Gladkova E.V., Ulyanov V.Y., Zubavlenko R.A., Blinnikova V.V.
Abstract
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.
Medical academic journal. 2019;19(1S):62-63
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RELATIONSHIP OF NERVOUS AND IMMUNE SYSTEMS IN PATIENTS WITH CHRONIC MERCURY INTOXICATION
Bodienkova G.M., Lakhman O.L., Boklazhenko E.V., Kurchevenko S.I., Katamanova E.V.
Abstract
The purpose of the study was to identify the dependencies between the content of cytokines, neuronal antibodies and changes in the bioelectrical activity of the brain in patients with neurointoxication with mercury, depending on the severity of the pathological process. Surveyed men with professional chronic mercury intoxication I-II degree - 17 people and 33 - with ChMI III degree. The serum ELISA was used to determine IL-1β, IL-4, IL-8, IL-10, TNF-α, INF-γ, and AT to nerve tissue proteins (NF-200, GFAP, S-100, MBP, MAG, B-end. Ca-canal, B2GP, DNA, Glu-R, GABA-R, DA-R, Ser-R, AH-R). Visual evoked potentials were evaluated on an electroencephalograph. As a result of the research, the peculiarities of the relationship between cytokines and neuronal antibodies, indicating the initiation or regulation of immunopathological reactions depending on the degree of ChMI, were revealed. When ChMI I-II Art. IL-1β hyperproduction was accompanied by an increase in AT to Ser-R, B-head Ca-channel and a decrease in AT to Glu-R. In patients with ChMI III degree a decrease in IL-1β is associated with increased production of antibodies to S-100, and a decrease in TNF-α with increasing antibodies to NF-200, GABA-R, GFAP. In patients with ChMI with high levels of antibodies to S-100, a more pronounced delay in the appearance of the response of the cortex to the visual stimulus, an increase in the latency of P200 was revealed. Thus, the obtained data confirm the complex functional relationships between the nervous and immune systems, the selectivity and selectivity of damage to the structures of the nervous tissue at various stages of ChMI, which can serve as unique biomarkers.
Medical academic journal. 2019;19(1S):63-65
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Features of changes in the immune status and bioelectric activity of the brain in patients with asthma
Borukaeva I.K., Abazova Z.K.
Abstract
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.
Medical academic journal. 2019;19(1S):65-67
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THE LEVEL OF SYSTEMIC INFLAMMATION AND CHANGES IN ADAPTIVE IMMUNITY IN ALCOHOLIC PSYCHOSES
Didkovsky N.A., Malashenkova I.K., Ogurtsov D.P., Krynskiy S.A., Hailov N.A., Chekulaeva E.I., Mamoshina M.V., Ushakov V.L., Zakharova N.V., Kostyuk G.P.
Abstract
The aim of the work is to study the level of systemic inflammation and changes in adaptive immunity in the early period after acute psychosis to assess their participation in the pathogenesis of alcoholic mental and cognitive disorders. We examined 28 patients with alcoholic psychosis (AP) and a control group of 17 healthy volunteers. Indicators of systemic inflammation and immunity, including key cytokines and lymphocyte subpopulations, were investigated. After acute psychosis of patients with alcoholism, pronounced activation of humoral immunity with impaired clearance of immune complexes, increased content and activity of Th2 with signs of insufficiency and dysfunction of Th1, reduced content and activity of cytotoxicity system cells and signs of systemic inflammation (increased CRP, cortisol, cytokines). Activation of Th2 response and an excess of proinflammatory mediators in patients with AP through various ways of interaction with the Central nervous system (n. vagus, choroidal plexus of the ventricles, and others) can participate in the disorders of metabolism of neurotransmitters in the Central nervous system involved in the pathogenesis of alcoholism, and in the maintenance of neuroinflammation. A high level of systemic inflammation can be both a trigger of psychosis and a manifestation of violations of neuroimmune interactions, as well as the development of excitotoxicity and damage to neurons in acute psychosis.
Medical academic journal. 2019;19(1S):68-70
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Parameters of immunity and systemic inflammation in endogenous psychosis
Malashenkova I.K., Ogurtsov D.P., Krynskiy S.A., Hailov N.A., Chekulaeva E.I., Didkovsky N.A., Mamoshina M.V., Ushakov V.L., Morozova A.Y., Zakharova N.V., Kostyuk G.P.
Abstract
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.
Medical academic journal. 2019;19(1S):70-72
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INFLUENCE OF ENDOCRINE PATHOLOGY ON NEUROIMMOUNS INTERACTIONS IN PLACENTA
Drobintseva A.O., Andreev A.E., Makarenko S.V., Medvedev D.S., Soldatova Y.A., Polyakova V.O.
Abstract
According to statistics, approximately 75-80% of cases of diabetes mellitus in women during pregnancy show the presence of a urogenital infection in which the development of the inflammatory process is conducive to the elimination of the pathogen and the appearance of necrotic tissue. Such inflammatory processes, as a rule, occur with the participation of macrophages attracted by B-lymphocytes and NK-cells. The main goal of this study was to evaluate the expression ratio of immunocompetent cells: macrophages, NK cells and B lymphocytes in the placenta in women with diabetes mellitus who are in different age groups. Molecular markers were visualized using an immunoistochemical method. Were used antibodies to CD68 (1:300, Dako, USA) for macrophages, CD20 (1:300, Dako, USA) for B-lymphocytes and CD57 (1:300, Dako, USA) for natural killer cells. The results were visualized on a confocal microscope (FluoView 1000 (Olympus)). For scoring of microphotographs program “Morphology 5.2” was used. On the microphotographs the relative area of expression was evaluated, signified as the ratio of the area of the immunopositive reaction to the total area of the slide and the optical density. Then a statistical evaluation of the obtained data in the “Statistic 10.0” program was carried out. During the experiment, a sharp decrease in the expression of the CD68 marker in the placenta was detected. A decrease in the expression of the CD20 marker with an increase in the age of patients with diabetes mellitus was also demonstrated, while in healthy women an increase was observed in the middle age group. For natural killers, there was no difference between healthy and sick women. The result indicates a weakening of the reaction of the immune system in diabetes mellitus.
Medical academic journal. 2019;19(1S):72-74
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EXPERIMENTAL MODEL OF CFS: COGNITIVE, PHYSICAL AND METABOLIC CHARACTERISTICS OF PATHOLOGY DEVELOPMENT
Filatenkova T.A., Shanin S.N., Fomicheva E.E., Korneva E.A., Serebryanaya N.B.
Abstract
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.
Medical academic journal. 2019;19(1S):74-76
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NEUROIMMUNE MECHANISMS OF COGNITIVE IMPAIRMENT AT AFFECTIVE DISORDERS
Goldin B.G.
Abstract
The aim of this study was the identification of the neuroimmune mechanisms of cognitive impairment on the basis of investigation of an of cognitive disorders association with functional activity of blood mononuclear cells and the synthesis of tumor necrosis factor - α (TNF-α) in patients with affective disorders in the form of depressive reactions and depression.TNF-α expression level in blood mononuclear cells of patients conducted with using the reverse transcriptase polymerase chain reaction method. The proliferative activity of blood mononuclear cells was investigated by a standard method based on the inclusion of a radioactive label. Cognitive function was assessed on the basis of perception, memory, praxis, speech, and control function. The severity of affective symptoms was measured by the Hamilton scale. It was found that patients with depressive reactions were characterized by the mild non-elemental cognitive impairment; while, in patients with depression, more severe non-elemental cognitive impairments in the form of decreased attention, memory, and daily activity were observed. In patients with affective disorders in the form of depression, an increase in the synthesis of TNF-α in blood mononuclear cells was detected, both an increase of the expression frequency of its gene and an increase in mRNA level, as well as an increase of the proliferative activity of blood mononuclear cells, which indicates the presence of immune system dysfunction in this category of patients.Thus, in patients with depression, activation of the TNF-α synthesis in blood mononuclear cells occurs: an increase in the frequency of its expression and an increase of the level of mRNA; these changes are accompanied by the increasing of immune cells functional activity and moderate non-delicate cognitive disorder in the form of cognitive impairment.
Medical academic journal. 2019;19(1S):76-78
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THE COMPARATIVE STUDY OF HUMAN ENDOGENOUS RETROVIRUS HERV-E λ 4-1 EXPRESSION IN BLOOD IMMUNE CELLS OF MULTIPLE SCLEROSIS PATIENTS
Goldina I.A., Markova E.V.
Abstract
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.
Medical academic journal. 2019;19(1S):78-80
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IMMUNOLOGICAL CELULLAR-MOLECULAR MARKERS OF THE PERIPHERAL BLOOD OF А53Т MICE WITH GENETIC PREDISPOSITION TO PARKINSON’S DISEASE
Idova G., Alperina E., Zhanaeva S., Gevorgyan M., Tihonova M.
