Influence of thidiazuron on morphogenesis of leaf explants of Betula pubescens Ehrh. in culture in vitro

In the work, the dependence of the morphogenic and regenerative activity of leaf explants of Betula pubescens on their way of orientation on the nutrient medium and on the presence of thidiazuron in the medium is studied. Methods: cell culture in vitro; statistical analysis. The results obtained on the Betula pubescens (clone 3f1) indicate a high regenerative activity of the studied genotype. High growth-producing ability of thidiazuron in a concentration of 0,1–0,5 mg/l was noticed. It is shown that the orientation of the leaf blade on the medium can have a significant effect on the number of adventitious buds and shoots on the leaf and the frequency of regeneration, depending on the concentration of thidiazuron. Root formation was noticed in the 100% of explants cultured on a medium without hormones, when the leaf was adaxially placed on the medium. The percentage of rhizogenesis on leaf explants cultivated on media containing thidiazuron ranged from 17 to 57. There were from 1 to 7 roots of different length on the leaves. Differentiation of adventitious buds and shoots from callus tissue formed over the entire surface of the explant, and the development of adventitious kidneys induced in the first passage occurred in 76,7–100 % of explants in almost all experimental variants. A tendency has been revealed: most of the adventitious buds and shoots are formed on the side of the leaf blade that contacts the medium. The number of adventitious buds and shoots on the explants ranged from 1 to 50, depending on the concentration of thidiazuron in the first passage

Drugs influencing on PCSK9 activity: modelling of efficacy in patients who had myocardial infarction with uncontrolled dyslipidemia

Cardiovascular diseases are the leading cause of death worldwide. It is possible to influence the development of these diseases by influencing their main pathogenetic link — dyslipidemia.Aim: to evaluate, using the example of alirocumab, the potential effect of drugs affecting the activity of PCSK9 on the achievement of goals for the prevention of the development of cardiovascular diseases and cardiovascular complications in patients of working age who had an acute myocardial infarction (MI) less than a year ago, with uncontrolled dyslipidemia.Materials and methods. The target group was created based on the Russian clinical guidelines; its number was calculated using Russian registry data. Based on the published results of the clinical trial of alirocumab ODYSSEY OUTCOMES in a group of patients with LDL cholesterol levels of more than 2.6 mmol/l (100 mg/dl), a model was built to estimate the number of fatal and non-fatal outcomes in the target group with standard therapy and with alirocumab.Results. The effect of alirocumab administration was modeled in patients of working age who had a myocardial infarction less than 12 months ago with an LDL cholesterol level of more than 5.0 mmol/l, the number of this group in the Russian Federation was estimated to be 3,029 people. It has been shown that with therapy in this group, mortality can be reduced by 29%, and the number of non-fatal cardiovascular events — by 22%, i. e. alirocumab therapy in this group for 2 years can prevent 29 deaths and 185 non-fatal events, with an increase in the duration of therapy to 5 years, the number of lives saved will be 117 and 401 non-fatal cardiovascular events will be prevented.Conclusion. Modeling has shown that alirocumab therapy in patients with recent myocardial infarction and LDL cholesterol levels above 5.0 mmol/L will significantly reduce mortality in this group and prevent the development of serious nonfatal cardiovascular complications, which will also reduce the burden on specialized hospitals, as well as prevent patients from becoming disabled. At the same time, decision making requires a balanced consideration of all ethical, clinical and economic aspects, including the assessment of costs and potential effects from the position of the of a willingness to pay and the formation of the budget of the health system

