Search

Background. Molecular structures combining a phosphorus-containing counterpart and non-polar radicals are employed in design of pro-drugs as structural and functional groups necessary for transportation of drugs through cellular barriers. It is assumed that the carrier itself does not exhibit biological activity. However, the “organic phosphate – alkyl radical” complex may possess its own metabolic and pharmacological properties even in the absence of a drug moiety.The aim. To study the effect of fluorinated alkyl phosphates on the growth of bacterial test cultures in an agar medium and to identify conjugated metabolic markers using UV/visible spectroscopy.Materials and methods. The effect of six organyl phosphates on the growth of five types of bacteria under aerobic conditions was evaluated by the method of wells in an agar medium. For solutions containing cell metabolites of Pseudomonas aeruginosa, the absorption spectra were recorded at 250–280 nm. The principal component analysis (PCA) was used for multivariate comparative analysis of the spectra. Results. The studied organyl phosphates bearing the ethyl and propyl radicals are potential temporary carriers of the drug moiety, since they are capable of penetrating through cellular barriers. However, the fluorinated compounds exhibit bactericidal properties, the degree of which depends on the arrangement of fluorine atoms in the radical. The most active compounds are those exhaustively halogenated at the terminal carbon atom of the ethyl radical (-СН2-СF3), while non-fluorinated organyl phosphate is the least active. UV/visible spectra of P. aeruginosa cultivation products, according to PCA data, contain patterns reflecting the metabolic effects mediated by these structural features of the radicals.Conclusion. In terms of practical application of the studied compounds, the activity of a proantibiotic based on organyl phosphate with a non-fluorinated ethyl(propyl) radical will be determined only by the specificity of the drug moiety. Exactly the same molecule, but exhaustively fluorinated at the terminal carbon atom of the alkyl radical, is likely to be characterized by lower specificity and higher activity under the additive (or synergistic) action of metabolically active groups.

Aim. To evaluate the level of circulating free nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in hypertensive patients with high cardiovascular risk.Material and methods. The study included 70 patients, of which 51 were patients with hypertension (HTN) and 19 were healthy. The study of the level of circulating free nDNA and mtDNA was carried out using quantitative polymerase chain reaction (PCR). Additionally, demographic data, comorbidities, risk factors, heredity, results of complete blood count and biochemical blood tests, electrocardiography and echocardiography were analyzed.Results. The level of nDNA in HN patients was significantly higher than in healthy patients: Me (LQ; UQ) — 227 (110; 370) copies/mL and 88 (62; 116) copies/ml, respectively (p

Aim. To study the associations of allelic variants of the CYP2C19 gene with atherosclerotic lesions of the coronary arteries in patients with acute coronary syndrome (ACS) in the North of Siberia (Surgut) and in large cities of the Siberian Federal Okrug (SFO).Material and methods. During the study 296 patients with ACS were examined at admission to cardiology hospitals in large cities of the North (Surgut, 114 patients) and SFO (Irkutsk and Kemerovo, 182 patients). All patients underwent coronary angiography and genetic research (identification of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles).Results. In patients with ACS living in the North of Russia allelic variant CYP2C19*17 (*17/*17) is positively associated with the severity of lesion of left coronary artery (LCA) (χ2=9,81; p=0,002), as well as with at least 50% stenosis, more than 70% lesion of the proximal or middle part of the three main arteries, or more than 50% lesion of LCA trunk (χ2 =6,52; p=0,011), and previous myocardial infarction (χ2=8,15; p=0,004). Among patients with ACS living in cities of the Siberian Federal Okrug, the allelic variant CYP2C19*17 (*17/*17) is directly associated with diabetes mellitus (χ2=5,48; p=0,019) and less than 45% left ventricular ejection fraction (χ2=4,20; p=0,040). Regression analysis showed that in patients with ACS living in the northern region of Russia, only the allelic variant CYP2C19*17 (*17/*17) correlated with at least 50% stenosis of LCA trunk (Exp (B): 11,623, 95% CI: 1,893; 71,342; p=0,008). It did not correlate with the male sex, age, smoking and diabetes (p>0,05).Conclusion. The results show the presence of direct associations of CYP2C19*17 alleles with prognostically unfavorable coronary atherosclerosis in ACS patients living in the North of Siberia.

