The surface electrical heterogeneity of the membranes with the different degree of cation-exchanger dispersity

The work is supported by the grant of the President of the Russian Federation MK-925.2018.3. The authors are grateful to the «MEGA» a.s. company (Czech Republic) and its owner Mr. L. Novak for providing experimental samples of the Ralex CM Pes sulfocation-exchange membranes. Microphotographs of the membranes surface were obtained at the CCUSE of VSU

Micro-relief and roughness of the surface of the profiled sulfocation-exchange membrane after its contact with phenylalanine solution

The work was conducted under financial support of RFBR (project N 18-08-01260)

Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt

AFM-analysis of the surface of a profiled sulfocation-exchange membrane after dialysis of phenylalanine solutions

Методом атомно-силовой микроскопии исследована поверхность профилированной катионообменной мембраны МК-40пр до и после диализа растворов аминокислоты. Определены микропрофили и среднестатистические параметры шероховатости поверхности исходной кондиционированной мембраны и образца после контакта с раствором фенилаланина.The profiled cation-exchange membrane MK-40pr surface is explored by methods of a atomic-force microscopy before and after dialysis the amino acid solution. The microprofiles and the аverage statistical parameters of roughness of a surface of initial conditioned membrane and sample after contact with phenylalanine are obtained.АСМ-изображения получены в ЦКПНО ВГУ. Работа выполнена при финансовой поддержке РНФ (проект № 17-19-01486)

ИСТОРИЯ ОТДЕЛА ВИРУСОЛОГИИ И МОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИХ МЕТОДОВ ИССЛЕДОВАНИЯ ДЕТСКОГО НАУЧНО-КЛИНИЧЕСКОГО ЦЕНТРА ИНФЕКЦИОННЫХ БОЛЕЗНЕЙ

The article deals with the history of formation of virology laboratory since 1963 after the resolution of the Academy of Medical Sciences of the USSR and the Ministry of Public Health on the expansion of virology investigation in the USSR.The results of the research work on studying various infections in children, developing new modified approaches to etiological express-diagnostics of the diseases, including those introduced into practice of the laboratory and regional medical centers are generalized. The laboratory got the name of the Department of Etiological Diagnostics Methods due to the basic direction of the research work. The primary goal of the department is to develop the methods and diagnostic algorithms for definite verification of infectious forms and the prognosis of the development of pathological process that allows determining the direction of further therapeutic approach to improve the disease outcome. In 2008 the Department of Etiological Diagnostics Methods began its «golden age» characterized by cardinal re-equipment and strengthening of the staff. There appeared the devices of expert class which completely replaced the manual testing process, the work connected with interpretation of serous meningitis outbreaks in Russia and the near abroad became more active.Now the department is a hi-technology scientific and practical center on studying viral and invasive forms of diseases with a priority direction of further innovations in laboratory diagnostics. В статье освещается история становления вирусологической лаборатории с 1963 г. после постановления АМН СССР и Министерства здравоохранения по расширению вирусологических исследований в СССР.Обобщены результаты научно-исследовательской работы по изучению различных инфекций у детей, разработке новых модифицированных подходов к этиологической экспресс-диагностике заболеваний, в том числе внедренных в практику не только самой лаборатории, но и региональных медицинских центров. Благодаря основному направлению исследований лаборатория получила название отдела этиологических методов диагностики. Основной задачей отдела является создание методов и диагностических алгоритмов для точной верификации инфекционных форм и прогноза развития патологического процесса, позволяющих определять направление дальнейшей терапевтической тактики с целью улучшения исходов заболеваний. С 2008 г. для отдела этиологических методов диагностики начался «золотой век», характеризующийся кардинальной модернизацией оборудования, усилением кадрового состава. В отделе появились приборы эксперт-класса, полностью заменившие ручную постановку анализов, активизировалась работа, связанная с расшифровками вспышек серозного менингита в России и ближнем зарубежье.В настоящее время отдел представляет собой высокотехнологичный научно-практический центр по изучению вирусных и инвазивных форм заболеваний с приоритетным направлением дальнейших инноваций в лабораторной диагностике.

СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ ВИРУСОЛОГИЧЕСКОЙ ДИАГНОСТИКИ ПОЛИОМИЕЛИТА

The review presents the data from the literature of our and foreign countries devoted to modern virologic diagnostics of poliomyelitis viruses of 1, 2, and 3 types that is especially topical in connection with WHO program on complete poliomyelitis elimination in the world. There is described the role of laboratory virologic investigations in making the diagnosis of poliomyelitis infection. The classical methods of poliomyelitis viruses detection are given in detail.В обзоре представлены данные иностранной и отечественной литературы, посвященные современной вирусологической диагностике полиомиелитных вирусов 1, 2 и 3 типов, что особенно актуально в связи с программой ВОЗ о полной ликвидации полиомиелита в мире. Показана роль лабораторных вирусологических исследований в постановке диагноза полиомиелитной инфекции. Достаточно подробно рассматриваются классические методы обнаружения полиомиелитных вирусов

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Результаты вирусологического наблюдения за внутриутробными инфекциями в Санкт-Петербурге

