Home – Home – Jornals – Siberian Scientific Medical Journal 2018 number 6

The aim of the study is to perform an immunohistochemical analysis of the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) in the myocardium of Wistar rats in doxorubicin-induced cardiomyopathy and the administration of betulonic acid amide as an agent with a polytarget effect in comparison with the severity of destructive processes in heart muscle cells. Material and methods. Wistar male rats (total 51 animals) were used in the work with isolated and combined administration of a single sublethal dose of doxorubicin (7 mg/kg) and course administration of betulonic acid amide at doses of 50 mg/kg/day and 100 mg/kg/day for 3 and 14 days. Immunohistochemical evaluation of VEGFR2 expression in the myocardium was carried out with the calculation of the index of VEGFR2-positive cardiomyocytes; the volume density of cardiomyocytes with lytic changes was estimated using stereological analysis. Results and discussion. A single administration of doxorubicin (at a dose of 7 mg/kg) caused destructive changes in cardiomyocytes and hemodynamic disorders in myocardium, which increased with the duration of the experiment (14 days). The complex of the revealed structural and metabolic lesions reflected the development of regenerative-plastic insufficiency of cardiomyocytes, which is the basis of cardiac insufficiency in anthracycline cardiomyopathy. Morphological changes in the myocardium with isolated administration of betulonic acid amide were largely determined by the dose used. At a dose of 100 mg/kg, myocardial changes were similar in severity with doxorubicin-induced changes. Combined use of doxorubicin and betulonic acid amide revealed the most significant structural damage of the myocardium. It was shown that the increase in the volume density of lytic altered cardiomyocytes correlated with a significant increase in VEGFR2 expression (correlation coefficient varied from 0.620 to 0.980).

The catalytic domain of the nuclear inclusion protein of the tobacco etch virus protease, TEVp, is used for the cleavage of artificial fusion polypeptides. However, the production of a recombinant enzyme has certain difficulties, such as a low yield of the product and its low solubility in physiological solutions. The aim of the study was to optimize the methods of producing a recombinant enzyme TEVp from E. coli producing cells. Material and methods. The studies were carried out on E. coli cells st. BL21 (DE3). The enzyme was synthesized by cells in the form of a fusion polypeptide with maltose-binding protein (MBP), followed by self-cleavage. Biomass production was carried out under various conditions: a change in the temperature regime, the time of incubation of cells with an inducer, the concentration of the inducer and the growth phase of the culture with the addition of an inducer. The enzyme was isolated under native conditions and with an increased concentration of sodium chloride by affinity chromatography. The enzyme activity was tested on chimeric recombinant human apolipoprotein A-I (~33.4 kDa). Results and discussion. The results of the study showed that a significant influence on the final yield of the enzyme was provided by the growth phase of the culture when the inducer was added. Optimal conditions for obtaining biomass were found as follows: incubation temperature with an inducer 30 °C; incubation time 4 hours; inducer concentration 200 μM; optical density with inducer addition 2.0-2.5 optical units per ml. Sodium chloride concentration in the buffer solution during isolation of the protein was 150 mM. The yield of the enzyme under these conditions reached 50 mg from a liter of cell culture. A similar yield of the enzyme was obtained using the method of auto-induction of cell culture. In all cases, enzymes retained their activity. Conclusion. It was shown that the greatest influence on the yield of the recombinant enzyme from E. coli producing cells strain BL21 (DE3) in the expression vector pD441-MBP under the regulation of the bacteriophage promoter gene «T5» was exerted by the growth phase of the cell culture at the time of gene expression launch.