Abstract
The present experimental study aimed to find the most informative peripheral cellular-molecular immune markers, which can determine a risk of the development of Parkinson’s disease. The experiments were performed in transgenic mice of the A53T strain (2 months) characterized by an increased expression of alpha synuclein and genetically predisposed to Parkinson’s disease during aging. In comparison with the WT strain mice (control), A53T mice were found to have a reduced emotionality (increased horizontal motor activity and a significant decrease in defecation acts in the open field test) along with unchanged coordination and balance, tested using the Rotarod + hardware-software complex. These mice were also characterized by significant changes in the content of immune cell subpopulations in the peripheral blood - an increase in the percentage of CD3+T cells and CD3+4+T helper cells, a decrease in the content of CD19+B cells, with unaltered numbers of CD3+4+25+ 27-regulatory, CD19+25+B-regulatory cells and CD11b+115+monocytes. The percentage of T-regulatory cells expressing Toll-like receptors of the 2nd and 4th types (TLR2 and TLR4) was higher in A53T mice than in controls, while the number of cells expressing only TLR4 was reduced. The TLR2 expression did not differ between A53T and control mice. Analysis of the TLR2 and TLR4 expression on CD11b+115+monocytes has shown that the percentage of these cells with TLR4 was reduced in A53T mice compared to the control, while the content of cells with both TLR types did not depend on genotype. Proinflammatory cytokines (IL-6) prevailed over antiinflammatory (IL-10) in the supernatant of mononuclear blood cells of A53T mice suggesting the development of neuroinflammation.The study was supported by Russian Foundation of Basic Research (grant N18-015-00226 А).
Medical academic journal. 2019;19(1S):80-81
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NEUTROPHILS’ FUNCTIONAL STATE IN ALZHEIMER’S DISEASE
Ivanov P.A., Shmakova A.A., Mikhailova N.M.
Abstract
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.
Medical academic journal. 2019;19(1S):81-82
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INTERACTION OF IMMUNE AND NERVOUS SYSTEMS WHEN USING PCL SCAFFOLDES IN MAXILOFACIAL SURGERY
Kosyakova G.P., Muslimov A.A., Lysenko A.I.
Abstract
An important parameter of scaffold matrices is biocompatibility. Biocompatibility assessment is carried out in several stages. At the first stage, its compatibility with in vitro cell cultures is determined. At the second in vivo stage, biocompatibility is assessed by examining histological preparations of tissue biopsies obtained from the area of implantation of scaffolds in experimental animals. Therefore, the following tasks are set: to determine the immunological compatibility of the blood cells of rabbits during the surgical introduction of scaffolds and to evaluate the nervous stress during operations. In our studies, the pcl scaffolds presented are polymeric biodegradable matrices that are polycaprolactone and polyhydroxybutyrate. Capsules consist of polypeptides and polysaccharides, the shell of which is coated with a layer of silicate nanoparticles.
Medical academic journal. 2019;19(1S):82-84
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IMMUNOLOGICAL MARKERS OF LONG-TERM EFFECTS OF TREATMENT IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT
Krynskiy S.A., Malashenkova I.K., Hailov N.A., Ogurtsov D.P., Chekulaeva E.I., Ponomareva E.V., Gavrilova S.I., Didkovsky N.A.
Abstract
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.
Medical academic journal. 2019;19(1S):84-86
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Cellular mechanisms of neuroimmune interaction in multiple sclerosis: ionotropic glutamate receptors of T-lymphocytes
Kuzmina U.S., Bakhtiyarova K.Z., Vakhitova Y.V.
Abstract
Using flow cytometry and real-time RT-PCR, we studied the effect of the blockade of glutamate NMDA receptors on the quantitative distribution of IFNγ- and IL-4-producing CD4+ and CD8+ T-lymphocytes and the expression of transcription factor of genes T-bet and GATA-3 in immune cells derived from healthy individuals and multiple sclerosis patients (MS). From the results of the study, it follows that blockade of NMDA receptors leads to a decrease in the proportion of studied effector subpopulations of T-lymphocytes, as well as differential modulation of gene expression of transcription factors (TBX21, GATA3). The severity of the negative effect of receptor blockade differs in different subpopulations of CD4+ and CD8+ T cells, which leads to a shift in the cytokine balance towards “proinflammatory” type 1 T-cells, to a greater extent in patients with MS. Thus, glutamate can regulate the Th1/Th2 and Tc1/Tc2 сytokine balance by modulating the activity of NMDA receptors of T lymphocytes in MS.
Medical academic journal. 2019;19(1S):86-88
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INFLAMM-AGING: THE HYPOTHESIS OF THE INFLAMMATION ROLE IN ALZHEIMER DISEASE PROGRESS
Kventoy I.M., Linkova N.S., Diatlova A.S., Zuev V.A., Kventaia T.V.
Abstract
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.
Medical academic journal. 2019;19(1S):88-91
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PRESERVED NUMBER OF OREXIN NEURONS IN POSTMORTEM HYPOTHALAMIC TISSUE OF CHRONIC ALCOHOLICS
Kudriavova A.S., Meskenaite V., Mikhailov V.I., Schesny M., Korneva E.A., Gavrilov Y.V., Valko P.O.
Abstract
The hypothalamic orexin system is critically involved in addiction, including chronic alcohol abuse. Microinjection of orexin into the lateral hypothalamus increases alcohol intake in rats, while reduced immunoreactivity of orexin neurons is associated with decreased alcohol drinking. Recently, the numbers of orexin neurons were found to be increased in opiate addiction in humans [4] and cocaine addiction in rats [2], but the integrity of orexin neurons has not yet been studied in human alcoholics. We examined the hypothalamus of 9 patients of chronic alcoholism and 10 subjects without a history of alcoholism or any other neurological or psychiatric disorder. We performed immunohistochemistry for orexin A, followed by stereological quantification. The hypothalamic tissue of chronic alcoholics exhibited a slightly increased number (9%) of orexin-containing neurons compared to the control group (123’087 ± 18’536 and 110’431 ± 14’439, p = 0.11). Mean Gundersen’s coefficient of error was 0.06 ± 0.01. The number of orexin neurons was similar in chronic alcoholics and control subjects without a history of alcoholism. Further examination of alcohol-induced hypothalamic damage is needed to understand, whether a neuroplastic increase in orexin neurons counterbalances a concurrent alcohol-toxic damage to these neurons.
Medical academic journal. 2019;19(1S):91-92
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GASTROINTESTINAL DYSFUNCTIONS AND PERIPHERAL INFLAMMATORY CYTOKINES IN PARKINSON’S DISEASES
Miliukhina I.V., Ermolenko E.I., Ivanova A.S., Gracheva E.V., Kotyleva M.P., Agapova E.A., Suvorov A.N.
Abstract
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.
Medical academic journal. 2019;19(1S):93-94
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NEUROIMMUNE PATTERN IN THE COMORBIDITY BETWEEN DEPRESSION AND ALCOHOL USE DISORDER
Nevidimova T.I., Davydova T.V., Vetrile L.A., Savochkina D.N., Zakharova I.A., Galkin S.A.
Abstract
The aim of the study is to search for biomarkers of risk and prevention of the formation of alcohol dependence on the background of depression. Antibodies are evaluated for a number of neurotransmitters, the information content of which is confirmed by preliminary studies. Materials and methods. Autoantibodies to dopamine, norepinephrine, 5-hydroxytryptamine, glutamate, gamma-aminobutyric acid were determined by ELISA in 60 controls and patients with depression and alcohol use disorder (AUD). Results. The level of antibodies to all studied neurotransmitters decreases with depression, especially complicated by alcoholism. An exception is the level of antibodies to serotonin, which increases with AUD and depression combined with AUD. Conclusion. It is assumed that this type of reaction may be a biomarker of the risk of alcoholism in depression.
Medical academic journal. 2019;19(1S):94-96
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ESPECIALLY CELLULAR IMMUNITY IN PATIENTS WITH TRAUMATIC BRAIN INJURY OF DIFFERENT SEVERITY IN ACUTE PERIOD
Norka A.O., Kuznetsova R.N., Kudryavtsev S.V., Kovalenko S.N., Serebriakova M.K., Vorobyev S.V.
Abstract
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.
Medical academic journal. 2019;19(1S):96-98
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THYMIC STRESS-INDUCED ATROPHY AND MAST CELLS
Polevshchikov A.V., Gusel’nikova V.V.
Abstract
In a study using histological methods, the dynamics of thymic mast cells was evaluated in response to the administration of hydrocortisone to white outbred mice. It was established that 48 hrs after the administration of the hormone, the number of mast cells increases 10-fold, while cells appear at all stages of maturation. In parallel, the level of mast cell degranulation increases. Maturation of mast cells within the thymus and their participation in the regulation of cell migration and remodeling of the extracellular matrix under stress is assumed.
Medical academic journal. 2019;19(1S):98-100
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ENDURANCE OF RATS WITH DISBIOZ IN EMOTIONAL-PHYSICAL STRESS
Safonova A.F., Krylova I.B., Shemerovsky K.A.
Abstract
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.
Medical academic journal. 2019;19(1S):100-101
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IMPACT OF AGING ON THE DEVELOPMENT OF NEUROIMMUNE DEFICIENCIES AFTER EXPERIMENTAL MILD TRAUMATIC BRAIN INJURY (TBI)
Serebryanaya N.B., Shanin S.N., Filatenkova T.A., Fomicheva E.E.
Abstract
Patient’s age affects the course of posttraumatic inflammation and recovery after TBI. The goal of the research was to identify the differences in neuroimmune deficiencies in young and old animals after experimental TBI. The research was carried out using male Wistar rats aged 3 and 18 months. Mild TBI was caused by weight drop TBI model. A group of animals was injected abdominally with 30 mkg/kg recombinant human interleukin-2 (Ronkoleukin, Biotech) daily for three days, starting 72 hours after TBI. The control group consisted of intact animals and rats who did not receive rIL-2 prior to TBI (n = 5 for both groups). The results obtained have shown that old animals after mild TBI had different testosterone and proliferative activity levels than the young ones; the injection of rIL-2 led to an increase in neurotrophic factors (testosterone and BDNF) without causing additional activation of lymphocytes.
Medical academic journal. 2019;19(1S):102-103
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EFFECTS OF INTRANASAL BACTERIAL ENDOTOXIN ADMINISTRATION ON EXPRESSION OF ALPHA-SYNUCLEIN IN PERIPHERAL STRUCTURES OF THE OLFACTORY SYSTEM
Sergeyeva T.N., Sergeyeva K.S.
Abstract
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.
Medical academic journal. 2019;19(1S):103-104
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EXPERIMENTAL INTESTINAL DYSBIOSIS IN RATS INCREASES THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER AND INDUCES NEUROINFLAMMATION
Sergeyev V.G., Sergeyeva T.N.
Abstract
The mammalian intestinal microbiota consists of bacteria, fungi and viruses, including bacteriophages. This complex ecosystem has dynamic stability. It is assumed that changes in the composition of the microbiota can cause intestinal barrier dysfunction and the development of a number of pathologies, including neurodegenerative diseases accompanied by neuroinflammation. The molecular and cellular mechanisms underlying such a relationship remain poorly understood. We hypothesized that bacteriophages cause intestinal dysbiosis, increased intestinal permeability and local inflammation. Bacterial factors (endotoxins, zonulin-like proteins) and local inflammation products (cytokines, alpha-synuclein protein) can enter the circulation and increase the permeability of the blood-brain barrier (BBB), which will cause neuro-inflammation and damage to neurons. In this study, we observed an increase in BBB permeability and induction of neuroinflammation in the brain after rectal administration of a bacteriophage cocktail (Microgen, Russia). The permeability of the BBB was judged by the volume of the vital dye (Evans blue) emerging from the bloodstream into the brain parenchyma, and the development of the neuroinflammatory response by increasing the number of immunohistochemically stained microglial and astroglial cells.
Medical academic journal. 2019;19(1S):104-105
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BRAIN CELLS REACTION IN A RESPONSE TO ANTIGEN INJECTION IN ANIMALS EXPOSED TO ACUTE PRENATAL STRESS
Shakleina P.S., Novikova N.S.
Abstract
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.
Medical academic journal. 2019;19(1S):105-107
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IMPACT OF RONCOLEUKIN (RIL-2) ON THE LYMPHOCYTE-TRIGGERING ACTIVITY OF MACROPHAGES AFTER TRAUMATIC BRAIN INJURY IN VARIOUSLY AGED RATS
Shanin S.N., Serebryanaya N.B., Filatenkova T.A., Fomicheva E.E.
Abstract
IL-1β is involved in both brain damage process and the mechanisms of brain regeneration processes. The goal of the present research is to measure the change in the production of lymphocyte-activating factor (LAF) after experimental traumatic injury (TBI) in variously aged rats and evaluate the possibility to correct LAF production with roncoleukin (rIL-2). LAF activity in the supernatants of peritoneal macrophages of injured rats was measured by its ability to have comitogenic effect on the proliferation of rat thymocytes stimulated by suboptimal lectin doses. LAF stimulation index was defined as ratio of stimulated to unstimulated levels of LTF. Results and discussion. The strongest suppression of microphages’ cytokine-producing function was found in older rats after TBI. rIL-2 injection significantly reversed the injuries caused by TBI even in older rats. These data confirm that exogenic IL-2 is able to activate the functional characteristics of innate immunity cells and that is has a normalizing effect on the immune cells of the older animals.
Medical academic journal. 2019;19(1S):107-108
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ALTERATIONS IN THE MRNA EXPRESSION OF D2 DOPAMINE RECEPTOR SPLICE VARIANTS AS POSSIBLE MECHANISM OF PREFRONTAL DYSFUNCTION AFTER EARLY-LIFE IMMUNE CHALLENGE
Schwarz A.P., Trofimov A.N., Ischenko A.M., Zubareva O.E., Klimenko V.M.
Abstract
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.
Medical academic journal. 2019;19(1S):109-111
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THE LATENT OF RHINOSINUSITIS AS A MANIFESTATION OF NEURO-IMMUNE INTERACTIONS
Stagniyeva I.V., Stateshnaya P.A.
Abstract
Purpose: to determine the role of a pain symptom in the diagnosis of rhinosinusitis on the background of immune deficiency. 240 patients with rhinosinusitis without pain symptom were divided into 3 groups: group 1 - patients with acute viral rhinosinusitis (AVRS), group 2 - patients with acute bacterial sinusitis (ABRS), group 3 (n = 32) - control. All patients underwent a complete otorhinolaryngological examination, assessment of the pain symptom, an immunogram, the level of SP in the blood serum. At SP > 100 pg/ml in group 1, the change in indicators was typical for viral infection, in group 2, for bacterial infection. With an SP < 100 pg/ml, the cytokine balance is predominantly biased towards anti-inflammatory cytokines, and the direction of differentiation of Th-1/Th-2 lymphocytes towards the Th-2 pathway, which is manifested by immune deficiency, which leads to severe or prolonged course of the disease, which may indicate impaired neuro-immune interactions.
Medical academic journal. 2019;19(1S):111-112
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LABORATORY INDICATORS OF DIABETIC POLYNEUROPATHY
Stepanova T.V., Popyhova E.B., Ivanov A.N.
Abstract
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.
Medical academic journal. 2019;19(1S):112-114
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PERIPHERAL BLOOD TH17 SUBSETS IN PATIENTS WITH MULTIPLE SCLEROSIS
Kudryavtsev I.V., Petrov A.M., Ilves A.G., Mineev K.K., Serebriakova M.K., Stolyarov I.D.
Abstract
Using multicolor flow cytometry four main Th17 subsets were identified within total CCR6-expressing Th cell in peripheral blood from patients with multiply sclerosis (MS, n = 26) and healthy control subjects (HC, n = 44). MS showed significantly higher frequencies of CCR6+DP and “classical” Th17 subsets, while the level of Th17.1 was significantly decreased if compared to HC. Correlation analysis revealed a significant relationship between the decrease of CCR6+DN Th17 subset and EDSS worsening (r = -0.456, p = 0.022). The area under the ROC curve (AUC) for the percentage of “classical” Th17 within CCR6+ Th as a predictor of MS was 0.948 (0.882 to 1.014, p < 0.001) and for Th17.1 cells - 0.937 (0.863 to 1.011, p < 0.001). The optimal cutoff value for percentage of “classical” Th17 for predicting MS was 31.55% within CCR6+ Th cells with 88.0% sensitivity and 95.45% specificity, while for Th17.1 - 38.66% within CCR6+ Th cells with 88.0% sensitivity and 95.45% specificity. Our data indicate that the relative numbers of “classical” Th17 and Th17.1 within CCR6+ Th cells were effective in discrimination between MS and HC groups.
Medical academic journal. 2019;19(1S):114-116
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THE EFFECT OF CHEMOKINE CXCL-13 ON THE CLINICAL AND FUNCTIONAL STATUS OF PATIENTS WITH MULTIPLE SCLEROSIS IN REMISSION
Sursiakova N.V., Kuklina E.M., Baidina T.V., Nekrasova I.V.
Abstract
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.
Medical academic journal. 2019;19(1S):117-119
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DELAYED COGNITIVE DEFICIT AS A RESULT OF NEONATAL LIPOPOLYSACCHARIDE EXPOSURE: A PRESUMABLE IMPLICATION OF LONG-LASTING CHANGES OF NEUROPLASTIC GENE EXPRESSION
Trofimov A.N., Zubareva O.E., Schwarz A.P., Veniaminova E.A., Fomalont K., Klimenko V.M.
Abstract
Disorders of the CNS development at an early age caused by various types of perinatal pathology, such as infectious diseases, trauma, hypoxia and ischemia, often lead to the development of cognitive brain dysfunctions in adulthood. Proinflammatory cytokines play key role in these pathological processes and can affect the expression of genes involved in the regulation of neuroplasticity. This article describes the changes in the expression of fibroblast growth factor-2 (Fgf2), as well as genes encoding matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), proteins that by intercellular matrix re-modeling are involved in the regulation of neuroplasticity.
