Intermediate results 2016 of a search study of translational diagnostic methods Mitochondrial dysfunction in patients with chronic myocardial ischemia and/or head Brain

Purpose of the study. To rate prognostic properties of changes in mitochondrial DNA concentration in the blood plasma of patients with chronic cerebral ischemia and ischemic heart disease in relation to the disease and the effectiveness of the therapy. Materials and methods. The study involved patients suffering from coronary heart disease (CHD) and chronic cerebral ischemia (CCI) with stable and unstable atherosclerotic plaques, who have signed informed consent to the data processing within the framework of scientific research. The patients were admitted to the hospital for examination and treatment of CHD and CCI in Cardiology and Neurology Unit of the Hospital of ISC SB RAS. The subjects underwent laboratory and instrumental examination and analysis of the level of free circulating serum mitochondrial DNA by real-time PCR (copies/ml). The examination results considered as satisfactory were compared with the mtDNA levels before and after the treatment. Results. The average value of the mtDNA levels before and after the treatment in patients of neurological and cardiological profile were significantly different: 1 093 686 copies/ml vs 418 046 copies/ml, respectively (p = 0.02). Unlike women, men mtDNA levels statistically significantly (p = 0.03) decreased after the treatment. We revealed statistically significant differences in mtDNA level indicators before and after the treatment, depending on the definition of the series (p = 0.0010) for rank test Kruskal – Wallis test. The results of the proposed research will help to identify prognostic factors of destabilization of cell damage and plaques in endothelial dysfunction, atherosclerosis and its complications, to conduct clinical test of the method for predicting and diagnostics of cellular damage in chronic ischemia on a background of atherosclerosis.

Modeling of pathological processes in the experiment-the first step in translational medicine

The paper discusses the significance of animal experiments and modeling of pathological processes for pre-clinical drug trials, methods of diagnostics and treatment, which correspond to the concept of the first phase of the study in translational medicine. The article provides information on the methodology, legal framework and applications of experimental surgery. The simulation results of dyslipidemia and hypoparathyroidism are given. Simulation of pathology in small laboratory animals is regarded as an integral component of basic and applied biomedical research.

Advantages of a personalized approach to the prevention and treatment of cardiovascular diseases in the staff of the INC Of the SBRAS

Purpose of the study. To test the functional associations of polymorphic variants of genes in the regulation of blood pressure and vascular tone in employees of the ISC SB RAS. Materials and methods. The study involved patients, employees of the ISC SB RAS, being under care of the outpatient clinic of the Hospital of the ISC SB RAS. During routine laboratory testing the patients were taken 2 ml of blood for genetic analysis and further molecular genetic study on “Hypertension”, “Endothelial dysfunction”, “Pharmacogenetics”, “Inflammatory response” panels. Results. In the analysis of 12 genes coding for key proteins of hormonal enzyme blood pressure regulation systems, polymorphism of CYP11B2 showed statistically significant correlation with the presence of arterial hypertension, which makes its further study promising. The presence of allele C showed protective significance in relation to the development of hypertension with OR = 0,247. When checking associations of functional polymorphic variants of genes, the products of which are involved in the regulation of vascular tone, with hypertension in patients younger than 50 years old we found association of T/T rs5443GNB3 genotype with the debut of hypertensive disease under the age of 50. The data obtained allow the doctor to choose the most personalized and effective safe drug from certain groups, as well as its dose for employees having passed molecular genetic testing. These data can reveal predisposition to the most widespread and socially significant diseases in the surveyed subjects and provide specific personalized recommendations for the prevention of these diseases.

Department of Biomedical Research and Technologies of the Irkutsk Scientific Center of the SBRA Sprerequisites for the creation and direction of work from the editor

The article presents the analysis of depopulation processes of the Russian Federation on the example of the Irkutsk region. The author evaluates the strategy of the health care system in Russia in solution of depopulation problems. Types and features of depopulation process in Russia are established. The situation of demographic processes in the Irkutsk region is described. The region is considered, as the analysis has shown, to be a typical model of depopulation processes in Russia. The paper presents the analysis of present-day measures taken for the development of health care system. It is revealed that without regard to the state and mechanisms of public health functioning, the effectiveness of presented measures on improvement of health care system is limited.