The article deals with the interaction of fluid flow in the «blood capillary - tissue - lymphatic capillary» system. On the one hand, the mutual influence of the components involved in the system is an important basis for maintaining homeostasis from the point of view of physiologically occurring processes, and changes in their structural and functional properties can be a triggering factor for impaired fluid balance, the appearance and development of a number of pathological processes, syndromes and diseases. The paper presents a mathematical model of metabolic processes that occur at the microcirculatory level and include the following interrelated processes: blood flow in the capillaries, fluid movement in the interstitium, metabolism between interstitial fluid and tissue cells, drainage into lymphatic capillaries. An approach is used to take into account the mutual influence of blood flow in the blood capillary and interstitial fluid in the tissue. The analysis of the solution results is carried out, the effect of various microcirculation parameters on the intensity of metabolic processes is investigated, and the most significant parameters are identified.

The purpose of the research was to detect structural alterations of the mesenteric lymph node of male rats-adolescents taking into account changes in the mineral metabolism against a background of chronic intoxication with lead acetate. Material and methods. The experiment was carried out on 4-week male adolescents Wistar rats (10 rats) receiving per os lead acetate solution at a daily dose of 10 mg / kg body weight for 21 days, animals of the control group (10 rats) received food without heavy metal. The mesenteric lymph node and liver were examined (staining with hematoxylin and eosin, azur II and eosin) by light microscopy and morphometry; bioelement content in the liver was determined using atomic emission spectrometry with inductively coupled argon plasma. The non-parametric Mann - Whitney U criterion and the Pearson criterion χ² were used as statistical methods Results and discussion. The lymph node changed from an intermediate (in control) into a fragmented functional type that promotes active lymph flow through the sine system of the lymphoid organ. The ratio of T-dependent functional zones of the lymph node decreases. The increase in lead concentration in liver tissues was detected in 100 % of the observations. In 60 % of liver samples, a decrease in the content of potassium and zinc was detected. In 40% cases there was manganese exchange disorder, in 20 % there were deviations in calcium, iodine, phosphorus and silicon amounts. Thus, the chronic effect of lead acetate subacute doses on the body of rat male adolescents results in pronounced shifts in the exchange of bioelements. Against the background of altered biochemical processes, structural and functional rearrangements are formed in the mesenteric lymph node: depression of the immune processing of lymph, activation of the transport function of the organ.

With the widespread development of the phenomenon of RNA interference, currently, researchers are puzzled to obtain effective carriers of small interfering RNA (siRNA). Previously, we obtained a modified recombinant polypeptide based on human apolipoprotein A-1 (apoA-I), capable of binding to plasmid DNA. The aim of the investigation was to study the possibilities of modified recombinant proteins of apolipoprotein A-I to transfer siRNA into tumor cells. Material and methods. The studies were performed on a model of transformed macrophages of mice RAW 264.7 that stably expressed the green fluorescent protein (GFP) gene (line of clone 8A3). Recombinant pro-apo A-I, its modified analog, carrying at the C-terminus of 10 amino acid residues of lysine (apo AK10), and Lipofectamine 2000 transfection reagent were studied as siRNA carriers. Proteins were obtained from the corresponding E. coli producer strains. The transfer object was a siRNA duplex, in which one nucleotide was complementary to the matrix RNA of GFP gene. Cell fluorescence was measured on the second day using a fluorescent plate analyzer. Results and discussion. The results of the study showed that proteins pro-apoA and apoAK10 labeled with fluorescein isothiocyanate penetrate the RAW 264.7 cells. The results of the study RNA interference showed that the incubation of cells with a mixture of miRNA and Lipofectamine 2000 caused a decrease in the fluorescence of the 8A3 cell lines, which indicates a correct selection of siRNA to the matrix RNA of the gfp gene. However, when 8A3 cells were incubated with a mixture of miRNA and recombinant pro-apo A-I and apo AK10, a decrease in fluorescence relative to the control cells incubated only with miRNA was not observed. Conclusion. It was shown that both the recombinant protein pro-apo A-I and the modified apoAK10 penetrate the transformed mouse macrophages of the line RAW264.7, but do not promote RNA interference in these cells.

