LIPID PROFILE OF BLOOD SERUM, LIPID PEROXIDATION AND NITROXiDERGIC SYSTEM OF VETERANS OF THE AFGHAN CONFLICT WITH EARLY FORMS OF CHRONIC BRAIN ISCHEMIA

A determination of lipid profile, indices of lipid peroxidation and ergic system in veterans and civilians with early forms of chronic brain ischemia. The data confirming the presence of oxidative stress at cellular membranes showed high antioxidant activity and ergic systems are more pronounced in veterans with DEP-I, which may reflect the growth of nerve tissue hypoxia in the progression of chronic cerebrovascular insufficiency in the background of post-stress disorder

GROWTH OF BIOLOGICAL MARKERS OF AGING AND ALLOSTASIS IN VETERANS OF THE AFGHAN WAR CONFLICT WITH EARLY FORMS OF CHRONIC BRAIN ISCHEMIA

We investigated the rate of biological aging, the levels of stress hormones and regulatory cytokines in Afghan war veterans and civilians with early forms of chronic brain ischemia. The study established acceleration of aging according to biological age indicators, earlier clinical onset of early forms of chronic cerebrovascular diseases associated with the processes of posttraumatic disregulation of cerebral and systemic vascular tone, the accumulation of "allostatic load” in the form of hypercortisolemia, growth regulator and angiogenic cytokines in veterans of the Afghan conflict

Fortification of food with micronutrients: development of methodological and regulatory framework in the Russian Federation

The available scientific literature, domestic and international regulatory codes of normative documents concerning the fortification of various types of food products have been analyzed. The groups of food products of conventional and regular consumption included into the diets of all categories of consumers, recommended for fortification with essential micronutrients, have been determined: wheat and cereal flour (spelt wheat, buckwheat, oat, corn flour, etc.); pastry; milk and dairy products, including ice cream; non-alcoholic soft drinks; mineralized drinking water; fruit and vegetable juices; fat and oil products (vegetable oils, margarines, spreads, mayonnaise); confectionery and sweets (pastry, sugar, chocolate); cereals (breakfast cereals, muesli, ready-to-eat extruded cereals, instant pasta and cereals, mixtures for bakery, flour for sweet pastry); food concentrates (jelly, instant drinks, concentrates of sweet foods, instant food, instant cereal concentrates); table salt. The groups of food products assigned for certain categories of population are used as part of therapeutic diets for patients with various diseases (metabolic disorder syndrome, cardio-vascular system pathology with atherosclerotic vascular injury, type 2 diabetes mellitus, gastrointestinal tract diseases, non-alcoholic fatty liver disease, diabetic nephropathy, etc.), as well as assigned to reduce the risk of diseases developing, the nutrients are recommended for targeted fortification of certain types of food. Examples of micronutrients fortification of sausages and minced meat semifinished products are given below. Requirements for fortification of mass consumption food products and for fortification of foods for special dietary uses are formulated in this article, the amount of fortifying components in the various groups of food products are justified, ensuring their efficiency for improving the micronutrient status and safety of its consumption. Based on the analysis of the available scientific literature, domestic and international regulatory framework of normative documents on fortification of various types of food products, recommendations have been developed for fortification of food with micronutrients

Tuning strategy for Curie-temperature enhancement in the van der Waals magnet Mn_1+xSb_2−xTe₄

The van-der-Waals antiferromagnetic topological insulator MnBi2Te4 is one of the few materials that realize the sought-after quantum anomalous Hall (QAH) state and quantized surface charge transport. To assess the relevance of its isostructural analog MnSb2Te4 as a potential QAH candidate, the roles of Mn/Sb site mixing and cationic vacancies need to be clarified. Recent findings have shown that non-stoichiometry in Mn1±xSb2∓xTe4 is an efficient tuning knob to achieve a net spin-polarized state and to raise the magnetic ordering temperature well above that of MnBi2Te4. Here, we report the crystal structure, the bulk and the surface magnetism of two new Mn1+xSb2−xTe4 samples: Mn1.08Sb1.92Te4(x ≈ 0.1) with TC = 44 K, and Mn2.01Sb1.19Te4(x ≈ 1.0) with the record TC = 58 K. We quantify the site mixing comprehensively by combining various structural probes on powders and single crystals, and then employ bulk, local (electron spin resonance), and spectroscopic (x-ray magnetic circular dichroism) probes to connect these insights to the magnetism of these materials. We demonstrate that Mn over-stoichiometry up to x = 1.0, in combination with a particular Mn/Sb intermixing pattern and the increasingly three-dimensional character of the magnetic order, push the TC upwards. The tendency towards more robust ferromagnetism mediated by stronger interlayer exchange in Mn1+xSb2−xTe4 upon increasing x is confirmed by bulk magnetometry and by a series of density-functional-theory calculations of model structures with varying intermixing.</p

