EMBRIOGENESIS OF NEURONAL ELENENTS (GLIOBLASTS AND GABAA RECEPTORS) IN THE HUMAN BRAIN NEUROIMMUNE SYSTEM UNDER PRENATAL ALCOHOL EXPOSURE

Exposure to alcohol causes imbalances in neuroimmune function and impaired brain development. Alcohol activates the innate immune signaling pathways in the brain. Neuroimmune molecules expressed and secreted by glial cells of the brain (microglia, oligodendroglia) alter the function of neurons and further stimulate the development of alcoholic behavior. Various signaling pathways and brain cells are involved in the transmission of neuroimmune signals. Glial cells are the main sources of immune mediators in the brain, which respond to and release immune signals in the central nervous system. The aim of this study was to study neuronal elements: morphometric parameters of glioblasts, synaptic structures and properties of synaptosomal GABAA-benzodiazepine receptors of the neuroimmune system in the embryogenesis of the human brain under perinatal exposure to alcohol. Changes in glioblasts in the brain tissue of human embryos and fetuses were revealed under conditions of chronic prenatal alcoholization with an increase in gestational age compared with control subgroups: a significant increase in the average number of glioblasts, the length of the perimeters of presynaptic terminal structures, postsynaptic density, presynaptic terminal regions were significantly less (p < 0.01) in the study group than in the control comparison group. Exposure to ethanol leads to a decrease in the affinity of GABAA-benzodiazepine receptors, which affects neuronal plasticity associated with the development and differentiation of progenitor cells (glioblasts and neuroblasts) during embryogenesis of the human brain and leads to suppression of GABAergic function in the brain. This causes a disruption in the interconnection of embryonic cells in the brain, leads to excessive apoptosis due to the activation of glial cells of the nervous tissue, disruption of neuroimmune function in the developing brain, changes in neuronal circuits, as well as a change in the balance of excitatory and inhibitory effects, which affects the functional activity in the central nervous system. Glial activation is a compensatory reaction caused by neuroplastic changes aimed at adapting the developing brain of the embryo and fetus under conditions of neurotoxicity and hypoxia under the influence of prenatal alcoholization of the maternal organism and the effect of ethanol on the fetus. The dynamics of changes in glial elements and receptor activity in the nervous tissue of human embryos and fetuses under conditions of prenatal exposure to alcohol indicates a more pronounced effect of alcohol on the earliest stages of human embryo development, which is of great practical importance in planning pregnancy and the inadmissibility of alcoholization of the mother in order to avoid negative consequences in offspring

Detection of specific antibodies to Schmallenberg virus using microneutralisation test

The article presents data on microneutralization test for detection of specific antibodies to Schmallenberg virus. The method is characterized by high sensitivity and specificity. It can be used for analysis of blood sera of different species of animals

The significance of soluble molecules of cellular adhesion, nitric oxide metabolites, and endothelin-1 and their associations as markers of progression of inflammation in COPD

© 2017, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the investigation was to assess the significance of the content of metabolites of the nitric oxide, sICAM-1 and sICAM-3 in blood serum and in exhaled breath condensate, the serum level of endothelin-1 as systemic and topical markers of inflammation in patients with COPD, and their correlations with the parameters of lung ventilation function. Materials and methods. 91 patients with COPD, aged from 46 to 67, and 21 healthy, non-smoking volunteers took part in the study. The material for investigation was blood serum and exhaled breath condensate. Results. The severity of progression of COPD was linked with an increase in the serum content of sCD50, sCD54, ET-1, as well as in the concentrations of metabolites of nitric oxide in blood and in exhaled breath condensate. For the patients with COPD we determined the associations between the function of pulmonary ventilation and the levels of ET-1, sICAM-1, sICAM-3 and the value of ΣNO – 2 /NO – 3 . The resulting correlations between the concentration of soluble adhesion molecules, the values of nitrosative stress, and ET-1 level indicate that they are involved in the genesis of chronic inflammation in COPD patients

Optimization of medium composition and study of growth stages of <i>Mycoplasma bovis</i> “Kaluga 2020” isolate

Mycoplasma bovis is considered one of bovine mycoplasmosis pathogens responsible for respiratory diseases, mastitis, arthritis and keratoconjunctivitis. The paper presents results of the study on optimizing the component composition of the culture medium for Mycoplasma bovis “Kaluga 2020” isolate, as well as the study of this pathogen’s growth stages. The color-changing units assay and the culture method combined with colony-forming unit quantification were used for determination of Mycoplasma activity. It was found that when cultured in an optimized nutrient medium based on modified Hayflick broth, the microorganism enters a logarithmic growth phase after first 24 hours ofgrowth, in 72 hours the Mycoplasma culture enters astability phase, and adecline phase is recorded in 84 hours. The effect of percentage content of glucose, fresh yeast extract and horse serum in the nutrient medium on accumulation of Mycoplasma bovis “Kaluga2020” isolate was evaluated using the one-factor-at-a-time approach. It was found that the greatest effect on Mycoplasma accumulation was exerted by such growth factors as fresh yeast extract and horse serum in the nutrient medium (p &lt; 0.05), while changes in the amount of glucose did not stimulate Mycoplasma bovis growth. Based on results of the conducted studies, the appropriate composition was determined and the optimal content of growth factors in the medium for culturing Mycoplasma bovis “Kaluga 2020” isolate was selected: 12.5%of fresh yeast extract and 25% of horse serum. The use of the optimized nutrient medium based on modified Hayflick broth allowed 5-fold increase in accumulation of Mycoplasma biomass (3.98 × 109CFU/ml)compared to the standard medium (0.79 × 109CFU/ml)