Medical academic journal. 2019;19(1S):119-120
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ASSESSMENT OF HUMORAL IMMUNITY IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B, COMBINED WITH CHRONIC NON-CALCULOUS CHOLECYSTITIS
Yakimovich S.E.
Abstract
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.
Medical academic journal. 2019;19(1S):121-122
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FEATURES OF FUNCTIONING OF THE IMMUNE SYSTEM UNDER STRESS
Zaitseva N.S., Syziakina L.P.
Abstract
The psychobiological essence of stress is to reprogram the resources of the human body for survival in extreme life-threatening conditions. The study of the activity of the main homeostatic systems in acute and prolonged adaptive reactions in soldiers is of great scientific and practical interest. The immune status was assessed in 42 military officers who participated in special operations for the first time. Not only quantitative, but also structural changes of the immune system function in the military-participants of special operations were revealed. The results require further analysis, study and consideration in assessing the health of soldiers.
Medical academic journal. 2019;19(1S):123-124
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PRENATAL STRESS IN PROGRAMMING OF IMMUNE AND NEUROENDOCRINE SYSTEM DEVELOPMENT
Zakharova L.A.
Abstract
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.
Medical academic journal. 2019;19(1S):124-126
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Features of the dynamics of inflammation and apoptosis markers in patients with different acute post-stroke period
Zozulya S.A., Otman I.N., Chukanova A.S., Klyushnik T.P.
Abstract
The purpose of this was to study the dynamics of markers of inflammation and apoptosis in the serum of patients with ischemic stroke in the early post-stroke period. Materials and methods. The study involved 22 patients (mean age 60 ± 5.5 years) with different dynamics of neurological symptoms in the acute post-stroke period. Patients were examined twice: on the 1st and 10th day of observation. Quantitative assessment of the severity of neurological deficit using ESS and NIHSS scales was carried. Enzymatic activity of leukocyte elastase, functional activity of a1-proteinase inhibitor, level of autoantibodies to MBP (inflammatory markers), as well as the content of p53 and Bcl-2 proteins (markers of apoptosis) were determined in serum. The control group consisted of 35 somatically healthy people of the appropriate age and sex. Results. Identified the different features of the spectrum of the analyzed markers of inflammation and apoptosis in patients with positive and negative dynamics of neurological symptoms in the acute period of ischemic stroke assessed according to the ESS and NIHSS scales. The observed clinical and biological relationships reflect the features of the course of the early post-stroke period and can be considered as possible predictors of the development trajectory of acute brain ischemia.
Medical academic journal. 2019;19(1S):126-129
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The relevance of cytokine indicators in the hemorrhagic transformation development of cerebral infarction risk measuring
Nikiforova T.A., Doronin B.M., Peskov S.A.
Abstract
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.
Medical academic journal. 2019;19(1S):129-132
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STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF MICROGLIA IN THE POSTNATAL RAT STRIATUM
Antipova M.V., Guselnikova V.V., Korzhevskii D.E.
Abstract
The aim of this study was to evaluate the morphological and functional characteristics of microglial cells in the rat striatum at different stages of postnatal development. Using immunocytochemical methods and fluorescent microscopy, brain sections were analysed at each of the following postnatal ages: day 7 (n = 4), day 14 (n = 3), 4 to 6 months (n = 3). Different morphological and functional types of microglial cells were identified and characterized in details. It was noted that microglia activated during normal brain development do not contain vimentin, which is characteristic of stroke-activated microglia.
Medical academic journal. 2019;19(1S):133-134
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MICROGLIA AND ASTROCYTES OF THE HUMAN BRAIN SUBSTANTIA NIGRA
Korzhevskii D.E., Sufieva D.A., Brovko M.A.
Abstract
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.
Medical academic journal. 2019;19(1S):135-135
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THE OUTCOME OF CEREBRAL PATHOLOGY BY THE END OF THE FIRST YEAR OF LIFE IN NEWBORN BABIES WITH CYTOMEGALOVIRUS INFECTION
Kravchenko L.V.
Abstract
Objective: to study costimulatory molecules (CD28, CD40) on lymphocytes of the peripheral blood in newborn babies with CMVI and to determine prognostic indices of the cerebral pathology outcome by the end of the first year of life.We examined 114 children at the age of three months, who had CMVI during neonatal period. In 37 children neurological symptoms remained by the end of the first year of life. At 37 children the neurologic symptomatology by the end of the first year of life remained: delay of psychomotor development (44.8%), deafness (5.9%), epilepsy (11.9%), spastic tetraparesis (32.2%) blindness (13.4%). At 77 children was absent neurologic symptomatology by the end of the first year of life.A control group was comprised of 15 healthy newborns. The content of lymphocytes, expressing CD28, CD40, CD3+, CD4+, CD28+, CD20+, was determined using laser flow cytofluorometer “Beckman COULTER” Epics XL II (USA) by means of monoclonal antibodies to the clusters of differentiation CD3+, CD20+, CD4+, CD28+, CD40+ of IMMUNOTECH Company (France).The analysis of multidimentional nonlinear dependencies was performed using PolyAnalist 3.5. Pro package. The formula of the forecast of preservation of neurologic symptomatology is calculated.((CD3-CD28+ * 0.074) + CD4+ * (-0.182) + (CD3+CD28- * 0.035) + CD40 * (-0.2862) + CD3 * 0.1062) + + (CD28 * 0.1952)) - 0.4588.If the result of the calculation according to the formula is > 0.39, than a child will have brain damages by the end of the first year of life. Sensitivity - 71.43%, specificity - 88.89%. The likelihood ratio of the positive result is 13.5.The determination of CD3+T-lymphocytes, lymphocytes, expressing CD28 in the total population, T-lymphocytes without the costimulatory marker CD28 (CD3+CD28-) and also B-lymphocytes, expressing CD40 on their surface, is significant for the prognosis of neurological symptomatology preservation by the end of the first year of life.
Medical academic journal. 2019;19(1S):136-137
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SEROTONIN LEVEL IN PERIPHERAL BLOOD AND THE BRAIN’S BIOELECTRICAL ACTIVITY IN YOUNG PEOPLE 15-17 YEARS
Krivonogova E.V., Poskotinova L.V., Demin D.B., Stavinskaya O.A.
Abstract
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).
Medical academic journal. 2019;19(1S):137-138
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IMMUNOGENESIS IN THE DESTRUCTION OF CELLS OF THE NERVOUS SYSTEM UNDER THE INFLUENCE OF THE RABIES VIRUS
Grin S.A., Pukhova N.M., Matveyeva I.N., Samuylenko A.Y., Melnik R.N.
Abstract
The nature of rabies immunity is not well understood, the zones of deployment of protective mechanisms are unknown, and the place where antibodies meet with the virus is unclear. The issue of the mechanism of protection of the central nervous system against rabies virus is relevant. It has been hypothesized that protection (immunity) of the central nervous system to the rabies virus is induced by the distant interaction of antibodies on the nerve сells and is mediated by the energy-information field of specific antibodies circulating in the blood vessels of the central nervous system. To confirm this hypothesis, the non-contact effect of rabies antibodies on the rabies virus (strain “Shchelkovo-51”) in the culture cell (BHK-21/13) and the decrease in antigen accumulation from 1.7 to 2.9 times were experimentally shown. The obtained data confirm the main point of the hypothesis on the protection of the central nervous system against the rabies virus using an energy-information biofield.
Medical academic journal. 2019;19(1S):139-141
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IMMUNE RESPONS OF CYTOKINES IN DIFFERENT COURSE OF VIRAL ENCEPHALITIS IN CHILDREN
Skripchenko N.V., Ivanova G.P., Skripchenko E.Y., Zheleznikova G.F.
Abstract
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.
Medical academic journal. 2019;19(1S):141-143
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REGULATION OF MICROCIRCULATION DURING REMODELING OF SKIN SCAR UNDER INFLUENCE OF LASER
Astakhova M.I., Golovneva E.S., Astakhova L.V., Astakhov I.A., Ignatieva E.N.
Abstract
An experimental study was fulfilled on 15 laboratory mail rats. After normotrophic skin scar modeling, the scar tissue was once exposed to high-intensive red, near or far infrared laser in comparable modes. Microcirculation parameters were assessed with laser Doppler flowmetry. It was found that the nature of microcirculation response to high-intensive laser irradiation substantially depended on the laser wavelength and its penetrating depth. Laser resurfacing of the skin scar with CO2 laser in early period led to blood stasis in the vessels and decrease in the vascular wall tone against the background of sympathetic influence increase. The red and near-infrared lasers caused the increased arterial blood inflow and venular outflow, with local regulation by myogenic tone prevailing.
Medical academic journal. 2019;19(1S):144-145
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THE INFLUENCE OF LASER RADIATION ON VEGF EXPRESSION IN THYROID TISSUE IN EXPERIMENTAL HYPOTHYROIDISM
Golovneva E.S., Smelova I.V.
Abstract
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.
