Glatiramer Acetate and Nanny Proteins Restrict Access of the Multiple Sclerosis Autoantigen Myelin Basic Protein to the 26S Proteasome

© 2014 Ekaterina Kuzina et al. We recently showed that myelin basic protein (MBP) is hydrolyzed by 26S proteasome without ubiquitination. The previously suggested concept of charge-mediated interaction between MBP and the proteasome led us to attempt to compensate or mimic its positive charge to inhibit proteasomal degradation. We demonstrated that negatively charged actin and calmodulin (CaM), as well as basic histone H1.3, inhibit MBP hydrolysis by competing with the proteasome and MBP, respectively, for binding their counterpart. Interestingly, glatiramer acetate (GA), which is used to treat multiple sclerosis (MS) and is structurally similar to MBP, inhibits intracellular and in vitro proteasome-mediated MBP degradation. Therefore, the data reported in this study may be important for myelin biogenesis in both the normal state and pathophysiological conditions

The role of pioglitazone in the fight against insulin resistance, atherosclerosis, cardiovascular disease, and non-alcoholic fatty liver disease

Modern strategies for the treatment of type 2 diabetes mellitus involve the use of pathogenetically based approaches aimed at achieving optimal glycemic control and its long-term retention. Timely and rational use of 9 classes of hypoglycemic drugs, including as part of combination therapy, makes it possible to achieve significant success in diabetes therapy. One of the fundamental principles in the treatment of type 2 diabetes mellitus is the effect on insulin resistance. For this purpose, two groups of drugs are used: biguanides and thiazolidinediones (glitazones). The action of glitazones is directly related to an increase in the sensitivity of insulin-dependent tissues to insulin and a pronounced decrease in hyperinsulinemia in patients with type 2 diabetes. Of particular interest are the pathways of insulin signal transduction, the mechanisms of insulin resistance, and the possibilities of pathogenetic therapy with thiazolidinediones. Pioglitazone is currently the only available member of the thiazolidinedione class in the world, allowing to expand the management of diabetes mellitus by reducing insulin resistance in muscle and adipose tissue and glucose production by the liver. Its use can have a number of pleiotropic effects, including on cardiovascular diseases and non-alcoholic fatty liver disease, which expands the priorities for choosing hypoglycemic therapy in patients with type 2 diabetes at various stages of therapy

Consumer credit in comparative perspective

We review the literature in sociology and related fields on the fast global growth of consumer credit and debt and the possible explanations for this expansion. We describe the ways people interact with the strongly segmented consumer credit system around the world—more specifically, the way they access credit and the way they are held accountable for their debt. We then report on research on two areas in which consumer credit is consequential: its effects on social relations and on physical and mental health. Throughout the article, we point out national variations and discuss explanations for these differences. We conclude with a brief discussion of the future tasks and challenges of comparative research on consumer credit.Accepted manuscrip

Evaluation of the quality of the educational process at the departments of USMU in the opinion of the residents

This article describes the quality control problems Postgraduate residency programs at the Urals State Medical University. The evaluation was conducted by questionnaire residents. Quality evaluation system of graduate training of USMU is designed on the basis of existing legislative acts in the field of higher education and local acts regulating the activities of the university education and training of students mastering basic undergraduate programs, specialties, masterв данной статье рассмотрены проблемы контроля качества постдипломного образования по программам ординатуры в Уральском государственном медицинском университете. Оценка проводилась путем анкетирования ординаторов. Система оценки качества подготовки выпускников УГМУ разработана на основе действующих законодательных актов в сфере высшего образования и локальных актов, регламентирующих образовательную деятельность университета и обучение студентов, осваивающих основные программы бакалавриата, специалитета, магистратуры

Analysis of the structure of postoperative recerrence of varicose veins of the lower extremities and the choice of tactics for their correction

The purpose of the study was to study the structure of recurrences of varicose veins of the lower extremities after endovasal laser coagulation and tactics of management of patients with recurrences.Цель исследования – изучить структуру рецидивов варикозной болезни нижних конечностей после проведения эндовазальной лазерной коагуляции и тактику ведения пациентов с рецидивами

Light regulation of metabolic pathways in fungi

Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes

Эффективность и безопасность применения цепэгинтерферона альфа 2b в составе двойной (цепэгинтерферон альфа 2b и рибавирин) и тройной (симепревир, цепэгинтерферон альфа 2b и рибавирин) схемы противовирусной терапии у пациентов с хроническим гепатитом С. Опыт реальной клинической практики