Production operation of small petroleum enterprises in Tomsk region

Implementing resource-innovative strategy to develop Russian fuel-and-energy sector implies the promotion of small oil production enterprises developing fields with the reserves of less than 5 mln. tons. However, the efficiency of such enterprises, investigated on the example of Tomsk region (considering the indexes of oil extraction, growth of reserves, amount of capital expenditures and geological surveys), signifies the presence of definite tendencies. Consequently, management decisions concerning economic, organizational, financial and fiscal character should be taken in order to eliminate detrimental factors

Two novel mutations associated with ataxia-telangiectasia identified using an ion ampliSeq inherited disease panel

© 2017 Kuznetsova, Trofimov, Shubina, Kochetkova, Karetnikova, Barkov, Bakharev, Gusev and Sukhikh. Ataxia-telangiectasia (A-T), or Louis-Bar syndrome, is a rare neurodegenerative disorder associated with immunodeficiency. For families with at least one affected child, timely A-T genotyping during any subsequent pregnancy allows the parents to make an informed decision about whether to continue to term when the fetus is affected. Mutations in the ATM gene, which is 150 kb long, give rise to A-T; more than 600 pathogenic variants in ATM have been characterized since 1990 and new mutations continue to be discovered annually. Therefore, limiting genetic screening to previously known SNPs by PCR or hybridization with microarrays may not identify the specific pathog enic genotype in ATM for a given A-T family. However, recent developments in next-generation sequencing technology offer prompt high-throughput full-length sequencing of genomic fragments of interest. This allows the identification of the whole spectrum of mutations in a gene, including any novel ones. We report two A-T families with affected children and current pregnancies. Both families are consanguineous and originate from Caucasian regions of Russia and Azerbaijan. Before our study, no ATM mutations had been identified in the older children of these families. We used ion semiconductor sequencing and an Ion AmpliSeq ™ Inherited Disease Panel to perform complete ATM gene sequencing in a single member of each family. Then we compared the experimentally determined genotype with the affected/normal phenotype distribution in the whole family to provide unambiguous evidence of pathogenic mutations responsible for A-T. A single novel SNP was allocated to each family. In the first case, we found a mononucleotide deletion, and in the second, a mononucleotide insertion. Both mutations lead to truncation of the ATM protein product. Identification of the pathogenic mutation in each family was performed in a timely fashion, allowing the fetuses to be tested and diagnosed. The parents chose to continue with both pregnancies as both fetuses had a healthy genotype and thus were not at risk of A-T

Исследование содержания метаболитов оксида азота, α1-кислого гликопротеииа и его гликоформ в конденсатах выдыхаемого воздуха больных бронхиальной астмой

The aim of this study was to evaluate nitric oxide (NO) and α1-acid glycoprotein (AGP) with its glycoforms as biochemical markers of inflammatory activity in the airways of bronchial asthma (BA) patients. We examined expired breath condensate (EBC ) samples of 132 patients with severe (32) and moderate (30) BA and 30 healthy non-smoking volunteers using spectrophotometry to study NO metabolites and immunoassay to study AGP. The EBC NO metabolites levels were found to increase significantly in BA exacerbation depending on its severity. In stable BA patients the NO metabolites levels decreased but they were higher in severe and moderate BA than in healthy volunteers. The highest AGP concentration was measured in BA exacerbation with the maximal values in severe disease. In stable BA the AGP level decreased in all BA groups but it remained higher than in healthy volunteers. The qualitative structure of AGP changed during the BA exacerbation, especially in severe cases. So, according to our results the NO metabolites, AGP and its glycoforms reflect the airway inflammatory activity and can be applied to control the disease.С целью оценки возможности использования метаболитов оксида азота (N0), белка острой фазы α-кислого гликопротеина (АКГ) и его гликоформ в качестве биохимических маркеров для определения активности воспаления при бронхиальной астме (БА) были обследованы конденсаты выдыхаемого воздуха (КВВ) 132 больных с разной степенью тяжести заболевания в стадии обострения и ремиссии при использовании различных лечебных программ. Наши исследования показали, что уровень метаболитов N0 в КВВ больных БА значительно возрастает в период обострения параллельно тяжести приступа. В ремиссию БА содержание метаболитов N0 в КВВ снижается, но остается повышенным при тяжелом и среднетяжелом течении астмы с наиболее высокой концентрацией при отсутствии регулярного применения базисной противовоспалительной терапии. Содержание АКГ в КВВ повышается при обострении БА, снижается в период ремиссии, но остается выше, чем у здоровых, при тяжелом и среднетяжелом течении астмы. Установлено, что при обострении БА меняется качественный состав АКГ с повышением содержания всех его гликоформ. Таким образом, определение метаболитов N0, АКГ и его гликоформ в КВВ пациентов с БА является чувствительным методом диагностики степени тяжести и фазы заболевания, широкое внедрение которого в клиническую практику позволит максимально оптимизировать программы лечения