Medical academic journal. 2019;19(1S):145-146
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FEATURES OF MAST CELL RESPONSE AND VEGF EXPRESSION IN THE SKIN DEPENDING ON THE POWER OF LASER EXPOSURE
Kudrina M.G., Golovneva E.S., Astakhova L.V., Kravchenko T.G., Ignatieva E.N., Yelovskikh I.V.
Abstract
The aim of the work was to study the dynamics of morphofunctional reactions of mast cells and VEGF expression in the skin of rats after infrared 970 nm laser exposure with 1.0, 3.0 and 5.0 W power. Removal of animals from the experiment was carried out 1 hour and 1 day after irradiation. The significant increase in mast cells degranulation index in the abdominal skin was noted 1 hour after irradiation with the increase in power from 1 to 5 W and as compared with the control. The study showed the VEGF expression increase in the dermis 1 hour after 1 W power irradiation and in the subepidermal, dermal and hypodermal layers 1 day after the irradiation compared with the control. When using 3 W and 5 W laser irradiation, an increase in VEGF expression was observed in all layers of the abdominal skin both for 1 hour and for 1 day in comparison with the control. Since mast cell degranulation and VEGF expression are higher after 3 and 5 W infrared laser irradiation, these parameters are preferable for stimulating microcirculation in the skin.
Medical academic journal. 2019;19(1S):146-147
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MSCs ARE LOCATED IN THE PERINEURIUM OF THE RECIPIENT RAT AFTER ALLOTRANSPLANTATION INTO DAMAGED NERVE
Petrova E.S., Isaeva E.N., Kolos E.A., Korzhevskii D.E.
Abstract
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.
Medical academic journal. 2019;19(1S):148-148
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EDITING THE BEHAVIOR OF EXPERIMENTAL ANIMALS MODULATED IN VITRO BY IMMUNE CELLS
Knyazheva M.A., Serenko E.V., Karpovich G.S.
Abstract
The aim of the study is to edit the hyperactive behavior in experiments using immunocyte transplantation using in vitro modules with neuroleptic functional activity. Materials and methods. Experimental model: male mice (CBAxC57Bl/6) F1 of three months of age with hyperactive behavior. Immune cells were treated with chlorpromazine in a test tube, injected intravenously into the recipient, in which the behavior parameters in the open field test and the cytokine content in the brain were determined by ELISA. Results. Transplantation of precision and neuroleptic components contained in recipient mice is accompanied by a decrease in the indices of research and motor components, as well as the levels of IL-1β, IL-6 and TNFα cytokines in the brain.
Medical academic journal. 2019;19(1S):149-151
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INTEGRAL ADAPTATION RESPONSE OF THE BODY EXPOSED TO A BROADBAND STOCHASTICALLY ORGANIZED ELECTROMAGNETIC RADIATION TO A LOCALIZED PROCESS OF FORMALIN-INDUCED EDEMA CAUSING NEUROGENIC PAIN
Shikhlyarova A.I., Zhukova G.V., Goncharova A.S., Bragina M.I., Zhadobina A.A., Protasova T.P., Lukbanova E.A.
Abstract
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.
Medical academic journal. 2019;19(1S):151-152
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THE AUTONOMIC NERVOUS SYSTEM IN THE CORRECTION OF FUNCTIONAL DISORDERS OF THE SMALL INTESTINE IN THE COMPLEX TREATMENT OF EXPERIMENTAL ETHANOL INTOXICATION
Sluchanko E.I.
Abstract
The work is devoted to fundamental medical and biological studies, which make it possible to understand the basic laws of photobiology, part of which is super venous laser irradiation of blood. Neurohistochemical, histochemical, and electrophysiological methods were studied in the Wistar rats morphofunctional state of the small intestine under the influence of the supravenous laser blood irradiation in the complex treatment of experimental ethanol intoxication.The importance of the autonomic nervous system in the understanding of the characteristics of the effect of superluminal laser irradiation of blood on biological tissues in the complex treatment of experimental ethanol intoxication is emphasized. Experimental pathogenetically justified use of laser stimulation initiates the activation of adaptive processes, which is reflected in the restoration of the motor function of the small intestine on the 3rd day after the treatment of ethanol intoxication. The changes observed by us under the influence of supravenous laser irradiation of blood can be estimated as a state of increased activation of autonomous regulatory systems of the small intestine. Normalization after the use of supravenous laser irradiation of blood imbalance of neuromediation in the tissues of the small intestine, the increased activity of the enzymes of the aerobic cycle in the muscular layer of the named intestine is a consequence of adaptive changes, which is reflected in the restoration of the motor function of the small intestine with ethanol intoxication.
Medical academic journal. 2019;19(1S):153-155
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Candida brain damage on the background of HIV-infection
Uliukin I.M., Bulygin M.A., Bulankov Y.I., Orlova E.S.
Abstract
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.
Medical academic journal. 2019;19(1S):156-158
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THE CORTICOSTATIC EFFECT OF HUMAN LACTOFERRIN DEPENDS ON THE AMINO ACID COMPOSITION OF THE N-TERMINUS OF THE MOLECULE
Aleshina G.M.
Abstract
The effect of various structural variants of human lactoferrin on stress-induced changes in the corticosterone level in the blood in rats was studied. A model of combined emotional and physical stress - swimming in cold water (1-4 °C) for 2 minutes. The level of corticosterone in plasma was determined by enzyme immunoassay. We have previously found that preventive intraperitoneal administration of native lactoferrin reduces the stress-induced increase in corticosterone concentration in the blood of rats 30 minutes after stress. This work shows that transgenic human lactoferrin, which lacks four arginine residues at the N-terminus, does not have this effect. The obtained results allow us to conclude about the key role of N-terminal amino acid residues in the implementation of the corticostatic activity of lactoferrin.
Medical academic journal. 2019;19(1S):159-160
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ANTIMICROBIAL ACTIVITY OF LYSOZYME TOWARDS LISTERIA MONOCYTOGENES AT VARIOUS MEDIUM CONDITIONS
Berlov M.N., Legkovoy S.V., Umnyakova E.S., Kokryakov V.N.
Abstract
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.
Medical academic journal. 2019;19(1S):161-162
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USING SEQUENCE PATTERNS TO IDENTIFY AND DESIGN NEW ANTIMICROBIAL PEPTIDES
Eliseev I.E., Terterov I.N., Shamova O.V.
Abstract
Natural antimicrobial peptides (AMPs) are remarkably diverse, yet they all share some common structural and functional features. In an attempt to find what determines similar activities of non-homologous molecules, we performed a comprehensive analysis of sequence patterns in AMPs. We found that natural AMPs possess characteristic sequence patterns, and these patterns differ for peptides with α-helical and β-sheet structure. We showed that the patterns facilitate computational identification of AMPs in databases. We then used patterns to design new peptides, synthesized them and assayed for antibacterial activity. The most active among synthetic peptides exhibited activity against Gram(+) and Gram(-) pathogens comparable to best natural AMPs.
Medical academic journal. 2019;19(1S):162-164
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THE EFFECT OF THYMOSIN β4 ON THE FUNCTIONAL ACTIVITY OF THE IMMUNE AND NERVOUS SYSTEM COMPONENTS
Ivanova V.P.
Abstract
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.
Medical academic journal. 2019;19(1S):164-166
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THE EFFECT OF KE PEPTIDE ON THE TELOMERE LENGTH OF PHA-STIMULATED HUMAN LYMPHOCYTES
Khavinson V.K., Linkova N.S., Pendina A.A., Efimova O.A., Koltsova A.S., Krapivin M.I., Tikhonov A.V., Petrova L.I., Petrovskaia-Kaminskaia A.V., Baranov V.S.
Abstract
The goal of the research is to study the effect of KE peptide on telomere length of PHA-stimulated blood lymphocytes of young and middle-aged men. 11 blood lymphocyte samples were enrolled in the analysis. Relative telomere length was measured using fluorescence in situ hybridization with DNA-probes specific to telomere sequences of human chromosomes. 5 cases of significant telomere length alteration were registered. These changes were more frequent registered in middle-aged people: 4 invents cases versus 1. KE peptide increased telomere length in blood lymphocytes of middle-aged people if it was basically low and, vice versa, decreased the basically high telomere length.
Medical academic journal. 2019;19(1S):166-168
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CHEMICAL SYNTHESIS AND ANALYSIS OF ANTIMICROBIAL AND HEMOLYTIC ACTIVITY OF STRUCTURAL ANALOGOUS OF A PEPTIDE PROTEGRIN 1
Kopeykin P.M., Sukhareva M.S., Lugovkina N.V., Shamova O.V.
Abstract
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.
Medical academic journal. 2019;19(1S):169-170
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STRESS-PROTECTIVE ACTION OF THYMUS PEPTIDES CONCERNING AGING RATS
Korolev A.G., Novoseletskaya A.V., Kiseleva N.M.
