Cytokine profile and expression of FYN, ZAP-70 and LAT during concanavalin a stimulation in patients with resistant bronchial asthma

Background: Bronchial asthma (BA) is one of the most spreading chronic lung pathology in the world. The disease is characterized by high heterogeneity of clinical phenotypes including resistant forms which provoke significant clinical problem. Immune shift from Th2 to alternative immunological response is considered to be a mechanism of drug-resistance in BA treatment but this issue is not considerably studied yet. Aims: Detection of distinctive patterns in cytokine secretion and genetic expression (ZAP-70, FYN and LAT) of naïve and concanavalin A stimulated lymphocytes in patients with resistant BA. Materials and methods: The study enrolled ten patients in each group: subjects with treatment resistant BA, severe BA, and controls (30 in total). During the experiment, all patients with BA received treatment according to the condition. For each participant lymphocytes isolation from venous blood was performed. Cells were cultured with concanavalin A and without stimulation. Concentrations of cytokines IL-2, IL-12, TNF-α, IL-4, IL-5, and IL-6 in supernatants were measured with ELISA. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of LAT, ZAP-70, and FYN genes. Results: Significant disease contribution to the lymphocyte secretion profile was established without concanavalin A stimulation: increased levels of IL-2 and IL-4 was observed in lymphocytes of patients with resistant BA if compared to the results of gorup with severe BA. Patients with resistant BA were characterized by weak cytokine response to the stimulation: only TNF-α and IL-5 levels were significantly increased whereas in group with severe BA all cytokines concentrations increased except IL-12, in controls - except IL-12 and IL-2. Significant FYN upregulation was identified in resistant BA group if compared with other groups, and in severe BA patients if compared with controls. The concanavalin A-stimulated cells showed increased expression of ZAP-70 in cells of patients with resistant BA compared to control group. Conclusions: Lymphocytes from patients with resistant BA are characterized by lack of cytokine response to concanavalin A stimulation, alteration of cytokine secretion, and genetic expression profile similar to cells with low sensitivity to apoptosis. The FYN gene is a perspective target for finding approaches to overcome resistance to steroid drugs in bronchial asthma. © 2018 Izdatel'stvo Meditsina. All rights reserved

Correlation between emotional-affective disorders and gut microbiota composition in patients with Parkinson's disease

Background: Despite the efforts of scientific community the data available on the correlation between emotional-affective symptoms of Parkinson's disease and changes in microbiome is still scarce. Deeper studies of nonmotor symptoms evident in premotor stages of the disease and the reciprocal influence of microbiota may help to understand the etiology and pathogenesis of PD neurodegeneration better. The aim of the study was to discover the relations between emotional-affective disorders prevalent in PD population and changes in gut microbiota composition. Methods:51 patient diagnosed with PD participated in the study. Every participant's emotional-affective state was examined using Beck's Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Taxonomic richness of microbiome was studied using 16S ribosomal RNA gene sequencing, bioinformatics, and statistical analysis. Results: Anxiety and depression are prevalent affective disorders in patients with PD. In our study, most of the subjects demonstrated certain anxiety and depression. Taxonomic diversity of gut microbiota in BP was increasing with the increase in anxiety levels, reaching the maximum in the group with subclinical anxiety, and decreasing in the group with clinically significant anxiety disorder. At the species level, patients with clinically significant anxiety had higher abundance of Clostridium clariflavum compared to the anxiety-free patients. Patients with moderate depression were characterized by the higher prevalence of Christensenella minuta, Clostridium disporicum, and Oscillibacter valericigenes compared to subjects without depression or with mild depression. Conclusion: The data we received in our study allow better understanding of PD pathogenesis

