Russian National Research Medical University
Moscow, Russia
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Ignatov A.M.,Russian National Research Medical University
Plasma Physics Reports | Year: 2017

The theory of van Kampen waves in plasma with an arbitrary anisotropic distribution function is developed. The obtained solutions are explicitly expressed in terms of the permittivity tensor. There are three types of perturbations, one of which is characterized by the frequency dependence on the wave vector, while for the other two, the dispersion relation is lacking. Solutions to the conjugate equations allowing one to solve the initial value problem are analyzed. © 2017, Pleiades Publishing, Ltd.

Khan O.,Wayne State University | Rieckmann P.,University of Bamberg | Boyko A.,Russian National Research Medical University | Selmaj K.,Medical University of Lódz | Zivadinov R.,State University of New York at Buffalo
Annals of Neurology | Year: 2013

Objective To assess the efficacy and safety of glatiramer acetate (GA) 40mg administered 3× weekly (tiw) compared with placebo in patients with relapsing-remitting multiple sclerosis (RRMS). Methods This randomized, double-blind study was conducted in 142 sites in 17 countries. Patients with RRMS with at least 1 documented relapse in the 12 months before screening, or at least 2 documented relapses in the 24 months before screening, and an Expanded Disability Status Scale score ≤ 5.5, were randomized 2:1 to receive either subcutaneous (sc) GA 40mg tiw (1ml) or placebo for 12 months. Results Of 1,524 patients screened, 1,404 were randomized to receive GA 40mg sc tiw (n = 943) or placebo (n = 461). Ninety-three percent and 91% of patients in the placebo and GA groups, respectively, completed the 12-month study. GA 40mg tiw was associated with a 34.0% reduction in risk of confirmed relapses compared with placebo (mean annualized relapse rate = 0.331 vs 0.505; p < 0.0001). Patients who received GA 40mg tiw experienced highly significant reduction (p < 0.0001) in the cumulative number of gadolinium-enhancing T1 (44.8%) and new or newly enlarging T2 lesions (34.7%) at months 6 and 12. GA 40mg tiw was safe and well tolerated. The most common adverse events in the GA group were injection site reactions (35.5% with GA vs 5.0% with placebo). Interpretation GA 40mg sc tiw is a safe and effective regimen for the treatment of RRMS, providing the convenience of fewer sc injections per week. © 2013 American Neurological Association.

Belmer S.V.,Russian National Research Medical University
Voprosy Detskoi Dietologii | Year: 2016

The theory of food (nutritional) programming has been recently causing much interest. The basic ideas of this theory have been known for a long time, but only in the past decades they, supported by the findings of research works, have taken shape as a single scientific conception. Nutritional programming presupposes that the character of a child's nutrition in the critical periods of life predetermines (programmes) the specificities of metabolism during the whole life and, consequently, predisposition to certain diseases and their specific course. First of all, the intrauterine period and the first 12 months after birth are of interest. As has been shown by many studies, the character of foetal nutrition during the intrauterine period, one of the indicators of which is the birth weight, plays a very important role in the long-term prognosis of the state of health. As has been found, low body weight at birth and at the age of 12 months is associated with a high risk for cardiovascular disorders in adults, high arterial blood pressure, impaired glucose tolerance, type 2 diabetes mellitus, metabolic syndrome, higher blood levels of cholesterol and coagulation factor VII. The character of intrauterine nutrition influences the health of children and adults in the long-term perspective. Adequate nutrition of the foetus is a key health factor for the whole life.

Seplyarskiy V.B.,Russian National Research Medical University | Andrianova M.A.,Russian National Research Medical University | Bazykin G.A.,Russian National Research Medical University
Genome Research | Year: 2017

APOBEC3A/B cytidine deaminase is responsible for the majority of cancerous mutations in a large fraction of cancer samples. However, its role in heritable mutagenesis remains very poorly understood. Recent studies have demonstrated that both in yeast and in human cancerous cells, most APOBEC3A/B-induced mutations occur on the lagging strand during replication and on the nontemplate strand of transcribed regions. Here, we use data on rare human polymorphisms, interspecies divergence, and de novo mutations to study germline mutagenesis and to analyze mutations at nucleotide contexts prone to attack by APOBEC3A/B. We show that such mutations occur preferentially on the lagging strand and on nontemplate strands of transcribed regions. Moreover, we demonstrate that APOBEC3A/B-like mutations tend to produce strand-coordinated clusters, which are also biased toward the lagging strand. Finally, we show that the mutation rate is increased 3′ of C→G mutations to a greater extent than 3′ of C→T mutations, suggesting pervasive trans-lesion bypass of the APOBEC3A/B-induced damage. Our study demonstrates that 20% of C→T and C→G mutations in the TpCpW context-where W denotes A or T, segregating as polymorphisms in human population-or 1.4% of all heritable mutations are attributable to APOBEC3A/B activity. © 2017 Seplyarskiy et al.

Pustovit K.B.,Russian National Research Medical University | Kuzmin V.S.,Russian National Research Medical University | Abramochkin D.V.,Russian National Research Medical University
Naunyn-Schmiedeberg's Archives of Pharmacology | Year: 2016

Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart. © 2015 Springer-Verlag Berlin Heidelberg.