Abstract
The survey objective is to check stress-protective action of thymus peptides concerning aging rats, experimentally. Methods used to study anxiety state were applied in tests with 18-months rats. It was found that thymus peptides in elevated plus maze (Thymosin fration 5 (0.5 mg/kg) and Thymulin (0.15 mg/kg)), and anxiolytic Diazepam (0.5 mg/kg) increased the motion activity in open arms, and number of positions onto hind legs in the light part of dark-light chamber. Influence of thymus peptides on the emotional stress associated with the failure of formated conditioned response of active avoidance was studied among aging rats. Within the control the failure caused a sharp decline in avoidance reactions and other demonstration of emotional tension. Thymus peptides and Diazepam prevented negative consequences on avoidance learning reactions. Thus, thymus peptides have demonstrated effect comparable to Diazepam in used models conditions. In avoidance learning model thymus peptides entirely prevented the consequences of emotional stress in ageing rats.
Medical academic journal. 2019;19(1S):170-172
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PROBABLE ANALGESIC EFFECT OF SYNTHETIC TETRAPEPTIDE
Plakhova V.B., Penniyaynen V.A., Rogachevskii I.V., Podzorova S.A., Merculova E.A., Krylov B.V.
Abstract
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.
Medical academic journal. 2019;19(1S):172-174
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COMPARATIVE EFFECT OF KE AND EW PEPTIDES ON NORMAL AND TUMOR IMMUNE CELLS
Linkova N.S., Mironova E.S., Ivko O.M., Orlova O.A., Dudkov A.V.
Abstract
KE and EW peptides have an immunoprotective and oncostatic effect in experimental studies. However, their comparative effect on normal and cancer immune cells has not been carried out yet. The aim of the work is to study the effect of KE and EW peptides on T-lymphocytes and Berkitt lymphoma cells growth in culture. To plot the cell growth curve, the cells were scattered at a concentration of 20,000 per 2 ml. KE and EW peptides were added to cultures at 100 ng/ml. Counting cells was carried out in the Gorjaev’s chamber. KE and EW peptides increased the number of lymphocytes of human blood as compared with the control during 5 days by 64-219%. KE and EW peptides reduced the number of Burkitt lymphoma cells as compared with the control during 5 days by 37-101%. KE and EW peptides decreased tumor immune cell proliferation and increased normal human lymphocytes grow. We suppose, that these effects can be connected with various ways of peptide regulation of methylation status of DNA.
Medical academic journal. 2019;19(1S):174-176
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PREDICTORS OF EFFECTIVE USE OF T CELL MIMETICS IN IMMUNE AND ENDOCRINE DISORDERS TREATMENT
Luybimov D.S., Britanov A.N.
Abstract
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.
Medical academic journal. 2019;19(1S):176-178
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BACTENECINS AS CELL-PENETRATING PEPTIDES
Shamova O.V., Nazarov A.S., Kopeykin P.M., Kudryavtsev I.V., Grudinina N.A., Andreeva E.A., Milman B.L., Orlov D.S.
Abstract
Cell-Penetrating Peptides (CPPs) are molecules that can easily internalize into eukaryotic cells, as well as deliver across their membranes a variety of compounds (proteins, nucleic acids, liposomes, nanoparticles, etc.). CPPs are considered as promising components of anticancer drugs, serving for delivery of active ingredients into malignant cells, therefore, a detailed study of a mechanism of action of CPPs and search for novel, more effective peptides are vital tasks of current biological and medical research. An ability of proline-rich peptides bactenecins (ChBac5, ChBac3.4, mini-ChBac7.5Na) and their truncated variants to penetrate into eukaryotic cells has been explored. By means of flow cytometry and confocal microscopy, we found that these peptides, tagged with a fluorescent dye BODIPY FL, rapidly penetrated into tumor cells and, to a lesser extent, into normal mammalian cells in vitro. The dependence of the internalization process on the medium temperature and energy metabolism of target cells was studied. The obtained data on the cell-penetratin activity of caprine bactenecins confirm the prospect of further investigations of these peptides as prototypes of new compounds - carriers of drugs into malignant or infected cells.
Medical academic journal. 2019;19(1S):178-179
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COMBINED ANTIBACTERIAL ACTION OF SALIVARY CATIONIC PROLINE-RICH PEPTIDES AND ANTIMICROBIAL PEPTIDES
Sukhareva M.S., Kopeykin P.M., Zharkova M.S., Shamova O.V.
Abstract
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.
Medical academic journal. 2019;19(1S):180-181
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EXPERIMENTAL SUBSTANTIATION OF THE IMMUNOSTIMULATING EFFECT OF BRANCHED-CHAIN AMINO ACIDS UNDER STRESS
Trushina E.N., Timonin A.N., Ryger N.A., Mustafina O.K., Kuznetsov V.D.
Abstract
The aim is to study the effect of branched-chain amino acid (BCAA) on cytokine synthesis in male Wistar rats on the background of cyclic starvation. A study of 2 months duration was performed on 60 rats, which were divided into 3 groups (20 rats in each group): rats of the control group (K-group) received standardized balanced laboratory feed for rodents ad libitum. The animals of the 1st experimental group (O-1 group) were fed according to the following scheme: the first day - feed ad libitum, the second and the third day - fasting, the rats of the 2nd experimental group (O-2 group) were given feed according to the same scheme, but with the addition of BCAA at a dosage of 70 mg/kg body weight per day. In the serum of rats, cytokine levels were determined: GM-CSF, INF-γ, IL-10, IL-12p70, IL-13, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL- 6, TNF-α on the Luminex 200 multiplex analyzer (Luminex Corporation, USA). Statistical processing of the results was performed using the IBM SPSS Statistics Version 20.0 application package (“IBM”, USA). As a result of the study, it was established that the consumption of BCAA by rats for 2 months on the background of cyclic starvation causes a decrease in the level of IL-10 and an increase in serum levels of IL-1a and IL-2 due to the activation of signaling pathways that regulate switching of the Th2 immune response to the predominant production of Th1 cytokines.
Medical academic journal. 2019;19(1S):182-184
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HUMAN BETA-DEFENSIN-3 GENE EXPRESSION IN THE NASAL AND SINONASAL MUCOSA
Tyrnova E.V.
Abstract
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.
Medical academic journal. 2019;19(1S):184-186
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THE INTERACTION OF ARENICIN-1 WITH C3B COMPLEMENT PROTEIN
Umnyakova E.S., Krenev I.A., Legkovoy S.V., Sokolov A.V., Rogacheva O.N., Ovchinnikova T.V., Kokryakov V.N., Berlov M.N.
Abstract
The complement system and antimicrobial peptides (AMPs) are known to be vital humoral factors of innate immunity. Earlier we showed the double-sided influence of arenicin-1 (Ar-1), the AMP from a sea polychaeta Arenicola marina, on the complement activation. In this work we studied the binding of Ar-1 to C3b protein, the fragment of the central complement component C3, using surface plasmon resonance. We also performed molecular docking and molecular dynamics of interaction between C3b fragment - C3c - and Ar-1. All these data showed that the influence of Ar-1 on complement activation might be realized through the interaction with C3b, the most important component for complement activation. Ar-1 may be used for the design of new complement regulators for treating complement-related diseases.
Medical academic journal. 2019;19(1S):187-188
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INFLUENCE OF SEMAX ON THE INTENSITY OF LIPID PEROXIDATION IN IMMUNOCOMPETENT ORGANS IN THE CONDITIONS OF “SOCIAL” STRESS
Samotrueva M.A., Yasenyavskaya A.L., Murtalieva V.K., Myasoedov N.F., Andreeva L.A.
Abstract
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.
Medical academic journal. 2019;19(1S):188-191
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INFLUENCE OF SEMAX ON THE LEVEL OF INTERLEUKIN-1βIN THE CONDITIONS OF “SOCIAL” STRESS
Yasenyavskaya A.L., Samotrueva M.A., Myasoedov N.F., Andreeva L.A.
Abstract
A study on the effect of Semax on the level of interleukin-1β under conditions of “social” stress was performed on non-white white rats-males. The formation of a stress reaction under the conditions of “social” exposure was confirmed by the presence of a “stress triad”, including adrenal hypertrophy, a decrease in the number of eosinophils in the peripheral blood and the presence of erosive and ulcerative lesions of the gastric mucosa. The level of serum IL-1β was determined by the method of enzyme-linked immunosorbent assay (ELISA). “Social” stress, formed as a result of inter-male confrontations, is accompanied by an increase in cytokine production, manifested by an increase in the concentration of interleukin-1β. Against the background of Semax administration to stressed animals, we can speak of this representative from the group of neuropeptides, as a possible means of correction, contributing to a decrease in the level of IL-1β.
Medical academic journal. 2019;19(1S):192-194
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COMBINED ACTION OF ANTIMICROBIAL PEPTIDES AND NONIONIC SURFACTANTS TOWARDS BACTERIA
Zharkova M.S., Orlov D.S., Kolobov A.A., Shamova O.V.
Abstract
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.
Medical academic journal. 2019;19(1S):194-196
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THE EFFECT OF VITAMIN D ON THE SEVERITY OF DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Aleksandrov V.A., Nikitina N.V., Shilova L.N., Aleksandrov N.I., Emelianov N.V., Aleksandrova E.E., Mozgovaya E.E., Zborovskaya I.A.