Диагностический потенциал кишечной микробиоты при болезни Паркинсона

Background. Nowadays many efforts are taken in searching for Parkinson’s disease biomarkers, especially for an early recognition of the disease. The gut microbiota is one of the potential sources of biomarkers, changes in the composition of which in PD are actively studied.The aim of this study is to identify microbiota biomarkers in the Parkinson’s disease with an estimated accuracy of the diagnostics, including differential diagnostics, relative to other neurological diseases for patients of the Russian population.Material and methods. One hundred ninety-two metagenomics profiles from patients with Parkinson’s disease (n = 93), people with other neurological diagnoses (n = 33), and healthy controls (n = 66) were included in this study. These profiles were obtained with amplicon sequencing of bacterial 16S rRNA genes. Classifying models were made using the naive Bayes classifier, the artificial neural network, support vector machine, generalized linear model, and partial least squares regression.As a result we established that an optimal classification by the composition of the gut microbiota on the validation sample (sensitivity 91.30%, specificity 91.67% at 91.49% accuracy) amid patients was demonstrated with a naive Bayes classifier using the representation of the following genera as predictors: Christensenella, Methanobrevibacter, Leuconostoc, Enterococcus, Catabacter, Desulfovibrio, Sphingomonas, Yokenella, Atopobium, Fusicatenibacter, Cloacibacillus, Bulleidia, Acetanaerobacterium, and Staphylococcus.Conclusions. Information of the gut microbiota taxonomic composition may be used in differential diagnosis of Parkinson’s disease. Введение. В настоящий момент ведется активная работа по поиску биомаркеров болезни Паркинсона(БП), в частности для проведения ранней диагностики данного заболевания. Одним из потенциальных источников биомаркеров является кишечная микробиота, изменения в составе которой при БПактивно изучаются.Целью данной работы является идентификация микробиотных биомаркеров БП с оцененной точностью диагностики, в том числе и дифференциальной, относительно других неврологических заболеваний для пациентов российской популяции.Материалы и методы. В исследование было включено 192 метагеномных профиля кишечноймикробиоты, полученных в результате ампликонного секвенирования бактериальной 16S рРНК отпациентов с болезнью Паркинсона (n = 93), лиц контрольной группы (n = 66) и другими неврологи-ческими заболеваниями (n = 33). Для создания классифицирующих моделей использовали наивныйбайесовский классификатор, искусственную нейронную сеть, машину опорных векторов, обобщенную линейную модель и регрессию методом частичных наименьших квадратов.Результаты. Оптимальные показатели классификации пациентов по составу кишечной микробиотына валидационной выборке (чувствительность 91,30%, специфичность 91,67% при точности в91,49%) продемонстрировал наивный байесовский алгоритм при использовании представленностимикроорганизмов родов Christensenella, Methanobrevibacter, Leuconostoc, Enterococcus, Catabacter,Desulfovibrio, Sphingomonas, Yokenella, Atopobium, Fusicatenibacter, Cloacibacillus, Bulleidia, Acetanaerobacterium и Staphylococcus в качестве предикторов.Выводы. Информация о таксономическом составе кишечной микробиоты может быть использованадля проведения дифференциальной диагностики болезни Паркинсона

Связана ли микрофлора кишечника с болезнью Паркинсона?