Ivanov S.M.,Russian National Research Medical University | Lagunin A.A.,Russian National Research Medical University | Poroikov V.V.,Russian National Research Medical University
Drug Discovery Today | Year: 2016

During recent years, various in silico approaches have been developed to estimate chemical and biological drug features, for example chemical fragments, protein targets, pathways, among others, that correlate with adverse drug reactions (ADRs) and explain the associated mechanisms. These features have also been used for the creation of predictive models that enable estimation of ADRs during the early stages of drug development. In this review, we discuss various in silico approaches to predict these features for a certain drug, estimate correlations with ADRs, establish causal relationships between selected features and ADR mechanisms and create corresponding predictive models. © 2015 Elsevier Ltd. All rights reserved.

Alipieva K.,Bulgarian Academy of Science | Korkina L.,Russian National Research Medical University | Orhan I.E.,Gazi University | Georgiev M.I.,Bulgarian Academy of Science
Biotechnology Advances | Year: 2014

Phenylethanoid glycosides are naturally occurring water-soluble compounds with remarkable biological properties that are widely distributed in the plant kingdom. Verbascoside is a phenylethanoid glycoside that was first isolated from mullein but is also found in several other plant species. It has also been produced by in vitro plant culture systems, including genetically transformed roots (so-called 'hairy roots'). Verbascoside is hydrophilic in nature and possesses pharmacologically beneficial activities for human health, including antioxidant, anti-inflammatory and antineoplastic properties in addition to numerous wound-healing and neuroprotective properties. Recent advances with regard to the distribution, (bio)synthesis and bioproduction of verbascoside are summarised in this review. We also discuss its prominent pharmacological properties and outline future perspectives for its potential application. © 2014 Elsevier Inc.

Buchachenko A.L.,Moscow State University | Orlov A.P.,Russian National Research Medical University | Kuznetsov D.A.,Moscow State University | Breslavskaya N.N.,RAS Institute of Chemistry
Nucleic Acids Research | Year: 2013

Magnetic isotope and magnetic field effects on the rate of DNA synthesis catalysed by polymerases β with isotopic ions 24Mg2+, 25Mg2+ and 26Mg2+ in the catalytic sites were detected. No difference in enzymatic activity was found between polymerases β carrying 24Mg2+ and 26Mg2+ ions with spinless, non-magnetic nuclei 24Mg and 26Mg. However, 25Mg2+ ions with magnetic nucleus 25Mg were shown to suppress enzymatic activity by two to three times with respect to the enzymatic activity of polymerases β with 24Mg2+ and 26Mg2+ ions. Such an isotopic dependence directly indicates that in the DNA synthesis magnetic mass-independent isotope effect functions. Similar effect is exhibited by polymerases β with Zn2+ ions carrying magnetic 67Zn and non-magnetic 64Zn nuclei, respectively. A new, ion-radical mechanism of the DNA synthesis is suggested to explain these effects. Magnetic field dependence of the magnesium-catalysed DNA synthesis is in a perfect agreement with the proposed ion-radical mechanism. It is pointed out that the magnetic isotope and magnetic field effects may be used for medicinal purposes (trans-cranial magnetic treatment of cognitive deceases, cell proliferation, control of the cancer cells, etc). © 2013 The Author(s). Published by Oxford University Press.

Terentiev A.A.,Russian National Research Medical University | Moldogazieva N.T.,Russian National Research Medical University
Tumor Biology | Year: 2013

Alpha-fetoprotein (AFP) is a major mammalian embryo-specific and tumor-associated protein that is also present in small quantities in adults at normal conditions. Discovery of the phenomenon of AFP biosynthesis in carcinogenesis by G. Abelev and Yu. Tatarinov 50 years ago, in 1963, provoked intensive studies of this protein. AFPs of some mammalian species were isolated, purified and physico-chemically and immunochemically characterized. Despite the significant success in study of AFP, its three-dimensional structure, mechanisms of receptor binding along with a structure of the receptor itself and, what is the most important, its biological role in embryo- and carcinogenesis remain still obscure. Due to difficulties linked with methodological limitations, research of AFP was to some extent extinguished by the 1990s. However, over the last decade a growing number of investigations of AFP and its usage as a tumor-specific biomarker have been observed. This was caused by the use of new technologies, primarily, computer-based and genetic engineering approaches in studying of this very important oncodevelopmental protein. Our review summarizes efforts of different scientific groups throughout the world in studying AFP for 50 years with emphasis on detailed description of recent achievements in this field. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Abramochkin D.V.,Russian National Research Medical University | Lozinsky I.T.,Russian National Research Medical University | Kamkin A.,Russian National Research Medical University
Journal of Molecular and Cellular Cardiology | Year: 2014

Cardiac fibroblasts are an essential component of cardiac tissue. These cells not only produce the extracellular matrix, but also are electrically and mechanically coupled with cardiomyocytes. In this way, fibroblasts can influence the electrical activity of cardiomyocytes. Cardiac fibroblasts cannot generate action potentials, but their membrane potential is controlled by mechanical stretch or compression of the surrounding myocardium which in turn affects their interaction with myocytes and the way myocytes respond to mechanical stress. This review discusses the electrical properties of cardiac fibroblasts, the present evidence of fibroblast-myocyte coupling and the way in which these cells respond to mechanical stress. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium.". © 2013 Elsevier Ltd.

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