Abstract
Objective: to study the dependence of depressive disorders in patients with rheumatoid arthritis (RA) on vitamin D deficiency in blood serum. Material and methods. 88 women were examined (mean age - 54.2 ± 12.0 years, disease duration - 9.0 [3.5; 16.0] years) with a reliable diagnosis of RA. An enzyme immunoassay was used to determine the 25(OH)D in the serum of patients with RA. Depression was assessed using the Beck scale. Results. In 89.8% of patients, an insufficient level of 25(OH)D was detected in the serum. The presence of depression was observed in 66% of patients with RA. A negative correlation of average power (r = -0.38) was found between the the level of 25(OH)D and the severity of depression. A negative correlation of average power (r = -0.38) was found between the the level of 25(OH)D and the severity of depression. The relationship between 25(OH)D and ESR (r = 0.29), depression and intake (r = 0.22) and dose (r = 0.26) of corticosteroid hormones, the number of painful joints (r = 0.25) indicates on the involvement of these predictors and their mutual influence in metabolic and psychological processes in RA. Vitamin D is indirectly involved in inflammatory changes and central sensitization, which provokes psychological disorders in patients with RA. Conclusion. Correction of the deficiency of 25(OH)D can positively affect the reduction of the severity of depression and pain in RA.
Medical academic journal. 2019;19(1S):197-199
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CORRECTION OF STRESS-INDUCED HORMONAL CHANGES BY THE RIL-2 MEDICATION IN EXPERIMENTAL TRAUMATIC BRAIN INJURY
Fomicheva E.E., Shanin S.N., Filatenkova T.A., Serebryanaya N.B.
Abstract
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.
Medical academic journal. 2019;19(1S):199-200
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THE EFFECT OF АFOBAZOL ON THE NEUROAMINE STATUS OF THE THYMUS OF WHITE RATS
Gimaldinova N.E., Lyubovtseva L.A., Guryanova E.A., Vorobeva O.V.
Abstract
Often used in medical practice drug Afobazol has a wide range of actions. The paper describes the morphological changes of neuroamine-containing structures of the thymus of white rats with long-term (8 weeks) afobazole administration. By fluorescent histochemistry was determined by the content of catecholamines, histamine, and serotonin in the structures of the thymus. Under the influence of afobazole, the luminescent picture in the structures of the thymus changes, the clear boundary between the cortical and medullary substance of the thymus lobe is erased. The introduction of Afobazole leads to a decrease in the concentration of biogenic amines in premedullary GLA and an increase in the concentration in the microenvironment, which indicates a decrease in the amino-producing properties of these cells and the release of neurotransmitters from GLA.
Medical academic journal. 2019;19(1S):201-202
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SEMAPHORIN 3A - A NEW INTRATHYMIC SUPPRESSOR FACTOR
Rutto K.V., Kisseleva E.P.
Abstract
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.
Medical academic journal. 2019;19(1S):203-205
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PHARMACOLOGICAL CORRECTION BY PHENAZEPAM OF DISORDERS IN INTERACTION OF NERVOUS AND IMMUNE SYSTEMS DURING PREDATOR STRESS IN DANIO RERIO
Kosyakova G.P., Blazhenko A.A., Lebedev A.A.
Abstract
The behavior of Dario rerio fish under stress control (mental trauma modeling) and with the axiolytic drug phenazepam was studied. With the drug phenazepam - tranquilizer fish calm down and float to the top of the aquarium. Typically, this fish was used in research in the field of molecular genetics and developmental biology, but recently it has become attractive in the work on the creation of new drugs and the modeling of various physiological and pathological processes. Danio rerio is a model organism in developmental biology. Most human genes have homologs in zebra fish (70%-80%), and functional kinase domains have 100% identity. The hypothalamic-pituitary-adrenal axis corresponds to that in humans. The aim of our work is to determine the neuropeptides in the brain of Danio rerio after stress effects and the use of phenazepam.
Medical academic journal. 2019;19(1S):205-207
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ANTIAPOPTOSIS ACTIVITY OF PLANT POLYPRENYLPHOSPHATE AGAINST MACROPHAGE TARGET CELLS INFECTED WITH THE MURINE ENCEPHALOMYELITIS VIRUS
Kozhevnikova T.N., Sanin A.V., Ozherelkov S.V.
Abstract
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.
Medical academic journal. 2019;19(1S):207-209
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MODULATION OF B-LYMPHOCYTES ACTIVITY BY CHOLINOTROPIC DRUGS BEFORE WATER-IMMERSION STRESS
Nezhinskaya G.I., Krylova I.B.
Abstract
The aim of the work was to study the effect of modulation of B-lymphocytes activity with cholinotropic drugs on the stomach damage caused by water-immersion stress (WIS). The work was performed on male Wistar rats. Atropine (2 mg/kg), methacin (2 mg/kg) and choline alfoscerat (90 mg/kg) were administered 14 days before the WIS which lasted for 5 hours. The number of antibody-producing cells (APC) in spleen and the content of immunoglobulins IgA, IgG, IgM in blood were determined. The rats injected with saline were served as the control. On day 14 after administration of methacin or choline alfoscerat, but not atropine, an increase in the APC content in the spleen was observed comparing with control. At the same time, there was a significant decrease in the number of gastric ulcers. Thus on the model of water-immersion stress (WIS), it has been shown that B-lymphocytes can serve as a new target for the action of cholinotropic drugs, and modulation of their activity can provide effective prevention against stress.
Medical academic journal. 2019;19(1S):209-210
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EFFECTS OF KARMIZOLE DERIVATE ON THE EXPRESSION OF APO A-I GENE IN THE RAT’S HYPERLIPIDEMIA MODEL
Lizunov A.V., Okunevich I.V., Shabanov P.D.
Abstract
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.
Medical academic journal. 2019;19(1S):211-212
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THE EFFECTS OF ALLOFERON (ALLOKIN) IN THE THERAPY OF METABOLIC SYNDROME (A PILOT STUDY)
Didkovsky N.A., Malashenkova I.K., Abakumova J.V., Ogurtsov D.P., Krynskiy S.A., Hailov N.A., Chekulaeva E.I., Mamoshina M.V.
Abstract
The aim of this work was to study the influence of treatment with alloferon (allocin) in combination with pyrogenal and cytokine therapy on the parameters of immunity, systemic inflammation, levels of herpesvirus replication and biochemical profile of patients with metabolic syndrome to search for new approaches to the treatment of the early stages of the disease. Markers of systemic inflammation and immunity, including key cytokines and lymphocyte subpopulations, were investigated. It was found that 1 month after the start of the study in patients receiving only allokin, there were signs of activation of humoral immunity. In patients receiving complex therapy, there were signs of activation of the cell-mediated mechanisms of adaptive immunity. These changes persisted after 6 months and were not accompanied by signs of systemic inflammation when evaluated at 1 and 6 months. The results of further observation showed that in patients receiving complex therapy, there were positive changes in lipid profile, which were the most prominent at the end of the study. Thus, in this study it was shown that in patients with metabolic syndrome complex immunomodulatory therapy, including allokin, pirogenal, ingaron and Roncoleukin, led to the activation of the cellular link of adaptive immunity, without causing a long-term increase in the level of markers of systemic inflammatory response. During long term observation the patients had positive dynamics of the main markers of the lipid profile, and a reduce in the level of serum markers of systemic inflammation. These delayed effects can apparently be associated with immunomodulatory effects of therapy, including the possible activation of regulatory CD4+CD25+Foxp+ cells, which, according to the literature, have a protective effect in obesity, reducing insulin resistance.
Medical academic journal. 2019;19(1S):212-215
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TURMERIC EXTRACT IN CORRECTION OF NERVOUS AND IMMUNE SYSTEMS FUNCTIONAL ACTIVITY PARAMETERS IN EXPERIMENTAL ALCOHOLISM
Markova E.V., Goldina I.A., Goldin B.G., Knyazheva M.A., Savkin I.V.
Abstract
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.
Medical academic journal. 2019;19(1S):215-217
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CYTOKINE PROFILE OF RAT BLOOD SERUM DURING EXPERIMENTAL BRONCHOPULMONARY INFLAMMATION AND IMMUNOMODULATOR ADMINISTRATION
Mokrenko E.V., Shabanov P.D.
Abstract
Experimental bronchopneumonia was modeled by administering turpentine to the trachea under ether anesthesia. After the operation, the solution of one of the studied immunomodulators was intraperitoneally administered to the animals for 5 days (1 time/day): polyoxidonium - 0.75 mg/kg, trekrezan 25 mg/kg or metaprot 25 mg/kg. After decapitation, the interleukin profile was determined in the blood using commercial kits (Merk). Inflammation decreased blood concentrations of both proinflammatory factors (IL-1β, IL-2, IL-12, INF-γ and chemokine MCP-1), and anti-inflammatory (IL-4, IL-10) cytokines. At the same time, the levels of TNFα and IL-6, as well as the anti-inflammatory cytokine IL-13, increased. The introduction of immunomodulators, polyoxidonium, trekrezan or metaprot substantially normalized the level of pro- (IL-1β, IL-2, IL-12 (p7), chemokine MCP-1, INFα) and anti-inflammatory cytokines (IL-4, IL-10). The anti-inflammatory effect of drugs is associated with the normalization of cytokine metabolism.