Objective - to establish the inflammation features and 5-years survival in occupational chronic obstructive pulmonary disease (COPD) from silica dust exposure. Material and methods. It was an observational prospective cohort study. Occupational COPD patients ( n = 101) and healthy workers ( n = 51) exposed to silica dust enrolled. Comparison group - tobacco smokers with COPD ( n = 103). Control group - healthy people without occupational health risks ( n = 99). COPD was diagnosed according to GOLD 2011-2018 criteria. Groups were matched by length of service, smoking status, demographic characteristics. Levels of inflammatory cytokines, oxidative stress markers and metalloproteinases were measured in serum by enzyme-linked immunosorbent assay. Statistical analysis - ANCOVA and multiple linear regression. Survival was analyzed using Kaplan - Meier method and Cox proportional hazard regression. Results. Occupational COPD was characterized by high serum levels of monocyte chemoattractant protein 1 (MCP1), extracellular superoxide dismutase (SOD3), fibroblast growth factor 2 (FGF2) and 8-iso-prostaglandin F2α (8-iso-PGF2α). In healthy workers exposed to silica dust an increase in FGF2, МСР1 and SOD3 was revealed. In multiple regression models length of service and dust concentrations in the workplace air were associated with molecular factors. Inflammation features were associated with lung remodeling and function. Serum level of IL1β was associated with forced expiratory volume in 1 second (В = -3.4; р = 0.028), MMP 9 content - with residual volume ratio to total lung capacity (В = 1.3; р = 0.01) and FGF2 content - with diffusing lung capacity to CO (В = -2.4; р = 0.001). The 5-year cumulative death rate from pneumonia was higher in COPD due to dust when compared with tobacco smokers COPD (5 and 2 % respectively), while there was not differences in all cause survival. Multivariate analysis revealed that length of service, dust concentrations in the workplace air, serum concentration of М??1, MMP?9, FGF2 and 8-???-PGF2? are significantly associated with mortality. СР1, MMP 9, FGF2 and 8-изо-PGF2α are significantly associated with mortality. Conclusion. Occupational COPD from silica dust exposure is a specific endotype characterized by high risk of mortality from pneumonia. In workers exposed to dust for more than 10 years FGF2 is a perspective biomarker of high occupational COPD risk.

The aim of this study was to compare and analyze the effectiveness of protein markers of myocardial necrosis - heart-type fatty acid-binding protein (H-FABP) and the MB fraction of creatine phosphokinase (CPK-MB) in the dynamics of acute coronary syndrome. Material and methods. A total of 49 patients (57.1 ± 11,0 years) were examined, including 36 male patients (73.5 %) who were admitted to the City Clinical Hospital No. 34 of Novosibirsk with suspected acute coronary syndrome. The content of H-FABP in whole venous blood was evaluated for all patients upon admission to the hospital with the means of the immunochromatographic rapid test «CardioPBFA» (NPO «Biotest», Novosibirsk) with a sensitivity of 15 ng/ml. Determination of CPK-MB was carried out repeatedly in the first 48 hours from the beginning of the clinical manifestations of the disease, using immunochemiluminometric assay. Results and discussion. It was revealed that in patients with myocardial infarction (MI), CPK-MB content after 6-24 hours and also after 24-48 hours from the onset of pain was significantly higher than in patients without MI. H-FABP content 15 ng/ml and more, determined in the majority of patients in the first 6 hours from the onset of pain, was recorded much more often in MI presence than in MI absence. Using partial correlation analysis, it was determined that age influenced the association of MI with CPK-MB 6-24 hours after the onset of pain (which is probably due to the increase in the influence of a number of factors modulating the level of protein cardiac markers with age), and the correlation of MI with CPK-MB in 24-48 hours from the onset of pain did not depend on this factor ( r = 0.322; p = 0.46). In the regression model (χ² = 13.6; p = 0.001) it was revealed that H-FABP content 15 ng/ml and more regardless of age ( p = 0.006) is associated with the presence of MI in the patients, which confirms information about the high significance of identifying this H-FABP level in early diagnosis of myocardial infarction.