SOCIO-ECONOMIC DAMAGE BY ACUTE CORONARY SYNDROME IN RUSSIAN FEDERATION

Aim. To estimate the economic damage by acute coronary syndrome (ACS) in Russia in 2006-2009. Material and Methods. Direct costs and economic losses associated with ACS were estimated. The structure of direct costs includes the costs of hospitalization, medical emergencies, out-patient visits, high-tech medical care, as well as drug therapy in outpatient treatment. Losses in the economy associated with ACS include loss of gross domestic product due to death in working-age, temporary disability and payments of disability benefits. Estimation of economic damage by cardio-vascular diseases was based on analysis of Russian Ministry of Health official statistics. Results. Approximately 520,000 cases of ACS are registered annually (36,4% - myocardial infarction, 63,6% - unstable angina). Trend to increased mortality from myocardial infarction, especially among women, was found during the analyzed period. From 2000 to 2009 this index rose from 34.9 to 41.1 per 100,000 of population among women, and from 52.3 to 55.9 per 100,000 of population among men. Total direct costs of health care for patients with ACS in 2009 amounted to almost 21 billion rubles, and indirect – 53.5 billion rubles. The total economic damage by ACS in Russia in 2008-2009 exceeded 70 billion rubles per year. Conclusion. ACS in Russia is connected with significant social and economic damage. Most part of this damage is indirect losses in economy due to premature mortality of working aged men

Strategic Environmental Assessment and Monitoring of the Zaslavsky Reservoir

10995/27938В данной статье рассмотрено Заславское водохранилище и его влияние на окружающую среду, а также данные о стратегической экологической оценке и мониторинг данного водного объекта.This article examines the Zaslavskoye reservoir and its impact on the environment, as well as data on the strategic environmental assessment and monitoring of this water body

Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci for subtyping of mycobacterium tuberculosis Beijing isolates

Mycobacterium tuberculosis Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing

Microevolution of extensively drug-resistant tuberculosis in Russia.

Extensively drug-resistant (XDR) tuberculosis (TB), which is resistant to both first- and second-line antibiotics, is an escalating problem, particularly in the Russian Federation. Molecular fingerprinting of 2348 Mycobacterium tuberculosis isolates collected in Samara Oblast, Russia, revealed that 72%belonged to the Beijing lineage, a genotype associated with enhanced acquisition of drug resistance and increased virulence. Whole-genome sequencing of 34 Samaran isolates, plus 25 isolates representing global M. tuberculosis complex diversity, revealed that Beijing isolates originating in Eastern Europe formed a monophyletic group. Homoplasic polymorphisms within this clade were almost invariably associated with antibiotic resistance, indicating that the evolution of this population is primarily driven by drug therapy. Resistance genotypes showed a strong correlation with drug susceptibility phenotypes. A novel homoplasic mutation in rpoC, found only in isolates carrying a common rpoB rifampicin-resistance mutation, may play a role in fitness compensation. Most multidrug-resistant (MDR) isolates also had mutations in the promoter of a virulence gene, eis, which increase its expression and confer kanamycin resistance. Kanamycin therapy may thus select for mutants with increased virulence, helping preserve bacterial fitness and promoting transmission of drug-resistant TB strains. The East European clade was dominated by two MDR clusters, each disseminated across Samara. Polymorphisms conferring fluoroquinolone resistance were independently acquired multiple times within each cluster, indicating that XDR TB is currently not widely transmitted. © 2012 by Cold Spring Harbor Laboratory Press

Mother-fetus immunogenetic dialogue as a factor of progeny immune system development

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers during in vitro fertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status

An association between type A porcine endogenous retrovirus copy number and hematological parameters and gender in miniature pigs