Состояние адипокиновой регуляции и эндотелиальной дисфункции у пациентов с хронической обструктивной болезнью легких c различной минеральной плотностью костной ткани

The objective of this study was to investigate serum levels of leptin, adiponectin and endothelin1 and to search their role in development of osteoporosis in chronic obstructive pulmonary disease (COPD) patients.Methods. Lung function, body mass index (BMI), bone mineral density (BMD)of the lumbar spine and the femoral neck, and serum concentrations of leptin, adiponectin and endothelin1 were measured in 126 patients with COPD diagnosed according to GOLD and in 86 healthy subjects.Results. Among COPD patients, 43% had osteoporosis, 34% had osteopenia and 23% had normal BMD. Osteopenia was diagnosed in 35% of controls. The mean BMD value in stage 2 COPD patients corresponded to osteope nia; in stage 3 and IV COPD patients corresponded to osteoporosis. Generally, BMD correlated with FEV1 (r = 0.38, p &lt; 0.05 for the lumbar spine; r = 0.43, p &lt; 0.05 for the femoral neck) and with pCO2 (r = –0.46, p &lt; 0.05 and r = –0.39, p &lt; 0.05, respectively) in COPD patients. No significant difference was found for leptin and adiponectin concentrations between stages 1 and 2 COPD patients and controls. Leptin level decreased and adiponectin level increased in stages 3 and 4 COPD patients compared to controls (p &lt; 0.05). There was a direct relationship between BMI and leptin (r = 0.64; p &lt; 0.001) and an inverse relationship between BMI and adiponectin (r = –0.51; p &lt; 0.01). FEV1 and DLCO were related to leptin only (p &lt; 0.001). Leptin was directly related to the femoral neck and the lumbar spine BMDs (r = 0.66, p &lt; 0.001 and r = 0.49, p &lt; 0.05, respectively), while adiponectin was inversely related to BMD (r = –0.43, p &lt;0.05 for the femoral neck; r = –0.49, p &lt;0.001 for the lumbar spine). We found inverse relationships between endothelin1 and the lumbar spine BMD (r = –0.51, p &lt;0.01), leptin (r = –0.46, p &lt; 0.05), FEV1 (r = –0.43, p &lt; 0.05) and PO2 (r = –0.54, p &lt; 0.05) and direct relationships between endothelin1 and pCO2 (r = 0.68, p &lt; 0.001) and adiponectin (r = 0.51, p &lt; 0.05). A relationship between endothelin1 and adipokines was found only in osteoporotic COPD patients.Conclusion. Our results suggest that serum adipokines and endothelin1 are involved in the pathogenesis of respiratory failure and bone density loss in COPD patients. The most pronounced changes in concentration of these biomarkers and close relationships between them and BMD were observed in patients with osteoporosis.Целью исследования явилось изучение содержания лептина, адипонектина и эндотелина1 (ЭТ1) в сыворотке крови и определение их роли в формировании остеопороза (ОП) при хронической обструктивной болезни легких (ХОБЛ).Материалы и методы. Легочная функция, индекс массы тела (ИМТ), минеральная плотность костной ткани (МПКТ) в поясничном отделе позвоночника и шейке бедра, уровни лептина, адипонектина и ЭТ1 определялись у пациентов с ХОБЛ (n = 126) в зависимости от стадии по GOLD (Global Initiative for Chronic Obstructive Lung Disease – Глобальная стратегия диагностики, лечения и профилактики ХОБЛ) и здоровых (n = 86).Результаты и обсуждение. ОП при ХОБЛ установлен у 43 % обследуемых, остеопения – у 34 %, у 23 % больных показатели были в норме. Остеопенический синдром выявлен у 35 % лиц группы контроля. Средние значения МПКТ в позвоночнике и шейке бедра в общей группе ХОБЛ при II стадии (GOLD) соответствовали остеопении, при ХОБЛ III и IV стадии (GOLD) – ОП. Обнаружена зависимость между МПКТ и объемом форсированного выдоха за 1ю секунду (ОФВ1) (позвоночник: r = 0,38; p &lt; 0,05; шейка бедра: r = 0,43; p &lt; 0,05) и рСО2 (позвоночник: r = –0,46; p &lt; 0,05; шейка бедра: r = –0,39; p &lt; 0,05) в общей группе ХОБЛ. Содержание лептина и адипонектина при ХОБЛ I и II стадии (GOLD) не отличалось от контроля. При ХОБЛ III и IV стадии (GOLD) уровень лептина снижался, а адипонектина – повышался по отношению к контролю (p &lt; 0,05). Выявлены прямая связь между ИМТ и уровнем лептина (r = 0,64; p &lt; 0,001) и отрицательная корреляция с уровнем адипонектина (r = –0,51; p &lt; 0,01). Связь между показателями ОФВ1 и диффузионной способности легких определены только с лептином (p &lt; 0,001). Показатель уровня лептина прямо коррелирует с МПКТ в шейке бедра и позвоночнике (r = 0,66; p &lt; 0,001; r = 0,49; p &lt; 0,05 соответственно), тогда как уровень адипонектина имеет негативную связь (шейка бедра: r = –0,43; p &lt; 0,05; позвоночник: r = –0,49; p &lt; 0,001). Установлена обратная корреляционная связь между содержанием ЭТ1 и МПКТ в позвоночнике (r = –0,51; p &lt; 0,01) и лептином (r = –0,46; p &lt; 0,05) с ОФВ1 (r = –0,43, p &lt; 0,05) и pО2 (r = –0,54, p &lt; 0,05), прямая зависимость – с pСО2 (r = 0,68; p &lt; 0,001) и адипонектином (r = 0,51; p &lt; 0,05). Взаимосвязи ЭТ1 с адипокинами установлены только у больных ХОБЛ с ОП.Заключение. Результаты исследования свидетельствуют об участии адипокинов и ЭТ1 в патогенезе дыхательной недостаточности и потере плотности кости при ХОБЛ. Наиболее выраженный характер изменений и тесные корреляционные связи данных показателей с МПКТ отмечены у пациентов с ОП

