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

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

Comparative efficacy of Exenatide and Metformin in patients with type 2 diabetes mellitus with obesity

The purpose of the study is to compare the effects of drugs from the group of glucagon–like peptide agonists - 1 – Exenatide and biguanides — Metformin in patients with diabetes mellitus and obesity, the effect on body mass index (BMI), waist size (OT) and the course of gastroesophageal reflux disease (GERD).Цель исследования – сравнить эффекты лекарственных средств из группы агонистов глюкагоноподобного пептида - 1 – Эксенатид и бигуанидов - Метформин у пациентов с сахарным диабетом и ожирением, влияние на индекс массы тела (ИМТ), объем талии (ОТ) и течение гастроэзофагальной рефлюксной болезни (ГЭРБ)

Эффективность и безопасность длительного применения низкомолекулярных гепаринов у пациентов с системной красной волчанкой и антифосфолипидным синдромом

   To date, the management of patients with antiphospholipid syndrome (APS) with ineffectiveness and/or intolerance to vitamin K antagonists and direct oral anticoagulants remains controversial. One of the treatment strategies is the administration of low molecular weight heparins (LMWH) over a long period of time.   Objective: to evaluate the efefficacy and safety of long-term treatment with LMWH in patients with APS.   Material and methods. The study included 15 patients (13 women and 2 men) with APS. In 2 of them APS was isolated, in 12 it was combined with systemic lupus erythematosus (SLE), and in 1 – with SLE and psoriatic arthritis. The mean age of patients was 44 ± 12 years, and the mean duration of disease was 12 [6; 18] years. All patients were repeatedly examined in the V. A. Nasonova Research Institute of Rheumatology during hospitalizations and continued outpatient care in the clinical diagnostic center of the Institute.   Results and discussion. Ten (67 %) patients received nadroparin, 5 (33 %) patients received enoxaparin. The median duration of therapy was 4 [1; 10] years. Indications for the use of LMWH were inefficacy and intolerance of oral anticoagulants (n = 12, 100 %) and vascular involvement such as thromboangiitis obliterans with the development of chronic arterial insufficiency, ulcers and necrosis of the toes (n = 6, 40 %). During therapy, 13 (86 %) of 15 patients showed clinical improvement: healing of ulcers and necrosis, reduction in the stage of arterial insufficiency, recanalization of venous blood clots. During the entire treatment period with LMWH, one patient experienced a relapse of thrombosis due to an insufficient dose of the drug. No hemorrhagic complications occurred in any case. Other adverse events, including elevated liver aminotransferases, osteoporosis, and thrombocytopenia, were also not observed.   Conclusion. The results obtained suggest that long-term therapy with LMWH may be safe and effective in patients with APS.   До настоящего времени тактика ведения больных антифосфолипидным синдромом (АФС) с неэффективностью и/или непереносимостью антагонистов витамина К и прямых оральных антикоагулянтов остается спорной. Одной из стратегий терапии стало назначение низкомолекулярных гепаринов (НМГ) на длительный период.   Цель – оценить эффективность и безопасность длительного лечения НМГ у пациентов с АФС.   Материал и методы. В исследование включено 15 больных (13 женщин и 2 мужчины) с АФС. У 2 из них АФС был изолированным, у 12 сочетался с системной красной волчанкой (СКВ) и у 1 – с СКВ и псориатическим артритом. Средний возраст больных составил 44 ± 12 лет, медиана длительности заболевания – 12 [6; 18] лет. Все пациенты неоднократно находились на стационарном лечении в ФГБНУ «Научно-исследовательский институт ревматологии им. В. А. Насоновой»» и продолжали амбулаторное наблюдение в клинико-диагностическом центре института.   Результаты и обсуждение. Надропарин получали 10 (67 %) больных, эноксапарин – 5 (33 %). Медиана длительности терапии составила 4 [1; 10] года. Показаниями для назначения НМГ были неэффективность и непереносимость пероральных антикоагулянтов (n = 12, 100 %) и поражение сосудов по типу облитерирующего тромбангиита с развитием хронической артериальной недостаточности, язв и некрозов пальцев стоп (n = 6, 40 %). На фоне терапии у 13 (86 %) из 15 пациентов отмечалось клиническое улучшение: заживление язв и некрозов, уменьшение стадии артериальной недостаточности, реканализация тромбов венозного русла. За весь период лечения НМГ рецидив тромбоза возник у 1 больной на фоне недостаточной дозы препарата. Ни в одном случае не было геморрагических осложнений. Другие нежелательные явления, в том числе повышение уровня печеночных аминотрансфераз, остеопороз и тромбоцитопения, также не зафиксированы.   Заключение. Полученные результаты позволяют считать, что долгосрочная терапия НМГ у больных АФС может быть безопасной и эффективной

Application of 57Fe Mössbauer spectroscopy as a tool for mining exploration of bornite (Cu5FeS4) copper ore

Nuclear resonance methods, including Mössbauer spectroscopy, are considered as unique techniques suitable for remote on-line mineralogical analysis. The employment of these methods provides potentially significant commercial benefits for mining industry. As applied to copper sulfide ores, Mössbauer spectroscopy method is suitable for the analysis noted. Bornite (formally Cu5FeS4) is a significant part of copper ore and identification of its properties is important for economic exploitation of commercial copper ore deposits. A series of natural bornite samples was studied by 57Fe Mössbauer spectroscopy. Two aspects were considered: reexamination of 57Fe Mössbauer properties of natural bornite samples and their stability irrespective of origin and potential use of miniaturized Mössbauer spectrometers MIMOS II for in-situ bornite identification. The results obtained show a number of potential benefits of introducing the available portative Mössbauer equipment into the mining industry for express mineralogical analysis. In addition, results of some preliminary 63,65Cu nuclear quadrupole resonance (NQR) studies of bornite are reported and their merits with Mössbauer techniques for bornite detection discussed

REPARATIVE PROPERTIES OF LINSEED OIL AT ALCOHOLIC GASTRITIS

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