The narrowing of the lumen of the trachea due to cicatricial stenoses of the trachea is one of the urgent problems of the modern surgery. The processes taking place in the trachea and lungs lead to a change in the state of the immune system. Assessment of the dynamics of indices of nonspecific resistance is one of the methods for assessing the severity of the course of the disease. We studied the indices of nonspecific resistance of the organism in narrowing the lumen of the trachea in an experiment in the early postoperative period. The study was carried out on the basis of the scientific department of experimental surgery with the vivarium of Irkutsk Scientific Centre of Surgery and Traumatology, on 24 white male Wistar rats with a body weight of 300–350 g. We simulated narrowing the lumen of the trachea by placing a silicone tube in the lumen of the trachea for 14 days. The parameters of phagocytosis, the state of phagocytic activity of blood neutrophils, spontaneous NBT-test, induced NBT- test were studied. The animals were withdrawn from the experiment on the 3rd, 7th and 14th day. We revealed that as a result of narrowing of the lumen of the trachea with the original procedure, the nonspecific resistance of the organism was violated with inhibition of the phagocytic activity of leukocytes. There was inhibition of phagocytic activity of leukocytes and depletion of the functional reserve of leukocytes.

Clopidogrel remains the main antiplatelet therapy drug for patients after coronary stenting (CS) due to acute coronary syndrome (ACS). The paper contains substantiation and design of an observatory study with the purpose to test the hypothesis that high frequency of of cytochrome CYP2d9*2 polymorphism is associated with coronary stent thrombosis and with paradoxical response to clopidogrel in Siberian residents after CS due to ACS. Response to clopidogrel will be registered by means of light transmission aggregometry (turbidity method) in presence of adenosine diphosphate. Over the period of 30 days after coronary stenting, patients receiving clopidogrel will undergo 4 visits to assess antiplatelet therapy efficacy (end point - early stent thrombosis) and safety (all bleeding events), with consideration of genetic profile. Ethic support of the study

Purpose: to study associations of homozygous allelic variants of VEGFR2*C/*C and CYP2C19*17/*17 genes with atherosclerotic lesion of coronary arteries in patients with acute coronary syndrome (ACS) in the North (Surgut) and in large cities of the Siberian Federal District of Russia (Irkutsk and Kemerovo). 257 consecutive patients with ACS upon admission to the cardiological hospitals of Surgut, Irkutsk and Kemerovo has been included in the study. All examined patients underwent coronarography and determination of allelic variants of VEGFR2*C/*C and CYP2C19*17 /*17 genes. In patients from Surgut has been determened the direct associations of the combination of allelic variants of VEGFR2*C/*C + CYP2C19*17/*17 with indicators of severe coronary atherosclerosis (lesion of the left coronary artery trunk (LCA), LCA stenosis more than 50 %, proximal or medial lesion of the three major arteries more than 70 % (PLA) and the presence of PLA or stenosis of the LCA trunk more than 50 %). Such associations were not found in patients from Kemerovo and Irkutsk. The multivariate analysis determined the direct effect of combination of allelic variants of the VEGFR2*C/*C and CYP2C19*17/*17 genes on the presence of PTA or stenosis of the LCA trunk more than 50 % in patients with ACS from Surgut regardless of males gender, ages and smoking (Exp B) = 21.065, 95 % CI (2.003; 221.524), p = 0.011). Thus, the combination of allelic variants of VEGFR2*C/*C and CYP2C19*17/*17 genes directly affects the presence of severe coronary atherosclerosis in patients with ACS from Surgut.

Clinical drug trials in Irkutsk Scientific Center of Surgery and Traumatology began in 2005. In 2013, the laboratory of clinical trials was established in the science department of clinical surgery. We analyzed the experience of Irkutsk Scientific Center of Surgery and Traumatology in international multicentre trials. Participation in international multicentre trials allows the Irkutsk Scientific Center of Surgery and Traumatology to get affiliated with the publications in first quartile scientific journals. The experience of the laboratory in clinical trials is projected into practical work of other institutes - Hospital of Irkutsk Scientific Center SB RAS and Irkutsk Regional Clinical Hospital. The important objectives of the laboratory of clinical trials are developing the protocols, performing drug clinical trials and medical device clinical trials. The laboratory carries out admission of patients for observational trial PROTOCOL. One of the fields of work of the laboratory is the prospect of clinical testing of developed clinical technologies.