Parkinson’s disease (PD) is a neurodegenerative disorder with a complex pathogenesis. Today more and more studies are focusing on microbiota-gut-brain axis searching the causes of neurodegenerative and neuroinflammatory processes.The aim of our study is to determine the relationship between the composition of gut microbiota and clinical manifestations of PD.Materials and methods. We examined 89 patients with a PD diagnosis. Clinical assessment was performed including medical history collection, rating disease stage using Hoehn and Yahr scale. Motor and nonmotor symptoms as well as possible complication were examined using the Unified Parkinson’s Disease Rating Scale. In addition, patients were asked to fill in Parkinson’s Well-Being Map and defecation diary that included Bristol scale. DNA isolation was performed in accordance with the method described. Preparation of libraries and amplicon sequencing of marker variable region V3–V4 of bacterial 16S rRNA genes was performed with MiSeq device (Illumina, USA) according to manufacturer’s standard protocol. Filtering readings by quality and their taxonomic classification were carried out using QIIME version 1.9.0 software. The assessment of statistical differences in abundance of taxonomic units among the groups of patients was performed using IBM SPSS Statistics 23.1 software.As a result, we have identified significant differences in the abundance of seven genera among the groups of patients with different forms of the disease. We identified about 40 genera constituting 54.8% of the intestinal microbiota, that had a correlation with the clinical manifestations of the disease. These microorganisms might be involved in the pathogenesis of PD and, thus, require more clinical research in the light of emerging new methods of altering microbiotic composition by correcting dysbiosis to improve disease management and outcome. Болезнь Паркинсона (БП) – это нейродегенеративное заболевание со сложным патогенезом. В поисках причин развития нейродегенеративного и нейровоспалительного процесса все большую роль отводят оси «микробиота – кишечник – мозг».Цель исследования – выявление связи между составом микробиоты кишечника и клиническими проявлениями БП.Материал и методы. Было обследовано 89 пациентов с диагнозом БП. Был учтен анамнез, тяжесть болезни по шкале Хен и Яра, произведена оценка степени проявлений БП с помощью Унифицированной шкалы оценки проявлений БП. Дополнительно пациентами были заполнены карты оценки самочувствия пациента с болезнью Паркинсона (Parkinson’s Well-Being Map). Для оценки консистенции каловых масс использовалась Бристольская шкала. Выделение ДНК проводилось в соответствии с ранее описанной методикой. Подготовка библиотек и ампликонное секвенирование маркерного вариабельного участка V3–V4 бактериальных генов 16S рРНК проводились на приборе MiSeq (Illumina, США) согласно стандартному протоколу производителя. Фильтрация прочтений по баллам качества и их таксономическая классификация проведены с помощью программного обеспечения QIIME версии 1.9.0. Осуществлена оценка α- и β-разнообразия, проанализированы различия в представленности отдельных таксономических единиц между группами пациентов при использовании программного обеспечения IBM SPSS Statistics 23.1.Результаты. Выявлены значимые различия в представленности семи родов между группами пациентов с разными формами заболевания. Всего было идентифицировано около 40 родов, относительная представленность которых в сумме составила 54,8% от общего микробиотического состава кишечника, причем часть родов имели корреляции с клиническими проявлениями заболевания.Заключение. Вероятно, эти микроорганизмы могут являться непосредственными участниками патогенеза БП и требуют более пристального внимания в свете новых тенденций воздействия на организм путем коррекции микробиотического состава кишечника

Сравнительный анализ кишечной микробиоты при болезни Паркинсона и других неврологических заболеваниях

Currently the role of microbiota in diseases pathogenesis, its therapeutic and diagnostic potential are of the utmost interest for scientists and medical doctors. Parkinson’s disease is neurodegenerative disorder for which microbiota’s dysbiosis was previously shown.The main goal of the study is to compare the colon microbiota composition in case of Parkinson’s disease and other neurological pathologies, including idiopathic familial dystonia, essential tremor, multiple sclerosis, multiple system atrophy in order to determine the intestinal flora landscape specific to Parkinson’s disease.Material and methods. One hundred twenty-six patients, 93 with Parkinson’s disease and 33 with other neurological pathology were examined. For all patients, physical examination and fecal samples collection were performed. Microbiota taxonomic composition was analyzed by sequencing of bacterial 16S rRNA genes followed by bioinformatic and statistical analysis.As a result of the study, significant differences between groups in microbiota composition were found. Gut microbiota of patients with Parkinson’s disease was characterized by increase of Desulfovibrio piger, Lactobacillus mucosae, Yokenella regensburgei, Alistipes indistinctus, Oscillospira capillosus, Clostridium bolteae, Soleaferrea massiliensis, Butyricimonas virosa, Dorea massiliensis, Victivallis vadensis abundances. Patients with other neurological diseases had increased levels of bacteria belonging to Blautia, Intestinibacter, Coprococcus genera and Anoxystipes fissicatena, Fusobacterium periodonticum, Gemmiger formicilis, Papillibacter cinnamivorans, Roseburia faecis, Lachnoclostridium indolis, Clostridium populeti, Clostridium tertium, Roseburia intestinalis, Eubacterium desmolans, Eubacterium cylindroides, Clostridium clariflavum, Eubacterium eligens, Coprococcus eutactus, Intestinibacter bartlettii species in their gut microbiota.Consequently, gut microbiota in case of Parkinson’s disease was different from the microbiota of patients with other neurological diseases, including neuroinflammatory and neurodegenerative disorders, in terms of taxonomic diversity and composition. В настоящее время большой интерес представляет роль микробиоты в патогенезе различных болезней, а также ее диагностический и терапевтический потенциал. Болезнь Паркинсона – нейродегенеративное заболевание, для которого было показано изменение состава кишечной микробиоты в сравнении со здоровым контролем.Цель данного исследования – сравнительная характеристика кишечной микробиоты лиц с болезнью Паркинсона и другими неврологическими заболеваниями, включая идиопатическую семейную дистонию, эссенциальный тремор, рассеянный склероз, множественную системную атрофию для определения микробиотического ландшафта, характерного именно для болезни Паркинсона.Материал и методы. В исследование были включены 93 пациента с диагнозом болезни Паркинсона и 33 пациента с иными неврологическими заболеваниями. Для каждого пациента проведено физикальное обследование и собраны образцы фекалий. Определение состава микробиоты проводилась секвенированием бактериальных генов 16S рРНК с последующим биоинформатическим и статистическим анализом.Результаты. При сравнительном анализе состава микробиоты были найдены значимые различия. Микробиота кишечника лиц с болезнью Паркинсона характеризовалась увеличением содержания бактерий видов Desulfovibrio piger, Lactobacillus mucosae, Yokenella regensburgei, Alistipes indistinctus, Oscillospira capillosus, Clostridium bolteae, Soleaferrea massiliensis, Butyricimonas virosa, Dorea massiliensis, Victivallis vadensis. У лиц с другими неврологическими заболеваниями преобладали бактерии родов Blautia, Intestinibacter, Coprococcus и видов Anoxystipes fissicatena, Fusobacterium periodonticum, Gemmiger formicilis, Papillibacter cinnamivorans, Roseburia faecis, Lachnoclostridium indolis, Clostridium populeti, Clostridium tertium, Roseburia intestinalis, Eubacterium desmolans, Eubacterium cylindroides, Clostridium clariflavum, Eubacterium eligens, Coprococcus eutactus, Intestinibacter bartlettii.Выводы. Микробиота кишечника при болезни Паркинсона отличается по таксономическому разнообразию и бактериальному составу от микробиоты пациентов с другими неврологическими заболеваниями, в том числе нейровоспалительными и нейродегенеративными.