A Case of Medullary Carcinoma of the Jejunum Combined with the Intestinal Lymphangiectasia Accompanied by the Malabsorption Syndrome

Aim: to present a clinical and morphological observation of an extremely rare combination of medullary carcinoma of the jejunum and intestinal lymphangiectasia in a 33-year-old patient with clinical features of malabsorption syndrome over the 10 years.Key points. An autopsy revealed a tumor formation spreading from the wall of the jejunum to the mesentery, with metastases to the mesenteric lymph nodes. The medullary carcinoma with positive expression of СD117, DOG1, EMA, PanCK, PDL-1, vimentin, mosaic non-intense expression of CA19-9, calretinin, CD10, CDX2, CEA, MUC-5AC, SATB2, and negative reaction to ALK, CD3, CD8, CD20, CD30, CD31, CD34, CD45, CD56, chromogranin, CK7, CK20, desmin. The proliferative index was high: Ki-67 &gt; 80 %. Moreover, during the histological examination of the intestinal wall, intestinal lymphangiectasia complicated by the malabsorption syndrome was revealed.Conclusion. The uniqueness of this clinical and morphological case is in the combination of medullary carcinoma of the jejunum metastasized to the mesenteric lymph nodes with the underlying intestinal lymphangiectasia accompanied by the development of malabsorption syndrome

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model

INTRODUCTION: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. METHODS: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. RESULTS: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on adhesive substrates (type I collagen, fibronectin and laminin) and induced different responses in small GTPases, such as RhoA and Rac-1 activation, and changes in cell morphology. In addition, binding to various ECM components caused redistribution of chemokine receptors at tumour cell surfaces. In vivo, blocking CXCR4 decreased extravasation of highly metastatic MDA-MB-231 cells (p < 0.05), but initial cell adhesion within the liver sinusoids was not affected. In contrast, the less metastatic MDA-MB-468 cells showed reduced cell adhesion but similar migration within the hepatic microcirculation. CONCLUSION: Chemokine-induced extravasation of breast cancer cells along specific ECM components appears to be an important regulator but not a rate-limiting factor of their metastatic organ colonization.Claudia Wendel, André Hemping-Bovenkerk, Julia Krasnyanska, Sören Torge Mees, Marina Kochetkova, Sandra Stoeppeler and Jörg Haie