Genetics of arterial hypertension is broadly discussed as of one of multifactorial diseases. Invention of an algoritm for risk stratification based upon genetic parameters, gives chance to select groups of higher essential hypertension (EH) risk with the aim of primary prevention. One of such prototypes was assessed, that inculdes 11 genetic markers, in 30 patients with known clinical parameters; 19 of those were with EH and 11 normotonics. Individual impact is assessed of each marker and comparison done for total risk in patients. As a result, there were no differences found in individual risk for patients with and without EH by 11 markers, between subgroups. There was protective effect found for the allele С rs1799998 of gene CYP11B2 (OR 0,247; CI=[0,081-0,754], p=0,01).

We studied capabilities of confocal laser scanning microscopy in the analysis of lipid droplets volume and of quantity of functional mitochondria and reactive oxygen species production in liver cells for early diagnosis of cytochemical disturbances at dyslipoproteinemia (16 days of experiment). The results showed the increase of lipid droplets volume in hepatocytes, decrease of functional mitochondria and increase of reactive oxygen species production. We evaluated the potential of real-time PCR method in the analysis of mitochondrial DNA of blood plasma at early stages of dyslipoproteinemia and in experimental infarction. On the background of registered blood lipid metabolism disorders and structural and functional changes in liver cells, we determined the tendency to three-time increase in concentration of circulating cell-free mtDNA on the 16th day of dyslipoproteinemia as compared to the control data. We used a model of myocardial infarction to show statistically significant increase in the level of circulating cell-free blood mtDNA from 48 hours after adrenaline injection and we found that this level maintained up to 144 hours after adrenaline injection. Obtained data can serve as a basis for creation of technologies for diagnostic monitoring of atherosclerosis and myocardial infarction severity.

HGF is one of the factors taking part in regeneration and recovery of liver after injury. The article is dedicated to the study of influence of single HGF intake on the indices of non-specific immune response in rats after 70% liver resection in the early postoperative period. Research was conducted on 42 six-months white male Wistar rats of 250-300 g. It was revealed that level of segmentonuclear neutrophils and lymphocytes in the group with HGF intake stand at normal level on the 2nd day and normalizes to the 11th day that testifies to the decrease of inflammatory response. Increased level of leukocytes and monocytes is registered in the group with HGF intake. Also integrity of non-specific resistance in the early postoperative period on the 2nd day is registered. Suppression of phagocytosis indices with preservation of functional activity of phagocytes was registered to the 11th day.

Aim. To reveal the association of gene polymorphism CYP2С19*2 and recurrent early stent thrombosis in coronary vessels, and paradoxal response to clopidogrel intake in patients — the inhabitants of Siberian Region — after acute coronary syndrome.Material and methods. Totally 105 patients studied, hospitalized for stenting of coronary arteries in acute coronary syndrome, never received clopidogrel previously. The polymorphism of studied СУР2С19: *2, *3, *17 alleles, as assessment of platelet aggregation with ADP before and after clopidogrel intake, as of endpoints on safety and efficacy during 30 days (thrombotic complications, bleeding).Results. Within the selected patients there was no any significant association of any CYP2С19*2 and/or CYP2С19*3 alleles and paradoxic laboratory reaction. There was significant association of the CYP2C19*17 gene carriage and bleedings. When comparing the groups of patients having or not having complications related to clopidogrel (thrombotic or bleedings), there was significant difference in residual platelet aggregation.Conclusion. The results of the study might be strongly significant for the decisions making on double antiplatelet therapy and on the tactics of drugs preference.

The aim of research: the studying of blood lipid spectrum, C-reactive protein concentration, and free circulating mitochondrial DNA changes in the course of aorta atherosclerosis development in early steps of high-cholesterol diet in experiment. Material and methods. Dyslipidemia was induced by high-cholesterol diet in rabbits “Chinchilla”. The C-reactive protein level and lipid spectrum was analyzed with Beckman synhron 4 multianalyzer (Beckman coulter, USA). The mitochondrial DNA level was registered by real-time PCR. The ultra structure of aorta surface was studied by scanning electron microscopy. Results. It was shown that in the blood of experimental animals is formed the Beckman imbalance of atherogenic and antiatherogenic cholesterol fractions (on 2 days of dyslipidemia) and iselevated the C-reactive protein level (on the 8 days). Concurrently, on the 16 days of study, we registered the leucocyte adhesion on the aorta surface in the areas of connections with arteria, which could be focuses of atherosclerotic plaque development. The level of free circulating mitochondrial DNA showed the tendency to 3-fold elevation in comparing with control. However, this data predetermined the prospects of blood plasma mitochondrial DNA level studying on the more late stages of dyslipidemia. Conclusion. In the whole, the detected complex of biochemical disturbances of blood and ultrastructural changes of aorta surface in the course of early steps of high-cholesterol diet maybe prospective model of early events of atherosclerosis for pre-clinical translational research in the development of new technologies for diagnostics, prophylaxis, and treatment of lipid metabolism disturbances and atherosclerosis.