E-LEARNING STRATEGY AT TECHNICAL UNIVERSITY

The paper explores emerging trends of modern society that have created tremendous impacts on higher education, both in worldwide and national scales. Implementing e-learning initiatives as the response of higher education institutions to major challenges isdiscussed. Educational process reforming through the use and development of e-learning technologies at the National Research Tomsk Polytechnic University is shown

GELASTIC SEIZURES IN TUBEROUS SCLEROSIS

The authors consider the historical description, nosological entity, clinical and electroencephalographic manifestations of gelastic seizures, a rare type of epileptic seizures manifesting as sudden attacks of spasmodic laughter. They describe their case of gelastic seizures in a child with tuberous sclerosis

The first results of tuberous sclerosis registry

The purpose of establishing and maintaining a tuberous sclerosis registry is to collect data on the clinical manifestations and outcomes of the disease, and drug and non-drug interventions. The registry includes data on 303 people (156 men and 147 women) aged 4 months to 28 years who are diagnosed as having this disease. Most patients are the residents of Moscow and its Region (102/303; 33,6%). Thirty (9,9%) of the 303 patients are registered to have a family history of tuberous sclerosis. TSC1 and TSC2 gene mutations are detected in 29 (38,6%) and 46 (61,4%) patients, respectively. The TSC2 gene mutations previously undescribed in the world literature are found in 10 patients. There is epilepsy in 86,8% (263/303), intellectual developmental disorders in 39,3% (119/303), subependymal giant cell astrocytomas in 16,2% (49/303), tubers in 61% (81/131), subependymal nodules in 65,7% (86/131), hypopigmentation spots in 66,3% (201/303), facial angtofibromas in 29,4% (89/303), cardiac rhabdomyomas in 44,2% (134/303), and renal angiomyolipomas in 41,6% (126/303). West's syndrome is noted in 68 (25,9%) of the 262 epileptic patients; symptomatic focal epilepsy is seen in 149 (56,9%) patients. Seven patients took everolimus for subependymal giant cell astrocytomas. The registry demonstrates the late diagnosis of tuberous sclerosis, the limitation of genetic testing, and physicians' inadequate attention to the psychiatric manifestations of the disease