Портрет пациента с системной красной волчанкой для назначения ингибитора интерферона типа I анифролумаба

In recent years the use of monoclonal antibodies that block activity of type I interferon (IFN) or its receptors has become the new approach in the pharmacotherapy of systemic lupus erythematosus (SLE).Objective: to characterize patients with SLE treated with the type I IFN receptor inhibitor anifrolumab (AFM, Saphnelo®).Material and methods. The prospective 12-month study included 21 patients with SLE who met the 2012 SLICC criteria. Standard laboratory and immunological markers for SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE and the CLASI index was used to determine the severity of the mucocutaneous syndrome. Organ damage was assessed using the SLICC/ACR Damage Index (DI). The LupusQol and FACIT-Fatigue questionnaires were used to analyze health-related quality of life (HRQoL).Results and discussion. Female patients prevailed in the study, female/male ratio – 17 (81%)/4 (19%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. The majority of patients (86%) had moderate or high disease activity according to the SLEDAI-2K index. Among the clinical manifestations of SLE, skin and mucous membranes lesions predominated (81%). Non-erosive polyarthritis of varying severity was observed in 66% of cases. Serositis showed 24% of patients (pleurisy, pericarditis), 43% had hematological abnormalities (hemolytic anemia, leukopenia, lymphopenia) and 14% - urinary syndrome (daily proteinuria up to 0.5 g/l and/or urinary sediment – leukocytes/erythrocytes/cylinders up to 5 in the field of view in the absence of urinary tract infection). All patients had immunological disorders. 14% of them were diagnosed with antiphospholipid syndrome (APS) and 43% with Sjögren's syndrome.All patients received hydroxychloroquine, 95% received glucocorticoids (GC) from 5 to 60 mg/day, 66% received immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate). 33% of patients had anamnesis of treatment with biologic disease modifying antirheumatic drugs (rituximab, belimumab, dual anti-B-cell therapy) and Janus kinase inhibitor baricitinib. All patients experienced a significant deterioration in HRQoL.Conclusion. The indications for prescribing AFM to 21 patients with SLE were: active SLE according to SLEDAI-2K and/or CLASI with predominant involvement of skin, its appendages and development of polyarthritis with immunological disorders, intolerance/ineffectiveness of previous standard therapy and inability to achieve low average daily doses of oral GCs. Other clinical manifestations in some patients were: serositis, mild hematological disorders (Coombs-positive anemia, leukopenia), urinary syndrome. AFM could be prescribed for a combination of SLE with secondary APS and Sjögren's syndrome as well as for a high DI SLICC.В последние годы новым подходом к фармакотерапии системной красной волчанки (СКВ) стало применение моноклональных антител, блокирующих активность интерферона (ИФН) типа I или его рецепторов.Цель исследования – охарактеризовать пациентов с СКВ, получавших ингибитор рецепторов ИФН типа I анифролумаб (АФМ, Сафнело®).Материал и методы. В проспективное 12-месячное исследование включен 21 пациент с СКВ, соответствовавший критериям SLICC 2012 г. У всех пациентов исследовали стандартные лабораторные и иммунологические маркеры СКВ. Для определения активности СКВ использовался индекс SLEDAI-2К, степени выраженности кожно-слизистого синдрома – индекс CLASI. Оценку повреждения органов проводили с помощью индекса повреждения (ИП) SLICC/ACR. Для изучения качества жизни, связанного со здоровьем (КЖСЗ), применяли опросники LupusQol и FACIT-Fatigue.Результаты и обсуждение. В исследовании преобладали женщины, соотношение женщины/мужчины – 17 (81%)/4 (19%), медиана возраста – 31 [27; 46] год, длительности заболевания – 9 [6,0; 11,0] лет. У большинства пациентов (86%) отмечалась средняя или высокая степень активности заболевания по индексу SLEDAI-2К. Среди клинических проявлений СКВ преобладали изменения кожи и слизистых оболочек (у 81%). Неэрозивный полиартрит различной степени выраженности наблюдался в 66% случаев. Серозит (плеврит, перикардит) выявлен у 24% пациентов, гематологические нарушения (гемолитическая анемия, лейкопения, лимфопения) – у 43%, мочевой синдром (суточная протеинурия до 0,5 г/л и/или мочевой осадок – лейкоциты/эритроциты/цилиндры до 5 в поле зрения при отсутствии мочевой инфекции) – у 14%. Все пациенты имели иммунологические нарушения. У 14% из них диагностирован антифосфолипидный синдром (АФС), у 43% – синдром Шегрена.Все пациенты получали гидроксихлорохин, 95% – глюкортикоиды (ГК) от 5 до 60 мг/сут, 66% – иммуносупрессанты (циклофосфан, мофетила микофенолат, азатиоприн, метотрексат). Терапия генно-инженерными билогическими препаратами (ритуксимаб, белимумаб, двойная анти-В-клеточная терапия) и ингбитором Янус-киназ барицитинибом в анамнезе проводилась в 33% случаев. У всех пациентов отмечалось значительное ухудшение КЖСЗ.Заключение. Показаниями для назначения АФМ 21 пациенту с СКВ были: активная по SLEDAI-2K и/или CLASI СКВ с преимущественным поражением кожи, ее придатков и развитием полиартрита с иммунологическими нарушениями, непереносимость/неэффективность предшествующей стандартной терапии, а также невозможность достижения низких среднесуточных доз пероральных ГК. Дополнительными клиническими проявлениями у части пациентов являлись: серозит, нетяжелые гематологические нарушения (Кумбс-позитивная анемия, лейкопения), мочевой синдром. Допускалось назначение АФМ при сочетании СКВ с вторичным АФС и синдромом Шегрена, а также при высоком ИП SLICC