Study of the causes and mechanisms leading to sudden death is one of the most important goals in cardiology. Multiple studies suggest substantial role of mitochondrial dysfunction in the sudden death pathogenesis. Lack of ATP, excess of reactive oxygen species, and disruption of ionic balance in mitochondria are all able to provoke life-threatening arrhythmia. Mitochondrial DNA, which encodes several subunits of mitochondrial respiratory chain, is characterized by considerably high variability in human populations. It has been shown that cell respiration can depend on common mtDNA polymorphisms. In addition, there are data on associations of mtDNA polymorphisms with predisposition to cardiovascular diseases, including those associated with high risk of sudden death. The differences in cell bioenergetics between mtDNA genotypes do not influence myocardial function in normal state but may appear to be critical under acute ischemic conditions. So, mitochondrial genome should be considered as one of main components in the pathogenetics of sudden cardiac death.

The aim of the study was to study the relationship between the qualitative and quantitative characteristics of myelofibrosis and the clinical manifestations of chronic myeloid leukemia and chronic lymphocytic leukemia. Material and methods. A complex pathomorphological study of ilium bone trepanobioptates and a complex clinical-laboratory and instrumental examination of 154 patients with chronic myeloid leukemia and chronic lymphocytic leukemia were performed. Results. In patients in the chronic phase of chronic myeloid leukemia in the onset of the disease and with a loss of response to chemotherapy, the largest area of the spleen was detected with pronounced myelofibrosis, the smallest - in the absence of myelofibrosis. In patients in the onset or relapse of chronic lymphocytic leukemia, splenomegaly, hepatomegaly and generalized lymphadenopathy are most common in patients with myelofibrosis compared to patients without myelofibrosis. The expressed myelofibrosis in all cases was associated with hepatosplenomegaly. Comparing the morphometric and clinical data, it is established that in the chronic phase of chronic myeloid leukemia in the onset of the disease, the relative area of foci of initial myelofibrosis more than 60 %, the relative area of foci of pronounced myelofibrosis more than 40 %, and the granulocyte-megakaryocytic subtype of bone marrow tumor are associated with the development of relapse or progression of disease after 1st or 2nd line of chemotherapy. In the onset of chronic lymphocytic leukemia, the relative area of foci of initial myelofibrosis more than 20 %, the relative area of foci of pronounced myelofibrosis more than 11 %, and the diffuse type of bone marrow tumor lesion are associated with the development of relapse or progression of disease after 1st or 2nd line of chemotherapy.

Cell-mediated immunity parameters were studied in 26 patients (13 males, 13 females) aged 46 years (range: 39-51 years) with fistular type of chronic posttraumatic osteomyelitis of the humerus during the course of surgical treatment with the Ilizarov monofocal transosseous osteosynthesis. The study time-points were pre-surgery period and the following treatment stages: days 3, 7, 21 after osteosynthesis and day 1 after removal of the device. An obligatory criterion of inclusion was absence of postoperative complications and infection recurrence at least a year after removal of the apparatus. Control group were 30 healthy volunteers in the similar age (15 males, 15 females). Carriers of HCV, HIV, HBsAg and persons with concomitant somatic pathology that could affect the results of immunological study were not included. The study of subpopulation composition of the peripheral blood lymphocytes was carried out using laser flow cytometry. The parameters of cell-mediated immunity in patients with a fistular type of chronic posttraumatic osteomyelitis of the humerus were characterized by mild lymphopenia, increase in the number of cells of early and late activation of T lymphocytes (CD3⁺CD25⁺, CD3⁺HLA-DR⁺). Physiological response of the immune system to debridement of the purulent foci and transosseous osteosynthesis was normalization of the number of activated T-lymphocytes at the final stage of surgical treatment. In general, the dynamic changes of immunological indices were in favor of persistent arrest of the infection process and were confirmed by clinical observations.

