Metabolic cardioprotection: new concepts in implementation of cardioprotective effects of meldonium

Recent studies confirm the need to find means to correct ischemic / reperfusion injury due to the hemodynamic medicine, which are already known do not have the proper cardioprotective effects. Key issue is the possibility of drug effects on the mitochondria of cardiomyocytes that controls the aerobic metabolism and maintenance of ATP admission into cardiomyocyte

Study of dose-dependent effect of 2-ethyl-6-methyl-3 hydroxypyridine succinate on the contractile function of isolated rat heat

In experiments on the isolated rat heart there were studied the effects of different doses (21.43 mg/kg/day and 85 . 72 mg/kg/day) 2-ethyl-6-methyl-3 hydroxypy ridine succinate ("EkoPharmInvest", Russia), on the contractile function of isolated hearts subjected to prior doxorubicin model (20 mg/kg, intraperitoneal) of pathology. The dynamic of the power mechanisms of ion transport was evaluated by imposing high h eart rate (480 BPM) and increase concentration of Са2+ to 5 mmol in perfusat

Pharmacological correction of L-NAME-induced oxide deficiency with derivatives of 3-(2,2,2-trimethylhydrazinium) propionate

This paper deals with the study of correction of L-NAME-induced endothelial dysfunction by means of 3-(2,2,2-trimethylhydrazinium) propionate derivative

Immunomodulatory properties of recombinant human granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a myelopoietic growth factor that exerts pleiotropic effect not only on the differentiation of immature progenitor cells into polymorphonuclear neutrophils, monocytes/macrophages and dendritic cells, but also controls the functioning of differentiated cells. GM-CSF is currently being investigated in clinical trials as an immunomodulator and adjuvant. However, a wide range of biological activities and, sometimes, paradoxical effects of this cytokine require more thorough studies of its action, in order to predict its efficacy under different conditions of immunotherapy. In this work, we have studied the effect of recombinant human GM-CSF on metabolic activity of mouse peritoneal exudate cells in primary cell cultures. Metabolic (redox) activity of the cells was assessed by their ability to reduce nitroblue tetrazolium (NBT) in the course of MF- and Fc-dependent phagocytosis triggered by addition of opsonized zymosan, or sheep erythrocytes to the culture medium. We have shown the dose-dependent stimulatory effect of GM-CSF on the oxidative metabolism of phagocytic peritoneal macrophages and neutrophils. Upon culturing the pepton-elicited cells at wide range of GM-CSF concentrations (5 to 40,000 ng/mL) for 2 and 24 hours, a more pronounced effect of the substance was observed for neutrophils. The GM-CSF preparation caused a significant increase (by 13-17%) in the redox activity of neutrophils induced by opsonized zymosan that persisted at a low dose range, and was retained after 24 hours. The stimulatory effect of GM-CSF on macrophages with NBT index increase by 16% was observed in the short-term cultures. In general, the elicited cells of both types showed a more pronounced response to lower concentrations of GM-CSF (5-125 ng/mL), and weaker effect at higher doses of the preparation. A similar dependence was found when studying the resident macrophages. Culturing of resident cells with GM-CSF at the doses of 5,000 to 40,000 ng/mL for 24 hours caused a significantly increased redox activity of the cells induced by zymosan, or sheep erythrocytes (by 33-52%). In both cases, the maximal response was detected at a dose of 5,000 ng/mL and decreased with increasing dose. The stimulatory effect of GM-CSF upon resident macrophages was more pronounced as compared to elicited cells, which was characterized by the prolonged period of cell activation (up to 24 hours of culture). The data obtained are of interest, in view of prospective usage of GM-CSF as a component of immunomodulatory and adjuvant therapy for various infectious diseases

Expression of the chloroplast genome: modern concepts and experimental approaches