REPARATIVE PROPERTIES OF LINSEED OIL AT ALCOHOLIC GASTRITIS

This article evaluated the reparative properties of linseed oil in acute alcoholic gastritis

ИССЛЕДОВАНИЕ ОСТЕОПЛАСТИЧЕСКИХ СВОЙСТВ РЕЗОРБИРУЕМОГО ПОЛИ-3-ГИДРОКСИБУТИРАТА IN VIVO НА МОДЕЛЯХ СЕГМЕНТАРНОЙ ОСТЕОТОМИИ

A family of materials  based  on biodegradable polymer-3-hydroxybutyric acid (polyhydroxybutyrate, PHB) has been  developed for the purposes of reparative osteogenesis. Osteoplastic properties of bulk implants  PHB and PHB composition with hydroxyapatite (HA) have been  investigated in comparison with branded drugs Bio-Oss ® in vivo via the model of segmental osteotomy. It is indicated that  reconstructive bone  formation is more  active when implants  with PHB as a main component are used.Для целей  репаративного остеогенеза разработано семейство материалов на основе биоразрушаемого полимера-3-гидроксимасляной кислоты (полигидроксибутирата, ПГБ). Остеопластические свойства  объемных имплантатов из ПГБ и композиции ПГБ с гидроксилапатитом (ГАП) исследованы in vivo на модели сегментарной остеотомии в сравнении с фирменным препаратом Bio-Oss®.  Показано, что реконструктивный остеогенез происходит более активно  при использовании имплантатов, содержащих в качестве основного компонента ПГБ.

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event

Sediment respiration pulses in intermittent rivers and ephemeral streams

Intermittent rivers and ephemeral streams (IRES) may represent over half the global stream network, but their contribution to respiration and carbon dioxide (CO2) emissions is largely undetermined. In particular, little is known about the variability and drivers of respiration in IRES sediments upon rewetting, which could result in large pulses of CO2. We present a global study examining sediments from 200 dry IRES reaches spanning multiple biomes. Results from standardized assays show that mean respiration increased 32–66‐fold upon sediment rewetting. Structural equation modelling indicates that this response was driven by sediment texture and organic matter quantity and quality, which, in turn, were influenced by climate, land use and riparian plant cover. Our estimates suggest that respiration pulses resulting from rewetting of IRES sediments could contribute significantly to annual CO2 emissions from the global stream network, with a single respiration pulse potentially increasing emission by 0.2–0.7%. As the spatial and temporal extent of IRES increases globally, our results highlight the importance of recognizing the influence of wetting‐drying cycles on respiration and CO2 emissions in stream networks

A global analysis of terrestrial plant litter dynamics in non-perennial waterways

Perennial rivers and streams make a disproportionate contribution to global carbon (C) cycling. However, the contribution of intermittent rivers and ephemeral streams (IRES), which sometimes cease to flow and can dry completely, is largely ignored although they represent over half the global river network. Substantial amounts of terrestrial plant litter (TPL) accumulate in dry riverbeds and, upon rewetting, this material can undergo rapid microbial processing. We present the results of a global research collaboration that collected and analysed TPL from 212 dry riverbeds across major environmental gradients and climate zones. We assessed litter decomposability by quantifying the litter carbon-to-nitrogen ratio and oxygen (O2) consumption in standardized assays and estimated the potential short-term CO2 emissions during rewetting events. Aridity, cover of riparian vegetation, channel width and dry-phase duration explained most variability in the quantity and decomposability of plant litter in IRES. Our estimates indicate that a single pulse of CO2 emission upon litter rewetting contributes up to 10% of the daily CO2 emission from perennial rivers and stream, particularly in temperate climates. This indicates that the contributions of IRES should be included in global C-cycling assessments