Pig is the most promising species for transplantation of organs and cells into humans, although implementation of xenotransplantation in clinical practice has been hindered by the risk of infecting the recipient with zoonotic infectious diseases. Porcine endogenous retroviruses (PERV) are capable of incorporating copies of DNA into the genome of a host cell. Based on the nucleotide sequence of the envelope gene (env), three main types of pig retrovirus, PERV-A, PERV-B and PERV-C, have been recognized, with PERV-A and PERV-B having the capability of infecting human cell lines in vitro. Selection for animals with low copy number of retroviruses in the genome using simple phenotypic indications is required for the widespread implementation of xenotransplantation. The objective of this study was to evaluate the correlation between PERV-A env gene copy number and hematological parameters, gender and coat  color in miniature pigs of the Institute of Cytology and Genetics (ICG) SB RAS. Reference values for eighteen blood parameters of miniature pigs were determined, including white blood cell count (WBC), red blood cell count (RBC), platelet count (PLT), absolute (LYM#) and relative (LYM%)  lymphocyte counts, absolute (MID#) and relative (MID%) monocyte, basophil and eosinophil counts, absolute (GRA#) and relative (GRA%) granulocyte counts, hematocrit (HCT) and thrombocrit (PCT), mean cell volume (MCV) and mean platelet volume (MPV). Males had significantly higher reference values for WBC, MID#, GRA# and red cell distribution width (RDW-CV) as compared to females. The mean corpuscular hemoglobin  concentration (MCHC) and platelet distribution width (PDW-CV) were significantly higher in female animals. No correlation between PERV-A env gene copy number and the coat color of  animals was detected, suggesting that retroviral insertion sites and genes that determine the coat color of miniature pigs, namely KIT (chromosome 8) and MC1R (chromosome 6), are either located far apart on same chromosome or on different chromosomes. The copy number of PERV-A env gene in males was lower than in females. Presence of multiple copies of PERV-A on the X-chromosome is the most probable cause of such gender-related differences in miniature pigs. Thus, male miniature pigs of ICG SB RAS should be the source of material for xenotransplantation

Morphophysiological alterations caused by insertional mutagenesis of contactin 5 (Cntn5) gene in transgenic mice

Transgenesis has become a routine for modern biological studies. The most popular method for producing transgenic animals–pronuclear microinjection–frequently leads to host gene disruption due to a random transgene integration. In this paper, we report our analysis of morphophysiological parameters of the transgenic mouse line GM9, in which a transgene designed for milk-specific expression of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene was integrated into the intron of the Contactin 5 gene (Cntn5). We studied Cntn5 expression with RT-PCR and discovered that its expression in the brain, the primary organ of Cntn5 activity, was unperturbed. However, transgenic animals had less Cntn5 transcripts in other tissues such as the kidney and heart. In addition, we observed a decreased amount of splice variants of Cntn5 exons that flank the transgene integration site. These data suggest that the transgene integration event might affect proper Cntn5 splicing in some tissues. Publications exist that imply that some polymorphisms in the Cntn5 gene are associated with obesity and arterial hypertension in humans. We evaluated core parameters of lipid metabolism and heart activity in mice homozygous and heterozygous for Cntn5 mutation using wild- type animals as control. Our results uncovered that homozygous mutant mice have lower body weight than controls and that it is caused by slower accumulation of fat tissue. Cntn5 mutants also exhibit abnormalities in blood circulation: homozygous Cntn5 mutants are characterized by a higher blood pressure and heart beat rate, as well as faster blood flow in the tail vessels. Heterozygous animals showed intermediate results for all of these parameters

Metabolic and motor activity effects of microalgae (Chlorella vulgaris) in laboratory mice

In recent years, the microalgae (Chlorella vulgaris) have increasingly attracted great interest as a potential source of pharmacologically active compounds. Showing anticoagulation, antioxidant and antitumor activities of Chlorella revealed its hypotensive properties. The aim of this study was to evaluate the effects of Chlorella suspension on the weight of the animals, their moving activity, and erythropoiesis. The study was performed on males and females of ICR mice. The animals from the experimental group drank only the Chlorella suspension during 3 weeks and were given standard food. Control animals drank during this period only water and had the same food. The body weight of males in the control and the experimental group with Chlorella did not change, while females in the experimental group showed an increase of body weight in a week. A similar pattern was obtained for estimation of animal body weight changes relative to food consumption. The number of red blood cells in females and males from group with Chlorella increased only after 3 weeks after the start of the experiment. Hemoglobin also increased only after 3 weeks after the start of Chlorella consumption, but only for females. All groups of animals had the same motor activity during experiment. Blood sampling resulted in a reduction of activity in control males and females as well as in males with Chlorella. The motor activity of females with Chlorella after blood sampling did not change. So, consumption of the Chlorella suspension by females leads to more effective digestion and resulted in increased body weight, improved erythropoiesis resulted in increased red blood cells and hemoglobin and also increased their resistance to acute stress. The males in the same situation increased only the erythropoiesis