Objective. To evaluate morphometric and hemodynamic changes in the prostate microcirculation under high-intensity focused ultrasound therapy (HIFU) combining with androgen deprivation in prostate cancer patients with a focus on the treatment effect assessment. Material and methods. 119 patients with localized adenocarcinoma of the prostate (Т2а-сN0M0) were examined prior to HIFU ablation and 3 to 36 months following the treatment. Microvascular density in the prostate tissue and hemodynamic parameters recorded by laser Doppler flowmetry at the prostate projection area (PPA) of the skin were analyzed comparatively. Results and discussion. Successful HIFU ablation (recurrence free survival at 3-year follow-up period) was associated with higher pretreatment microvascular density in the prostate tumor tissue and with a marked reduction of this parameter in the areas of residual non-neoplastic parenchyma after the ablation, which was accompanied by a significant decrease in PPA microhemodynamics. A course of androgen deprivation administered 1-3 months prior to ablation contributed to a moderate pre-HIFU reduction of tumor vascularization and PPA microcirculation index. As compared to HIFU monotherapy, cooperative use of HIFU and androgen blockade was associated with a relative decrease in the number of microvessels in the areas of residual neoplastic and non-neoplastic parenchyma in cases with local recurrence. A substantial increase of PPA microcirculation indices 6 or more months after HIFU ablation was found to be strongly associated with prostate cancer local recurrence which suggests that laser Doppler flowmetry could be used in the complex monitoring of the outcome from HIFU therapy for prostatic adenocarcinoma.

The study included 348 women with chronic cystitis who were divided into 3 age groups: Group 1 - 20 to 39 years old; Group 2 - 40 to 59 years old; Group 3 - elderly age (60 years and older). Bacterial flora was detected for the total sample in 35.3 % of patients without significant differences between age groups. The results indicate that infection is not the only cause affecting the development and persistence of chronic inflammation of the bladder. The incidences of leukoplakia of the bladder in age groups 1, 2 and 3 were 71 %, 50 % and 11 %, respectively. The survey results revealed increasing severity of symptoms such as pelvic pain and urination disorders with age. The evaluation of urination diaries revealed a decrease in the bladder effective volume with age and an increase in urination frequency in the daytime and at night. A significant increase in symptoms in the presence of leukoplakia was also revealed. High incidence of squamous metaplasia and leukoplakia and increased frequency of exacerbations of cystitis in young women may be associated with the catatoxic, highly reactive type of response of the transitional epithelium of the bladder. Increasing symptoms such as urinary disorders in older women with chronic cystitis may be caused by an adverse effect of systemic metabolic factors of the disease pathogenesis.

Purpose of the study - searching of new microRNA markers for differential diagnostics of different grade cerebral gliomas. Material and methods. Surgical material is tumor and externally unchanged brain tissue that was obtained from 41 patients with gliomas of different grade anaplasia. In 6 patients with cerebral glioma, a high-throughput Nanostring platform was used to determine the level of expression of 800 microRNAs. 37 patients with a similar pathology were subjected to real-time PCR, microRNA-128, 143, 144, 182, 183, 199b, 204, 7, 99a. Results and discussion: It has been established with the NanoString technology that the level of expression of miRNA 199b was significantly higher in gliomas of grade III and IV than in gliomas of grade II. In contrast, the expression level of miRNA-144 and miRNA-182 was reduced. There was also a significant 10-fold increase in the level of expression of microRNA-7 in tumors of grade IV in comparison with grade II. These differences in the expression of four microRNAs in these types of gliomas can be additional markers that distinguish rapidly growing malignant gliomas (grade III, IV) from slowly growing tumors (grade II) and timely assign an adequate comprehensive treatment.