The review concerns on the data about ED in CVD pathogenesis as the leading cause of death. The morphofunctional characteristic of endothelium is discussed, its synthetic activity and regulators. Also the regulatory role of NO-synthase and its gene polymorphism, as their clinical significance as the ED development factors. Also the vasodilator and vasoconstrictor balancing mechanisms of ET, showing different functions. Polymorphism of genes influences ET-1 activity, that has significant value for RAAS regulation with ACE and the influence of rare polymorphisms in CHD risk, MI, diabetic nephropathy. Pathogenetic significance of ED in the conditions of oxidative stress defines clinicists attention onthis pathology, related to atherosclerosis, and molecular and genetic aspects of CHD formation do dictate inevitability of personalized medicine for prognosis and prevention, as pharmacogenomics – for endothelial pathology correction of cardiovascular system in general.

The article presents the analysis of the inventive work of the Institute of Traumatology and Orthopaedics being a part of the Scientific Center of Reconstructive and Restorative Surgery SB RAMS. Main directions of patent work including hip replacement technologies, diagnostics and treatment of spine and spinal cord pathologies, methods of managing bone tissue regeneration and of using autologous tissues for osteoplasty, septic osteology, anesthetic management techniques in orthopedic surgery and also of evaluation and modulation of functional state of organism were marked. The effectiveness of patented technologies is proved in the current researches of the Center that allows to transmit them into practical health care.

The article presents the review of inventive and patent work of employees of Scientific Center of Reconstructive and Restorative Surgery SB RAMS from the foundation of institute of surgery till nowadays. Main areas of researches (in the form of patents) are determined: prevention and treatment of surgical infection, methods of treatment of actual surgical pathology of neck, chest, abdomen and soft tissues and also instrumental and laboratory diagnostics of these conditions. The models of pathological processes developed in experiment and cell technologies are patented. The level of patent defense of researches is considered to be corresponding.

The aim of the present study is to analyze the dynamics of free circulating mtDNA level in blood after occlusion of the upper one-third left descending branch of the coronary artery. We showed that the concentration of free circulating mtDNA of blood tends to decrease 24 hours after ligation; it increased and reached values close to control samples 48 and 72 hours after ligation. These data define the need in further investigation of the dynamics of this parameter during later periods of myocardial infarction modeling that will contribute to objective evaluation of its significance for acute myocardial damage diagnostics and prognosis.

The article is devoted to the estimation of morphological changes in liver of experimental animals with acute hepatic failure caused by toxic injury of liver under the influence of xenotransplantation of culture of cryopreserved cells of liver and isolated cryopreserved neonatal hepatocytes. It was determined that undamaged hepatocytes with simultaneous decrease of number of vacuolated cells, preservation. of beam structure, decrease of fat insertions prevailed in the liver of animals with xenotransplantation of culture of cryopreserved cells of liver to the 6th day. At the transplantation of isolated neonatal hepatocytes number of hepatocytes with undamaged structure decreased and number of damaged hepatocytes increased. Thus, cultivated cryopreserved cells of liver are the cells of choice of correction of acute toxic liver injury.

Prevention of deep vein thrombosis and pulmonary artery thromboembolism using heparin is a gold standard in orthopedics. The aims of the work were to evaluate and to compare efficiency and. safety of thromboprophylaxis in orthopedics using Pradaxa and Clexane in long-term follow-up. 96 patients are included in research. Follow-up information on all patients was collected either through telephone contact with the patients or by questionnaire. Conclusions: The number of respondents appeared insufficient for the actual check of an initial hypothesis. In modeling outcomes plausibility of a hypothesis isn't disproved. Recommendations about VTE prevention after discharge in our study are differed from the accepted standards.