Medical academic journal. 2019;19(1S):217-219
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EXPERIMENTAL MODELING OF MULTIPLE SCLEROSIS: THE RESULTS OF CORRECTIVE ACTION OF ACTIVE ANTIOXIDANT
Okunevich I.V.
Abstract
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.
Medical academic journal. 2019;19(1S):219-221
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CALPAIN ACTIVITY UNDER EXPERIMENTAL INCREASING OF DOPAMINE LEVEL
Pestereva N.S., Marshak A.Z., Karpenko M.N.
Abstract
The aim of our study was to identify the activity of calpains under conditions of an experimental increase in the level of dopamine. The work was performed at three levels: in vivo, in situ, in vitro. An in situ study was carried on a model of isolated nerve endings - synaptosomes. Using casein zymography in solution with FITC-casein, it was shown that incubation of synaptosomes dopamine leads to calpains secretion into the synaptosomal medium. The dopamine ability to directly activate calpain was demonstrated by casein zymography in a gel. Incubation in an activation buffer containing dopamine instead of the classical activator, calcium chloride, led to the activation of calpain-2. An in vivo experiment was performed on Wistar rats. The experimental group was orally administered the drug L-dopa (100 mg/kg), the control group - saline was injected in the same way.
Medical academic journal. 2019;19(1S):221-222
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MODERN BIOLOGICALLY ACTIVE SUBSTANCES STIMULATING SOMATIC CELLS AND FUNCTIONS OF NERVOUS AND IMMUNE SYSTEMS
Samuylenko A.Y., Grin S.A., Shabunin S.V., Raevsky A.A., Miller R.N., Melnik N.V., Pavlenko I.V., Albulov A.A.
Abstract
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.
Medical academic journal. 2019;19(1S):223-225
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DESIGN OF COMPOUNDS WITH ANTICONVULSANT ACTIVITY AMONG NMDA-RECEPTOR LIGANDS
Brusina M.A., Kubarskaya L.G., Iljin V.V., Nikolaev D.N., Piotrovskiy L.B.
Abstract
NMDA receptors play an important role in the development of immune responses. Therefore, the design of NMDAergic compounds presents great interest in various areas, including immunology. We have previously shown that some imidazole-4,5-dicarboxylic acid (IDA) derivatives are ligands of these receptors, and can exhibit both agonistic and antagonistic activities. In continuation of these studies and in attempt to establish the main structural parameters that determine the type of the activity, we developed a general method for synthesis of 1-, 2-mono and 1,2-disubstituted IDA derivatives. To establish the structure-activity relationship in the series under investigation, which include about 30 compounds, we try to find correlations of biological activity with the structure of compounds and some their physicochemical parameters (for example, partition coefficients between the lipophilic and hydrophilic phases). Pharmacological analysis in vivo of this set in various models under ip administration showed that a part of them induces a pre-convulsive state in mice of the CBA line, while the other part has a pronounced anticonvulsant effect on the NMDA-induced seizures. Thus, in the series of compounds under investigation substances that are both convulsants and anticonvulsants were found. The results of this study will allow us to design new drugs with anticonvulsant action.
Medical academic journal. 2019;19(1S):225-226
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BLOOD RAT CYTOKINES IN EXPERIMENTAL PROSTATITIS AND AFTER THE ACTION OF IMMUNOMODULATORS
Mokrenko E.V., Shabanov P.D.
Abstract
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.
Medical academic journal. 2019;19(1S):226-227
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EFFECT OF rTMS ON BLOOD CONTENT OF DEHYDROEPIANDROSTERONE-SULFATE (DEAS) AND CORTISOL IN MEN AND WOMEN WITH PARKINSON’S DISEASE (PD): A PILOT PLACEBO-CONTOLLED STUDY
Zhanaeva S.Y., Gevorgyan M.M., Dzemidovich S.S., Kulikova K.I., Idova G.V., Danilenko K.V., Aftanas L.I.
Abstract
PD is a neurodegenerative disease characterized with loss of dopamine neurons and associated with neuroinflamation and unbalanced in HPA-axis. We investigated the content of cortisol and DEAS - hormones of HPA-axis in patients with PD after applying rTMS. Feng S.F. et al. (2012) showed that rTMS improves the balance of HPA axis hormones during depression, which is one of the non-motor manifestations of PD. PD patients were randomized into groups with active rTMS (13 men, 11 women) and sham rTMS (10 men, 15 women).The 10Hz rTMS was performed sequentially over 2 targets: the primary motor cortex and the DLPFC daily for 20 days. Outcome measures included the indicators of MDS-UPDRS (Part 3) scale, content of cоrtisol and DEAS in the peripheral blood.The Motor Examination Part scores demonstrated clinically meaningful improvement only in the active treatment group (p < 0.01). The content of the DEAS in this group was negatively correlated with indicators of scales of clinical manifestations, stress and anxiety (p < 0.05). In this group an increase of content of DEAS in the peripheral blood of men was found (p < 0.01, Wald-Wolfowitz Runs Test). Thus, the rTMS increases the levels of a wellknown neuroprotective hormone and a modulator of DA activity DEAS only in men.
Medical academic journal. 2019;19(1S):227-228
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Effect of xenon on pain severity and adaptational status of neuro-oncological and oncogynecological patients
Popova N.N., Zinkovich M.S., Shikhlyarova A.I., Zhukova G.V., Rozenko L.Y., Protasova T.P., Goncharova A.S., Bragina M.I.
Abstract
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.
Medical academic journal. 2019;19(1S):228-230
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Neurotrophic factors and inflammatory cytokines in the mother-placenta-fetus system in experimental hyperhomocysteinemia
Milyutina Y.P., Shcherbitskaia A.D., Zalozniaia I.V., Kerkeshko G.O., Arutjunyan A.V.
Abstract
An essential aspect of metabolic imbalance of L-homocysteine and its accumulation in blood (hyperhomocysteinemia) is its aggravating effect in pregnancy. However, little is known about the effects of maternal increased L-homocysteine levels on brain development of fetuses. In the development of the fetus, accompanied by changes in metabolism in the placenta, an important role belongs to neurotrophic factors and apoptosis. This study investigated the effects of chronic L-methionine administration on some parameters of inflammation and on neurotrophic factor levels in the brain of embryos, as well as in the placenta and serum of pregnant rats. The observed disturbances can be resulted from both a direct impact of L-homocysteine and its metabolites on the fetal CNS, and hyperhomocysteinemia-caused changes in normal state of the placenta.
Medical academic journal. 2019;19(1S):230-231
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The effect of orexin A application on the reaction of microglia cells body size stimulated by LPS injection
Synchikova A.P., Horiuchi H., Nabekura J.
Abstract
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.
Medical academic journal. 2019;19(1S):232-233
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THE DEVELOPMENT OF NEUROINFLAMMATORY PROCESSES IN RATS IN EARLY POSTNATAL ONTOGENESIS AFTER PRENATAL HYPERHOMOCYSTEINEMIA
Shcherbitskaia A.D., Vasilev D.S., Tumanova N.L., Milyutina J.P., Zalozniaia I.V., Arutjunyan A.V.
Abstract
Prenatal exposure to high levels of homocysteine has long-term impact on growth retardation of nervous system development and is related to central nervous system diseases in children. However, it is not well-characterized whether gestational exposure to hyperhomocysteinemia (HHC) affects the development of nervous system in offspring. It was observed disturbed neuroblast generation and migration, neuronal death in cortex, revealed as reduction of pyramidal neurons number, and activation of glia in the month after birth in offspring subjected to HHC. These disorders may be associated with changes in the content of pro-inflammatory cytokines in the cortex tissue of HHC pups.
Medical academic journal. 2019;19(1S):234-235
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The effect of various models of cold stress on cytokine production by the cells of the mouse peritoneal cavity under conditions of blockade of opiate receptors
Sharav’eva I.L., Gein S.V.
Abstract
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.
Medical academic journal. 2019;19(1S):236-236
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The Impact and the Prevention of Burnout on Psychic activity and Nervous and Immune Systems
Radtchenko-Draillard S.
Abstract
The aim of my study is to analyze the causes and consequences of burnout on the dysfunction of psychic activity and weakening of the nervous and immune systems in their interaction. By presenting different research studies and my own analytical and practical results, this article traces the various orientations and identifies the symptoms, ranging from the quasi-normal state to the serious pathology in individuals suffering from burnout. The burnout methods and the psychotherapeutic techniques presented, which can generate the burnout cases, present a common backbone to the different approaches exposed in order to try to explain what this concept covers and the way it manifests itself.
Medical academic journal. 2019;19(1S):236-239
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