The objective. To evaluate the efficacy, safety and tolerability of double (cepeginterferon alfa-2b and ribavirin) and triple (simeprevir, cepeginterferon alfa 2b and ribavirin) treatment regimens in chronic hepatitis C patients in everyday clinical practice of the Hepatology Center in Clinical Infectious Diseases Hospital in Moscow.Materials and methods. From 2013 to 2015 a total of 289 patients with chronic hepatitis C received antiviral therapy with cepeginterferon alfa 2b. 267 patients received combination of cepeginterferon alfa 2b and ribavirin. 22 patients received triple antiviral therapy with simeprevir, cepeginterferon alfa 2b and ribavirin. Treatment efficacy was assessed by the rate of sustained virologic response on 12/24 week after completion of antiviral therapy (SVR 12/24). In safety analysis all 289 patients were included. All cases of deterioration of the patient’s condition and laboratory abnormalities were registered throughout the treatment period and follow up.Results. 267 patients (74,5%, n=199, with 2/3 genotype, 25,5%, n = 68, with 1 genotype) received cepeginterferon alfa 2b 1,5 µg/kg/week and ribavirin 800-1400 daily (weight based). 22 patients with genotype 1 (the majority of them had advanced fibrosis (F3-F4) underwent triple therapy with simeprevir 150 mg once daily in combination with cepeginterferon alfa 2b 1,5 µg/kg/week and ribavirin 800-1400 mg daily (weight based) for 12 weeks, followed by cepeginterferon alfa 2b/ ribavirin therapy for 12-36 weeks. SVR was observed in 85,6% (n=113) of genotype 2/3 infected patients and in 64,6% (n=31) of genotype 1 infected patients. Among patients with mild or moderate fibrosis SVR rate was 90,7% in genotype 2/3 patients and 75% in genotype 1 patients. 21 patient completed the course of triple therapy. SVR was observed in 71,4% (n=15) of patients. Registered adverse reactions were common for interferon/ribavirin based therapy. In most cases adverse events were moderate and matched grade 1-2 of CTCAE.Conclusion. The present experience confirms the efficacy and safety of double therapy including cepeginterferon alfa 2b and ribavirin in genotype 1 and 2/3 infected patients. The use of this regimen is reasonable in patients who don’t have negative predictive factors of response to interferon-based therapy. In patients with genotype 1 HCV and/or advanced fibrosis (F3-F4) adding of simeprevir to the cepeginterferon alfa/ribavirin combination reduces the duration of treatment, improves the efficacy, while maintaining a good safety profile.Цель: оценить эффективность, безопасность и переносимость применения цепэгинтерферона альфа 2b в составе двойной (цепэгинтерферон альфа 2b и рибавирин) и тройной (симепревир, цепэгинтерферон альфа 2b и рибавирин) схем противовирусной терапии у пациентов с хроническим гепатитом С в реальной клинической практике.Материалы и методы. C 2013 по 2015 г. в Центре по лечению хронических вирусных гепатитов Инфекционной клинической больницы № 1 г. Москвы 289 пациентов с хроническим гепатитом С получали противовирусную терапию (ПВТ) схемами, включавшими цепэгинтерферон альфа 2b. 267 пациентов получали цепэгинтерферон альфа 2b и рибавирин. 22 пациентам была назначена тройная схема ПВТ (симепревир, цепэгинтерферон альфа 2b и рибавирин). Эффективность лечения определялась частотой достижения вирусологического ответа через 12/24 недели после окончания терапии (УВО 12/24). В анализ безопасности включены все пациенты, получавшие цепэгинтерферон альфа 2b (n=289).Результаты. 267 пациентов (74,5% (n=199) пациентов – 2/3 генотип, 25,5% (n=68) пациентов – 1 генотип HCV) получали цепэгинтерферон альфа 2b 1,5 мкг/кг/ нед. и рибавирин 800–1400 мг/сут. 22 пациентам с 1 генотипом (у большинства из них имелся фиброз F3–F4) был назначен симепревир 150 мг/сут, цепэгинтерферон альфа 2b 1,5 мкг/кг/нед, рибавирин 800–1400 мг/сут в течение 12 недель, далее цепэгинтерферон альфа 2b и рибавирин в течение 12/36 недель.При применении двойной схемы ПВТ УВО достигли 85,6% (n=113) пациентов с 2/3 генотипом и 64,6% (n=31) пациентов с 1 генотипом HCV. Среди пациентов с фиброзом F1–F2 УВО зафиксирован у 90,7% пациентов с 2/3 генотипом HCV и у 75% с 1 генотипом HCV. Курс лечения тройной схемой терапии завершил 21 пациент, УВО достигли 71,4% (n=15) пациентов.Зафиксированные нежелательные явления были характерны для применявшихся режимов терапии. В большинстве случаев реакции были незначительно или умеренно выражены.Заключение. Опыт реальной клинической практики показал, что применение двойной схемы ПВТ (цепэгинтерферон альфа 2b и рибавирин) эффективно и безопасно у пациентов как с 1, так и со 2/3 генотипами HCV. Оправдано назначение такой терапии пациентам, не имеющим предикторов неблагоприятного ответа на лечение. Добавление к комбинации цепэгинтерферона альфа 2b и рибавирина симепревира позволяет повысить эффективность терапии и сократить ее длительность при сохранении хорошего профиля безопасности у пациентов с 1 генотипом HCV и более продвинутыми стадиями заболевания

Recent advances of metabolomics in plant biotechnology

Biotechnology, including genetic modification, is a very important approach to regulate the production of particular metabolites in plants to improve their adaptation to environmental stress, to improve food quality, and to increase crop yield. Unfortunately, these approaches do not necessarily lead to the expected results due to the highly complex mechanisms underlying metabolic regulation in plants. In this context, metabolomics plays a key role in plant molecular biotechnology, where plant cells are modified by the expression of engineered genes, because we can obtain information on the metabolic status of cells via a snapshot of their metabolome. Although metabolome analysis could be used to evaluate the effect of foreign genes and understand the metabolic state of cells, there is no single analytical method for metabolomics because of the wide range of chemicals synthesized in plants. Here, we describe the basic analytical advancements in plant metabolomics and bioinformatics and the application of metabolomics to the biological study of plants