The purpose of researchis the determiningthe etiological structure ofintrauterine infections in Saint-Petersburg pediatric patients, pregnant women andinfants born to them using a variety of virological methods.Methods: serum from 164 children aged from 1 month to 14 years with diagnosis of «intrauterine infection». Serum from 80 pregnant women, collected in each trimester (total – 240 samples, their 42 children (at the age of 1–2 and 4–6  months of life, total – 82 samples). Immunoglobulin Mand G (IgM and IgG)to herpes virus type 1, cytomegalovirus (CMV), Toxoplasma gondii, mycoplasma and chlamydia, rubella, Epstein-Barr virus (EBV) and parvovirus B19, as well as IgG avidity,were determined by ELISA in all these samples. Theimmunoblot (Western blot), using the «Immunoblot2000» with test kits from «Euroimmun AG» (Germany), was applied to confirm cases. Statistical analysis wasperformed with theprograms Microsoft Excel, Statistica6.Results: cytomegalovirus, herpes virus 1st type and Epstein-Barr virus infections are dominate in the structure of intrauterine ones (45%, 23% and 14%, respectively). Laboratory evidence ofreactivationof cytomegalovirus (35% ofpregnant womenin the 2nd and/or 3rd trimesters) and acuteparvovirus infection (15% of cases) were found. Specific IgM to cytomegalovirus were detected in 6,2% ofchildren in the firstsix months of life.Conclusions: with the aim of early detection of cytomegalovirus reactivation and acute parvovirus infection it isnecessary to monitor pregnant women with the definition of specific IgM, IgG and avidity IgG. The procedure to using immunoblotting in the diagnosis of intrauterine infectionsneeds to be further study.Цель: определение этиологической структуры ВУИ в Санкт-Петербурге у больных детей, беременных и рожденных ими детей с использованием различных вирусологических методик.Материалы и методы: сыворотки крови 164 детей в возрасте от 1 месяца до 14 лет с диагнозом «внутриутробная инфекция». Сыворотки крови от 80 беременных женщин (в каждом триместре, всего – 240 образцов) и 42 родившихся у них детей (в возрасте 1–2 и 4–6 месяцев, всего – 84 образца). Во всех образцах методом ИФА определяли иммуноглобулины класса M и G (IgМ и IgG) к герпесу 1-го типа, цитомегаловирусной (ЦМВ), токсоплазменной, микоплазменной и хламидийной инфекциям, краснухе, вирусу Эпштейна – Барр (ВЭБ) и парвовирусу В19, а также – авидность IgG антител. Для подтверждения использовали иммуноблоттинг (иммуноблот) на аппарате «Иммуноблот 2000» с использованием тестаборов фирмы Euroimmun AG (Германия). Статистическая обработка результатов проведена с использованием программ Microsoft Excel, Statistica 6.Результаты: в этиологической структуре внутриутробных инфекций доминируют цитомегаловирусная инфекция (45%), инфекция вирусом простого герпеса 1-го типа (23%) и вирусом Эпштейна – Барр (14%). У 35% беременных во 2-м и/или 3-м триместрах обнаруживаются лабораторные признаки реактивации цитомегаловирусной инфекции, в 15% случаев – острой парвовирусной инфекции. Специфические IgM к ЦМВ выявлены у 6,2% детей первых шести месяцев жизни.Выводы: необходимо осуществлять мониторинг беременных с целью своевременного выявления реактивации цитомегаловирусной и острой парвовирусной инфекций с определением специфических IgM, IgG и авидности IgG. Порядок использования иммуноблоттинга в диагностике внутриутробных инфекций нуждается в дальнейшем изучении

Генетические варианты, выявленные у детей с рекуррентными инфекциями

Currently, the most effective way to diagnose hereditary defects of the immune system is molecular genetic research, the results of which are evaluated in conjunction with the data of clinical and laboratory studies.Aims of the sudy: to evaluate the frequency and spectrum of rare genetic variants associated with the development of primary immunodeficiency (PID) in children with recurrent infections.Materials and methods: DNA samples from 113 children with recurrent infections were analyzed by targeted multigene sequencing of 338 PID-associated genes. Results: Pathogenic variants appropriate to the potential diagnosis of PID were identified in 8% of patients. Interestingly, 47.8% of children had variants associated with auto-inflammatory disorders.В настоящее время наиболее эффективным способом диагностики наследственных дефектов иммунной системы является молекулярно-генетическое исследование, результаты которого оцениваются в совокупности с данными клинико-лабораторных исследований.Цель: оценка частоты и спектра редких вариантов генов, ассоциированных с развитием первичных иммунодефицитов (ПИД), у детей с рекуррентными инфекциями.Материалы и методы: Образцы ДНК 113 детей с рекуррентными инфекциями проанализированы методом таргетного высокопроизводительного секвенирования на предмет наличия мутаций в генах ПИД.Результаты: патогенные варианты, соответствующие потенциальному диагнозу ПИД, выявлены у 8% пациентов. У 47,8% детей выявлены варианты генов, ассоциированных с развитием аутовоспалительных заболеваний

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways

Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip (STS) extracts and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. Results: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFN-gamma mRNA in patients with lichenoid (p&lt;0.0001) and psoriasiform dermatitis (p&lt;0.01) as compared to patients without ircAEs, while the highest IL-13 mRNA levels were detected in the eczema (p&lt;0.0001, compared to control). IL-17A mRNA was selectively increased in psoriasiform (p&lt;0.001), lichenoid (p&lt;0.0001), bullous dermatitis (p&lt;0.05) and MPR (p&lt;0.001), compared to control. Distinct cytokine profiles were confirmed in STS and plasma. Analysis determined increased skin/plasma IL-4 cytokine in pruritus, skin IL-13 in eczema, plasma IL-5 and IL-31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2-cytokine targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. Conclusions: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions