Взаимосвязь лабораторных биомаркеров и ультразвуковых признаков воспаления у пациентов с ревматоидным артритом на фоне терапии биоаналогом ритуксимаба

Objective: to assess the relationship between laboratory biomarkers and ultrasonographic signs of inflammation in patients with rheumatoid arthritis during therapy with a rituximab (RTM) biosimilar.Patients and methods. 20 patients with definite diagnosis of RA were examined. All patients received 2 infusions of RTM (Acellbia®), at a dose of 600 mg intravenously 2 weeks apart during therapy with methotrexate, non-steroidal anti-inflammatory drugs and glucocorticoids. Clinical and laboratory parameters were analyzed immediately before the start of therapy, and then 12 and 24 weeks after the first infusion of the drug.Results and discussion. By the 24th week of RTM therapy, a good/moderate effect according to the EULAR criteria was registered in 17 (85%) patients; remission according to DAS28 (<2.6) was achieved in 4 (20%) patients, SDAI (≤3.3) – in 2 (10%), CDAI (≤2.8) – in 1 (5%). Prior to the start of treatment, active synovitis was detected in 13 (65%) patients by power Doppler imaging (PD), and in 20 (100%) patients by gray scale scanning. During therapy with the RTM biosimilar, a significant decrease in inflammatory changes in the joints was observed, and by the 24th week after the start of treatment, the median PD was 0.5; active inflammation persisted in 7 (35%) patients. As shown by ROC analysis, the initial level of interleukin (IL) 6 >100.0 pg/ml is associated with the persistence of inflammatory activity according to PD by the 24th week of therapy with the RTM biosimilar, while the sensitivity was 85% and the specificity was 62% (AUC 0.78, 95% CI 0.57–0.99)Conclusion. An association was found between an increased level of pro-inflammatory cytokines, mainly IL6, and the activity of synovial inflammation according to ultrasound data. IL6 is the most promising marker for predicting persistent inflammatory activity based on the results of PD; other analyzed parameters have worse sensitivity and specificity parameters.Цель исследования – оценить взаимосвязь лабораторных биомаркеров и ультразвуковых признаков воспаления у пациентов с ревматоидным артритом на фоне терапии биоаналогом ритуксимаба (РТМ).Пациенты и методы. Обследовано 20 больных с достоверным диагнозом РА. Всем пациентам проведено по 2 инфузии РТМ (Ацеллбия®) в дозе 600 мг внутривенно с интервалом в 2 нед на фоне терапии метотрексатом, нестероидными противовоспалительными препаратами и глюкокортикоидами. Клинические и лабораторные показатели анализировались непосредственно перед началом терапии, а затем через 12 и 24 нед после первой инфузии препарата.Результаты и обсуждение. К 24-й неделе терапии РТМ хороший/умеренный эффект по критериям EULAR зарегистрирован у 17 (85%) пациентов; ремиссия по DAS28 (<2,6) достигнута у 4 (20%) больных, SDAI ( ≤3,3) – у 2 (10%), CDAI ( ≤2,8) – у 1 (5%). До начала лечения активный синовит по данным энергетического допплеровского картирования (ЭД) выявлен у 13 (65%) пациентов, а при сканировании в режиме серой шкалы – у 20 (100%). На фоне терапии биоаналогом РТМ наблюдалось значимое уменьшение воспалительных изменений в суставах, и к 24-й неделе после начала лечения медиана ЭД составила 0,5; активное воспаление сохранялось у 7 (35%) больных. Как показал ROC-анализ, исходный уровень интерлейкина (ИЛ) 6 >100,0 пг/мл ассоциируется с сохранением воспалительной активности по данным ЭД к 24-й неделе терапии биоаналогом РТМ, при этом чувствительность составила 85% и специфичность – 62% (AUC 0,78, 95% доверительный интервал 0,57–0,99)Заключение. Выявлена ассоциация между повышенным уровнем провоспалительных цитокинов, в основном ИЛ6, и активностью синовиального воспаления по данным УЗИ. Для прогнозирования сохраняющейся воспалительной активности по результатам ЭД наиболее перспективным маркером является ИЛ6, другие анализируемые показатели имеют худшие параметры чувствительности и специфичности

Clinical application of induced sputum in children with newly diagnosed asthma: cellular and immunologic characteristics

Authors investigate cells and immunologic factors of induced sputum in children with newly diagnosed asthma and healthy children without atopy. The aim of the study was to find out the differences of cellular and immunologic profiles of induced sputum in children with newly diagnosed asthma. 35 children aged 1,5-5 years old (Me = 3,5 years) were include in this study: 18 children with newly diagnosed asthma and 17 children (control group) without allergic diseases, which had no respiratory symptoms during last month. Sputum induction carried out according to our modification of protocol developed by Pin et al. The levels of IgE, slgA, lgG4, IL-1β, IL-4, IL-8, IL-13, TNFα, INFγ, N03, NOX and cells percentage (macrophages, neutrophils, eosinophils, lymphocytes) were evaluated in sputum. Results. The percentage of eosinophils was significantly higher and the percentage of macrophages was significantly lower in induced sputum of children with newly diagnosed asthma. The levels of proinflammatory factors (IL-1β, IL-4, IL-8, IL-13, TNFα), immunoglobulins, which participate in allergic inflammation (IgE, slgA, lgG4) and stable metabolites of NO (NO3, NOX) in sputum were also significantly higher in children with newly diagnosed asthma.Проводился подсчет клеток и определение иммунологических факторов в индуцированной мокроте у детей с вперсые выявленной бронхиальной астмой и здоровых детей без атопии. Целью исследования было выявление цитоиммунологических особенностей индуцированной мокроты у детей раннего возраста с впервые выявленной бронхиальной астмой. В исследовании приняли участие 35 детей в возрасте 1,5-5 лет (средний возраст 3,5г.): 18 детей с впервые выявленной бронхиальной астмой и 17 практически здоровых детей без атопии - контрольная группа. У всех детей в исследовании в течение предшествующего месяца не было зарегистрировано эпизодов респираторной инфекции. Индукция мокроты проводилась по модифицированному нами протоколу с использованием гипертонического раствора хлорида натрия. Прототипом явился метод, разработанный Pin et al., исследовался клеточный состав (%) (макрофаги, нейтрофилы, эозинофилы, лимфоциты) и иммунологический профиль (IgE, slgA, lgG4, IL-1β, IL-4, IL-8, IL-13. TNFα, INFγ, NO3, NOX) индуцированной мокроты. Результаты. У детей с впервые выявленной бронхиальной астмой в индуцированной мокроте уровень эозинофилов (%) достоверно выше, а уровень макрофагов (%) достоверно ниже по сравнению со здоровыми детьми без атопии. Так же у детей с бронхиальной астмой выявлены более высокие концентрации провоспалительных цитокинов (ФНОа, ИЛ 4, IL-1B, ИЛ8, ИЛ 13), иммуноглобулинов (IgE, lgG4) участвующих в аллергическом воспалении бронхов при бронхиальной астме и конечных стабильных метаболитов оксида азота (NO3, NOX) по сравнению с показателями здоровых детей без атопии

Microaspiration in GER as one of the causes of bronchial asthma exacerbation and the occurrence of chronic cough in children. History of the problem and diagnostics

The purpose of the review: to analyze the evolution of the views of clinicians and researchers on the relationship between gastroesophageal reflux and its extraesophageal bronchial manifestations, and the stages of the formation of the diagnosis of microaspiration of the lower respiratory tract in children. Materials and methods. Search in electronic databases: Elibrary, Federal Electronic Medical Library of the Ministry of Health of the Russian Federation, bibliographic database of articles on medical sciences, created by the US National Library of Medicine MEDLINE.Цель обзора: проанализировать эволюцию взглядов клиницистов и исследователей на взаимосвязь гастроэзофагального рефлюкса и его внепищеводных бронхиальных проявлений, и этапы становления диагностики микроаспирации нижних дыхательных путей у детей

Skeletal Muscle-Specific Ablation of γcyto-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γcyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γcyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γcyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γcyto-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests γcyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a γcyto-actin-utrophin interaction

Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes

Lis1-Nde1 integrates cerebral cortical neurogenesis with neuronal migration by stabilizing the basal-lateral surface of radial glial cells

Myosin binding protein C: implications for signal-transduction

Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure

Manpower restructuring in the Ural enterprises: management rhetoric and practice of internal career permutations

This article analyzes changes in personnel policy in industrial enterprises. Focus of attention - the internal labor market, the factors of internal mobility. The basis of analysis - a research, conducted in April-July 2009, the case studies on two of the Ural enterprises. The article presents data on the dynamics of internal mobility and changes in the declared purposes of personnel policy of enterprise restructuring stages. This article contains the typical model of intra-organizational mobility and career of rearrangements at different enterprise restructuring stages.Статья посвящена анализу изменений кадровой политики на промышленных предприятиях. Фокус внимания - внутренний рынок труда, факторы внутренней мобильности. В основе выводов - исследование, выполненное в апреле-июле 2009 г., кейс-стади на двух уральских предприятиях. В статье приведены данные о динамике внутренней мобильности в связи с этапами реструктуризации предприятий и изменениями в декларируемых целях кадровой политики. Рассмотрены типические модели внутриорганизационной мобильности и карьерных перестановок на разных этапах реструктуризации предприятий

Case study of financing of innovative projects and exogenous shocks

One of the main problem of innovative projects in Russian Federation is the need to assess the impact of exogenous shocks on their financing and development. The impact of this type of shock in the period of globalization is sharply increasing. In order to assess the impact of exogenous shocks on innovative projects we create a model with two stages using the innovate project of production of water purification plants. The first stage of it is the construction of a simple model of financial risk, stipulating the conditions when investors will invest in this firm in the absence of negative shocks, their expectations will depend on their own confidence in continuing investment at the next stages. This model shows a positive result. At the second stage we take into account the impact of the negative exogenous shocks on the project, and try to trace a reaction of companies involved in financing innovative projects. The results of the project were negative. The investor in this case as a rule can stop financing and has the risk of losses. In order to prevent this situation we propose to use a real option for a possible refusal to implement an innovative project in the event that the net present value after one year of financing will be negative or very small. To our opinion it is one of the best ways to reduce financial risks during the implementation of innovative projects for investors