Intrauterine growth restriction (IGR) is one of the leading causes of perinatal morbidity and mortality. The main mechanism underlying the delay in fetal growth is chronic placental dysfunction, in the form of a violation of adequate supply of oxygen and nutrients to the fetus, which leads to disruption of its growth and development. The delay in fetal growth is associated with a number of metabolic, cardiovascular, neurological disorders, respiratory diseases in early infancy and adulthood, requires long-term follow-up care and corrective therapy throughout the whole subsequent life. At present, a great interest is the study of molecular mechanisms for the formation of IGR, prenatal and postnatal complications of fetal growth retardation. The list of genetic causes of IGR grows with the development of molecular biology. In the review, we tried to cover the genetic, metabolic and endocrine factors responsible for the development of IGR. The in-depth study of the basic molecular mechanisms that form the IGR will allow expanding the range of preventive measures, diagnostic capabilities of early detection and timely correction of IGR, which will allow this group of patients to reduce perinatal morbidity, mortality and the risk of short-term and long-term consequences.

There are relevant areas of research aimed at studying the mechanisms of development and optimization of therapeutic approaches to hard controllable phenotypes of bronchial asthma in the disease prevention and treatment. This is the phenotype of bronchial asthma associated with obesity. The central function in the lungs physiology and pathology as well as in the obesity etiopathogenesis is assigned to lipids, which play a crucial role in maintaining the cell energy balance and the implementation of intracellular and intercellular signalization. Detailization of the role of alkyl-glycerols structure metabolites in the mechanisms of formation of the bronchial asthma phenotype in combination with obesity is an important area of modern research. In the analysis of modern studies on this problem, the strategy of treatment of bronchial asthma associated with obesity based on the General mechanisms of metabolic and signal disorders in these diseases was identified and justified. In recent years, due to the discovery of the relationship of disorders in the biosynthesis of diacyl and alk(en)yl acyl phospholipids with respiratory diseases and obesity, there is a growing interest in their study as promising therapeutic targets. The introduction of anti-inflammatory natural compounds, which include alkyl-glycerols contained in marine hydrobionts, will modify the intracellular signaling pathways responsible for inflammatory cell activation in bronchial asthma associated with obesity.

Purpose of the study - to evaluate the effectiveness of transcranial magnetotherapy in the rehabilitation of patients with arterial hypertension (AH) combined with chronic cerebrovascular diseases (CCVD). Material and methods. Fifty patients with AH combined with CCVD aged 20 to 75 years, with an average age of 62.1 ± 2.0 years were examined and treated. Clinical examination included: collection of complaints and anamnesis of life, clinical laboratory and instrumental methods of examination, assessment of quality of life related to health (according to the SF-36 questionnaire). All patients were randomized into 2 groups, comparable in age, sex, clinical and functional parameters: experimental ( n = 24) and control ( n = 26). Patients of the control group received basic medicinal therapy for 2 weeks. Patients of the experimental group, on the background of basic medicinal therapy, received transcranial magnetotherapy. Course of 10 procedures. The effectiveness of rehabilitation was carried out before and after the course on the dynamics of hemodynamic and clinical parameters; indicators of quality of life. Results. In patients of the experimental group, in comparison with the control group, there was a more pronounced positive dynamics with a greater reduction in blood pressure, the frequency of characteristic clinical symptoms; a more pronounced improvement in the quality of life after a course of action. Thus, the mean value of pulse blood pressure decreased in the experimental group by 24.7 %, in the control group by 18.7 %. The frequency of occurrence of vertigo after the course was statistically significantly decreased in the main group by 45.9 %, in the control group by 23.1 %. Conclusion. The effectiveness of transcranial magnetotherapy in the rehabilitative treatment of patients with AH combined with CCVD is shown, which makes it possible to recommend this physiotherapeutic method for personified non-medicinal rehabilitation of this category of patients in a hospital.