The results of fundamental and translational research carried out In the Department of Biomedical Research and Technology of the SBRAS INC in 2012-2016

The results of basic and translational research of the Department of Biomedical Research and Technology of Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences in 2012–2016 The paper presents the results of interdisciplinary research carried out in 2012–2016. The review includes the study of molecular mechanisms of pathogenesis of reparative regeneration, experimental substantiation of methods of diagnosis and prognosis of systemic disturbances of regeneration process, carrying out clinical trials of medicinal products and the formation of observational studies in the field of personalized medicine, the preparation of practical recommendations on the testing of previously developed surgical methods of prevention or correction of postoperative recovery disorders. New data are obtained on the role of the MAP-kinase cascade in the process of regeneration of muscle tissue. It has been established, that with a significant increase of VEGF concentration at the site of the repair of ischemic myocardium, progenitor cells with the CD34+CD45+ phenotype appear, which opens up prospects for the development of biotechnology to restore the damaged myocardium with its own pool of progenitor cells. The new data on the role of growth factors in the post-infarction remodeling are found. It has been revealed, that in local increase of selenium concentration low intensity of mineralization of forming callus in the area of the damage is observed and the formation of bone regeneration slows down. Prospects for the use of nanocomposites of elemental selenium for modulation of reparative response are marked. The dynamics of the level of free circulating mitochondrial DNA (mtDNA) of blood in the early stages of experimental dyslipidemia has been studied. Atherogenic blood factors do not have a significant effect on the release of the mtDNA from dyslipidemia target cells. On the model of acute small-focal myocardial ischemia, we revealed the increase in the mtDNA levels. Prospects of broadcast of diagnostic mtDNA monitoring technology in myocardial ischemia have been marked. The mtDNA monitoring was first tested as a molecular risk pattern in acute coronary syndrome. In survived patients, the concentration of freely circulating mtDNA in blood plasma was 164 times lower. The probability of death of the patient with a high level of mtDNA (over 4000 copies/mL) was 50 % (logit analysis). Methodological level of translational research in the ISC SB RAS has increased due to effective participation in international multi-center clinical trials of drugs, mainly direct anticoagulants: fondaparinux, edoksabana, betriksabana. “Feedback broadcast” of the results of clinical trials of p38-kinase inhibitor, was carried out in the process of changing the model (initially – neuropathic pain) for coronary atherosclerosis. Technologies of pharmacogenetic testing and personalized treatment of diseases in the employees of the Irkutsk Scientific Center were applied. Step T2. Previously developed at the Irkutsk State Medical University and the Irkutsk Scientific Center of Surgery and Traumatologies approaches to surgical prevention and medicinal correction of postoperative hyposplenism were translated into practical health care. Thus, these results obtained in different areas of translational medicine will determine scientific topics of the department in future research cycle.

Department of Biomedical Research and Technologies of the Irkutsk Scientific Center of the SBRA Sprerequisites for the creation and direction of work (editorial)

The history of creation and the main aspects of work of the Department of Biomedical Research and Technology of the Irkutsk Scientific Center for the first 5 years is described. Selected as a methodological framework, the concept of translational medicine has provided, on the one hand, a wide range of research, on the other hand it brought the fundamental research to clinical testing on the basis of Hospital of the Irkutsk Scientific Center of the SB RAS. The materials included in the presented collection were announced.

The development of original methodologies of directed synthesis of le-Carbs their analogs and precursors base donacetylene and its derivatives

New reactions, which have been discovered and continue to be developed in A.E. Favorsky Irkutsk institute of chemistry SB RAS on the basis of acetylene, a product of oil, gas and coal processing and multi-faceted building block for organic synthesis, have been considered. These reactions provide for the shortest routes to construction of fundamental heterocyclic scaffolds (pyrroles, imidazoles, pyrazoles, indoles, pyridines, dihydropyridines, etc.) with desirable and optimum combination of functional pharmacophoric groups and fragments, which are responsible for antiviral (HIV, flu), antitumor, tuberculostatic and hypotensive activities.

Association of polymorphisms Gene CYP2C19 with endpoints of efficacy and safety of clopidogrel therapy And platelet aggregation in patients with acutecoronary syndrome study Protocol

Aim: to reveal the association of gene CYP2C19 polymorphisms and efficacy and safety endpoints of clopidogrel therapy in patients with acute coronary syndrome. Materials and methods. A total of 431 patients with acute coronary syndrome undergoing coronary stent placement was studied. CYP2C19 polymorphisms (*2, *3, *17) were evaluated, platelet aggregation with ADP and efficacy and safety for 30 days after coronary stent placement was studied. Results. Within the selected patients there was no significant association between carriage of at least one allele of the CYP2C19*2, and/or CYP2C19*3 and paradoxical response to clopidogrel. Significant association between carriage of allele CYP2C19*17 and the presence of bleeding was detected. The algorithm for selection of individual drug therapy for patients receiving clopidogrel therapy was developed. Conclusion. The results can be extremely important for decision-making about the strategy of dual antiplatelet therapy and the tactics of choice of drugs.