A unique feature of plants is the presence of two extranuclear genomes, chloroplasts and mitochondria. The chloroplast genome is relatively small, 100–120 genes, which encode less than 5 % of all proteins required for plastids to function. The cpDNA expression retains prokaryotic features, cotranscription in the operon, bacteria-like RNA polymerases and promoters, 70S ribosomes etc., also new characters appear such as uncoupling of transcription with translation, phage-type RNA polymerases, RNA editing, and splicing of primary transcripts. The interaction of the nucleus (nuclear genomes) and cytoplasm (plastid and mitochondrial genes) during plant development is necessary for proper development and adaptation to the environment. The aim of this review is to disclose the peculiarities of plastid genome expression. The way the genetic information in chloroplasts is used (transcription, editing, splicing, polyadenylation and translation) is consequently described. Furthermore, the importance of all expression machinery components in plant life is discussed. Modern approaches for RNA pool study are described and critical points of nuclear-cytoplasmic interaction in the functions of chloroplasts are revealed. The information about the most important factors of nuclear-cytoplasmic signaling in higher plants (sigma factors and PPR proteins encoded by the nucleus) are reviewed. Thus, the multilevelness and viability of plastid genome expression regula­tion in plant cells and interdependence of the pro­cesses in different compartments is proved. A summary of the latest studies of the expression of the plastid genome using genetic chips (microarrays, macroarrays) is provided. Original results are presented

Pharmacological preconditioning by incretinomimetics exenatide and vildagliptin: decrement of liver ischemia-reperfusion injury

Study of hepatoprotective activity of exenatide and vildagliptin on the liver ischemia/reperfusion model, taking into account biochemical and morphological parameter

Physical properties of thermoelectric zinc antimonide using first-principles calculations

We report first principles calculations of the structural, electronic, elastic and vibrational properties of the semiconducting orthorhombic ZnSb compound. We study also the intrinsic point defects in order to eventually improve the thermoelectric properties of this already very promising thermoelectric material. Concerning the electronic properties, in addition to the band structure, we show that the Zn (Sb) crystallographically equivalent atoms are not exactly equivalent from the electronic point of view. Lattice dynamics, elastic and thermodynamic properties are found to be in good agreement with experiments and they confirm the non equivalency of the zinc and antimony atoms from the vibrational point of view. The calculated elastic properties show a relatively weak anisotropy and the hardest direction is the y direction. We observe the presence of low energy modes involving both Zn and Sb atoms at about 5-6 meV, similarly to what has been found in Zn4Sb3 and we suggest that the interactions of these modes with acoustic phonons could explain the relatively low thermal conductivity of ZnSb. Zinc vacancies are the most stable defects and this explains the intrinsic p-type conductivity of ZnSb.Comment: 33 pages, 8 figure

Experimental constraints on the ordinary chondrite shock darkening caused by asteroid collisions

Context. Shock-induced changes in ordinary chondrite meteorites related to impacts or planetary collisions are known to be capable of altering their optical properties. Thus, one can hypothesize that a significant portion of the ordinary chondrite material may be hidden within the observed dark C/X asteroid population. Aims. The exact pressure-temperature conditions of the shock-induced darkening are not well constrained. Thus, we experimentally investigate the gradual changes in the chondrite material optical properties as a function of the shock pressure. Methods. A spherical shock experiment with Chelyabinsk LL5 was performed in order to study the changes in its optical properties. The spherical shock experiment geometry allows for a gradual increase of shock pressure from similar to 15 GPa at a rim toward hundreds of gigapascals in the center. Results. Four distinct zones were observed with an increasing shock load. The optical changes are minimal up to similar to 50 GPa. In the region of similar to 50-60 GPa, shock darkening occurs due to the troilite melt infusion into silicates. This process abruptly ceases at pressures of similar to 60 GPa due to an onset of silicate melting. At pressures higher than similar to 150 GPa, recrystallization occurs and is associated with a second-stage shock darkening due to fine troilite-metal eutectic grains. The shock darkening affects the ultraviolet, visible, and near-infrared region while changes to the MIR spectrum are minimal. Conclusions. Shock darkening is caused by two distinct mechanisms with characteristic pressure regions, which are separated by an interval where the darkening ceases. This implies a reduced amount of shock-darkened material produced during the asteroid collisions.Peer reviewe

Changes in the antigenic and genetic structure of influenza viruses: analysis of surveillance data of influenza A and B in Russia in 2006-2013

The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses.The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals.Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013.The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses. The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals. Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013