The World Health Organization recognized the overweight as the new non-infectious “epidemic of the XXI century”. By the beginning of the century, almost all countries in the world reported an increase in the prevalence of overweight, with over 400 million adults suffering from obesity and a further increase in its prevalence. The aim of the study was to determine the levels and prevalence of abdominal obesity in accordance with different criteria for assessing the able-bodied age of an open population of a medium-urbanized Siberian city in men. Material and methods. A one-time epidemiological study was conducted on a representative sample, formed from the electoral lists of male members aged 25-64 years in one of the administrative districts of Tyumen. For the analysis of the abdominal obesity, the criteria of the metabolic syndrome of International Diabetes Federation (IDF, 2005), National Cholesterol Education Program Expert Panel, Adult Treatment Panel III (NCEP ATP III, 2004), All-Russian Scientific Society of 2009) were used. Results and discussion. There was a directed age trend in the waist circumference with a significant increase in the AW levels in each subsequent age group by the levels of the central (abdominal) type of obesity in the Tyumen population. The standardized prevalence rate of abdominal obesity in the male population of 25-64 years in Tyumen was 42.6 % according to the IDF criteria, 17.9 % according to the NCEP ATP III criteria, 38.8 % according to the criteria of the VNOK, positive criteria were established for all criteria with age in the younger and older age categories. The results of this study can serve as a scientific base and starting point for the formation of comprehensive preventive programs among men of working age in Tyumen and other urbanized Russian cities.

The aim of the study was to evaluate the susceptibility to antibiotics of Klebsiella pneumoniae isolates in the Republic of Sakha (Yakutia), according to the AMRmap database. Material and methods. Data of online platform AMRmap in 2010-2016 have been used for evaluation of the sensitivity of K. pneumoniae isolates to antibiotics. Results and discussion. K. pneumoniae isolates comprised 35,7 % of all bacterial nosocomial isolates ( n = 195) and 30,1 % of community-acquired isolates ( n = 382) respectively. Most of the isolates were insusceptible to common antibiotics: aminoglycosides (gentamicin, tobramycin, netilmicin) - 50-78 %; chloramphenicol - 36-43 %, cephalosporins III-V generation (ceftazidime, cefotaxime, zepefin, ceftarolin) - 83-100 %, penicillin drugs with inhibitor of beta-lactamases (ticarcillin-clavulanate, amoxicillin-clavulanate) - 83-98 % monobactams (aztreonam) - 87-95 %, semi-synthetic penicillins of broad spectrum of action (ampicillin) - 100 %, sulfonamides (trimethoprim-sulfamethoxazole) - 53-76 %, fluoroquinolones (ciprofloxacin) - 77 %. At present the next preparations can be effective against K. pneumonia: amikacin (sensitivity 96-100 %), ceftazidime-avibactam (95-97 %), tigecycline (97-100 %), carbapenems (87-97 %), in some cases, phosphomycin (77 %) and piperacillin-tazobactam (64-71 %). Conclusion. The spectrum of drugs for the treatment of infections caused by K. pneumoniae is extremely limited. The further spread of resistance to carbapenems poses a threat of ineffectiveness in the treatment of severe infections. In these conditions, measures are needed to limit the unjustified use of carbapenems. The indicators of resistance of K. pneumoniae to antibiotics should be taken into account not only for the effective treatment of patients, but also for optimizing the costs of regional health care, for example when planning procurement of medicines for hospitals

Aim of the study - to estimate the indicators of the central haemodynamics of children of the first class in Gorno-Altaysk when conducting one-stage functional Martinet - Kushelevsky’s test depending on the level of salivary cortisol. Material and methods. An object of the research was the students of the first class of schools No. 7, 8 and 12 of Gorno-Altaysk (78 children, including 33 boys and 45 girls in the age of 7-8 years). Content of salivary cortisol and indicators of the central haemodynamics were determined when performing one-stage functional Martinet - Kushelevsky’s test (heart rate, arterial blood pressure, systolic and minute blood volume). The type of cardiovascular system reaction, the reaction quality indicator and blood circulation efficiency were defined on the basis of restoration dynamics of heart rate and arterial pressure. Correlation analysis of cardiovascular system indicators and level of salivary cortisol was carried out. Results and discussion. Cortisol level at the examined children didn’t go beyond reference values. The normotonical type of cardiovascular system reaction to physical activity was noted at 54 % of children (42 of 78), atypical types of reaction were revealed at the others: asthenic at 38 % (30 of 78), dystonic at 6 % (5 of 78) and step-type at 1 % (1 of 78). The indicator values of reaction quality of examined children demonstrate that cardiovascular system adaptation to physical activity at children is carried out due to insignificant increase in pulse pressure and excessive increase in heart rate. The performance indicator of low circulation values are caused by significant increase in heart rate in relation to the systolic pressure (the rate of circulation value is lower than optimum level at 61 % of children). Restoration of heart rate after loading at the examined children took place for the 3rd minute however the mode of this indicator restoration is of decremental character being a sign of cardiovascular system unstable condition. The positive correlation of average degree between the salivary cortisol level and HR indicators of both after physical activity and during restoration is revealed ( p < 0,05). Therefore, the cardiovascular system of children with rather high rates of free cortisol in saliva is notable for the bigger reactivity to physical activity. Conclusion. The atypical type of cardiovascular systems reaction to standard physical activity and the decremental nature of HR restoration is revealed at 46 % examined children of the first class of general education institutions No. 7, 8 and 12 of Gorno-Altaysk. The significant increase in HR after physical activity is revealed at children with higher level of salivary cortisol.

The purpose of the study was to assess work-related diseases of blood circulation among workers occupationally exposed to noise in mineral extraction. Material and methods. Working conditions, health status of 1481 workers of leading occupations of oil and ore minerals extraction along with the assessment of cardio-vascular system functional state according to electrocardiography, eye fundus vessels, systemic microhemodynamics and blood microcirculation of bulbar conjunctiva have been studied. Results and discussion. Workers of these occupations are exposed to a complex of work environment and work process factors with occupational noise as a priority one. Blood circulation diseases are detected two times more frequently among workers than in the control group. Arterial hypertension frequency increases with age and work experience; a reliable increase is observed among individuals with work experience of 11-15 years and more than 15 years as compared to the group of workers with 6-10-year work experience and less than 5 years. On electrocardiographic examination, changes in the heart have been revealed in 54.2 % of workers engaged in ore extraction and 42.9 % of workers of oil extraction. Cerebrovascular diseases in most workers have been diagnosed along with arterial hypertension and atherosclerotic processes confirmed by changes in the eye fundus vessels. Thus, the elevated prevalence and an increase in arterial hypertension frequency due to work experience do not exclude potential impact of hazardous working conditions on its formation. The significant role of working conditions for arterial hypertension development has been established among operators of overhaul and underground repair of wells, drift miners, machinists of loading and delivery machines, aggregates and excavators. This is the foundation for the development of measures for creating safe working conditions and prevention of blood circulation diseases.

Purpose: to estimate influence of volume malformation on the course of structural epilepsy and neurophysiological data. Materials and methods: The study included 207 patients with brain AVM and seizure. 81 patients (pts) were performed by EEG before and after treatment. 103 patients underwent total invasive treatment, 96 pts - partial embolization and 8 pts - subtotal embolization. Follow up was 12 months. Evaluation of treatment was carried out on a scale Engel and ILAE. Results: Patients underwent a total treatment of grade I on the Engel scale were in 74.8 % (77 pts), and 1 grade on the ILAE scale were in 58.3 % (60 pts). Patients with a partial embolization of grade I on the Engel scale were in 40.4 % (42 pts), and 1 grade on the ILAE scale were in 20.2 % (21 pts), which is significantly worse than in the group with total treatment (on the Engel scale F = 5.1, ILAE - F = 5.8, р < 0.01). The subtotal embolization let get the grade I on the Engel scale in 62.5 % (5 pts). There was no significant difference to total treatment and partial embolization ( p > 0.05). By EEG investigated: epileptic and slow-wave activity, focus on the hemisphere, where AVM is localized, disorganization and diffuse changes in bioelectric activity (BA). The BA improvement was in 17.1 % pts in the total treatment group, and in partial embolization group - in 2.5 % pts. However, these data were not significant different ( p = 0.065). So, total treatment of brain AVMs gives the better control of seizure and more often improves EEG data.