Pathways of neuro-immune communication: past and present time, clinical application

Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain

Using an OPEN UMS format for document flow formalization in medicine

The question about construction of medical documents by means of AURRORA MIS with the use of the Open UMS format is considered in the work. The approach suggested allows data storage in the electronic form suitable for generation of required statistical reports and different researches and preserves a possibility of correct data interpretation

X-ray diffraction study and luminescence of agates of Southern Siberia

Central part of Kuznetsk Basin is known in the narrow circle of researchers as one of the regions of Siberia where agate mineralization is widespread. In spite of rather wide distribution of these quartz-chalcedony aggregates, still there are some unresolved issues about their origin. In this context it may be informative to use such methods as luminescence analysis and estimation of crystallinity indexes of minerals which constitute agates. Layer-by-layer X-ray diffraction study of minerals which make up distinct layers of agates and onyxes allowed identifying three minerals alternating: chalcedony, quartz and (less frequently) cristobalite. Calculation of crystallinity indexes of all of the layers with use of X-ray diffraction analysis helped to find changes of proportion between two states of silica – high-molecular (polymerized) and monomeric. X-ray luminescence analysis results confirmed this finding. Authors suppose that monomeric state is particularly related to high value of crystallinity index and presence of defects which are responsible for short-wavelength luminescence (280 nm)

Social theater as a form of crime prevention in the adolescent environment

В статье рассматриваются возможности использования технологий социального театра в качестве формы профилактики правонарушений подростков в образовательной среде колледжа.The article discusses the possibilities of using social theater technologies as a form of prevention of juvenile delinquency in the educational environment of the college

RESPONSE OF LYMPHOID CELLS TO REGULATORY SIGNAL OF INTERLEUKIN 1 AS AN INDEX OF LYMPHOCYTE ACTIVITY

Intensivity of lymphocyte proliferative activity is an important and almost the only indicator of the level of functional activity of these cells, and the immune system in general. The aim of this study was to develop an adequate physiological test to determine the degree of functional activity of lymphoid cells. The choice of IL-1 as an activator of proliferation is justified by the presence of receptors to IL-1 on lymphoid cell membranes, the key role of this cytokine in the initiation of a wide range of biological effects of the immune system to antigen, including participation in intercellular cooperation and distant action on various cells. It was found that the ligand-receptor interaction of IL-1 by type I receptor activates neutral sphingomyelinase, and the sphingomyelin pathway of signal transduction in lymphocytes. The degree of activation of this enzyme depends on the type of stress and correlates with changes of the vector of humoral immune response and proliferative activity of lymphocytes. The level of IL-1 increases, but the activity of neutral sphingomyelinase and lymphoid cell proliferation is significantly reduced after applications of immunosuppressive stress in mice and rats. The change of the degree of lymphocyte proliferation has become a marker of the severity of the pathological process in clinic. A high degree of correlation between the low intensity of peripheral blood lymphocyte proliferation in response to IL-1 action and the unfavorable disease outcome in patients with severe combined trauma and children with purulent meningitis was established. Thus, the degree of lymphocyte proliferation in response to the action of the regulatory signal of IL-1 can be used both for the analysis of the effectiveness of immunomodulators, and as diagnostic and prognostic indicator in clinical practice

FOXP3, IL2R, CD8A and RORγ gene expression in peripheral blood leukocytes of healthy people and patients with arterial hypertension

Impaired balance of T regulatory and T effector lymphocytes has recently been considered as an important pathogenetic link in arterial hypertension (AH). There are, however, contradictory literature data about contents of these cells in the patients with hypertension, or obtained in experimental animal models of induced hypertension. Most results about changed patterns of immune cells in cardiovascular diseases were obtained by means of flow cytometry. There are also some works on expression of genes encoding surface and cytoplasmic differentiation antigens of immune cells in the patients with cardiovascular pathologies. These results coincide with the data obtained with flow cytometric techniques. Purpose of the present study was to analyze of the levels of gene transcripts encoding differentiation markers of regulatory (FOXP3, IL2R) T cells, effector T subpopulations (T helpers 17 (RORγ), and CD8 lymphocytes (CD8A) in healthy subjects and the patients with arterial hypertension (stages I-II). We examined healthy individuals (40 people, 20 men and 20 women), 27 patients with hypertension who did not receive antihypertensive therapy (14 men and 13 women), 26 hypertensive patients taking β-adrenergic receptor blockers (metoprolol or bisoprolol), including 12 men and 14 women. The relative levels of transcripts in peripheral blood leukocytes were assessed by real-time RT-PCR. It was shown that the transcriptional activity of FOXP3, IL2R, RORγ, and CD8A genes in peripheral blood leukocytes of the diseased people was significantly higher than in healthy individuals (p < 0.01). This finding may indicate an increased number of circulating T regulatory lymphocytes, CD8+ cells and T helpers 17 in hypertensive patients, and activation of T cell immunity in these patients. There were no statistically significant gender differences in FOXP3, IL2R, RORγ and CD8A gene expression in leukocytes, both in the group of healthy people and in hypertensive patients. The patients receiving cardioselective β-adrenergic receptor blockers (metoprolol and bisoprolol) exhibited lower expression of these genes, thus, probably, indicating antiinflammatory and immunomodulatory properties of these drugs

Correlation between morphological characteristics of colon cancer and amount of eosinophilic granulocyte in peripheral blood as prognostic marker

The aim of the investigation was to investigate correlation between .morphological characteristics of colon cancer (CC) and amount of eosynophils in peripheral blood (EoPB) before and after radical operation. 197 cases were analyzed. Statistical analysis revealed negative correlation between EoPB and tumor size, it's degree of differention, the depth of invasion and lymph nodes involvement, but the regularity was observed only in patients before radical operation; distant metastasis formation in postoperative period was associated with the lower amount of EoPB as compare with patients with dissemination. The results of the investigation allow to suspect the better prognosis for CC patients with the higher level of EoPB.Целью исследования стало изучение зависимости морфологических параметров рака толстой кишки (РТК) и количества зозинофилов в периферической крови (ЭоПК) до и поле проведения радикальной операции. Были проанализированы 197 случаев. Статистический анализ выявил отрицательную обратную связь между количеством ЭоПК и размером опухоли, степенью ее дифференцировки, степенью поражения лимфатических узлов и степенью инвазии, причем данные закономерности наблюдались только у пациентов до проведения радикальной операции; появление отдаленных гематогенных метастазов в послеоперационном периоде было связано с более низким количеством ЭоПК, чем в случаях без диссеминирования опухоли. Результаты исследования позволяют судить о более благоприятном прогнозе у пациентов с РТК при более высоком уровне ЭоПК

Immunological predictors of type 1 diabetes mellitus (literature review)

Background: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency due β-cell destruction and following hyperglycaemia. Specific markers of T1DM are pancreatic islet-targeting autoantibodies that are found months to years before symptom onset, and can be used to identify individuals who are at risk of developing T1DM.Aim: The study is aimed at the review of current knowledge of diabetes-related autoantibodies as biomarkers of T1DM.Materials and methods: Foreign and national clinical studies on this topic were included. PubMed, Medline and ­eLibrary were searched.Results: Modern ideas about known diabetes-specific autoantibodies as markers of autoimmune inflammation of β-cells of the pancreas were discussed. The analysis of their independent diagnostic value in predicting the occurrence of T1DM were carried out.Conclusion: There is no unified concept in the literature on this issue. Current data on autoantibodies in T1DM show a ­significant individual variability in the timing, dynamic changes and autoantibody composition in T1DM progression

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury