BIOMEDICINE
The aim of the study was to evaluate microcirculatory and metabolic changes in damaged skeletal muscles in rats with experimental explosive trauma with acute blood loss. Material and methods. An experimental model of explosive damage to the soft tissues of the pelvic limb in rats was used to assess microcirculation and metabolic activity in the muscles of the area of the explosive wound by laser Doppler flowmetry and laser fluorescence diagnostics using the LAKK-M device. Results and discussion. It was found that during the entire follow-up period (28 days), pronounced disorders of microcirculation and metabolism were formed in the damaged muscles. Tissue perfusion was significantly reduced, which is confirmed by a change in the coefficient of variation of the microcirculation index, the value of which was lower by 36–51 % (p < 0.05) in all follow-up periods in animals from the intact group, and the maximum decrease in the indicator was observed by 28 days (6.7 (6.3; 7.4) %, at p < 0.05). Tissue metabolism was rearranged in the direction of activation of the anaerobic pathway: there was a decrease in the index of specific oxygen consumption by the tissue – by 2.3 times (p < 0.05), the fluorescent index of oxygen consumption by the tissues – by 60 % (p < 0.05), the integral index of oxygen exchange efficiency by an average of 8.5 times (p < 0.05) relative to healthy animals, which generally indicated weak oxygen utilization by the tissues. These disorders of metabolism and oxygen consumption by the tissues of the damaged area persisted throughout the experiment with a slight positive dynamics by the end of the observation period. Conclusion. The obtained data are a pathogenetic justification for the development of means for the local correction of microcirculatory and metabolic disorders in the muscles in the case of explosive trauma in the post-traumatic period.
The aim of research was to study the oxidized dextran protection effect against hepatic parenchyma defect at combinated acute and chronic toxicity of ethyl alcohol and tetrachloromethane solutions. Materials and methods. 150 male Wistar rats were injected by toxicants with intraperitoneal administration: 50 % CCl4 in olive oil solution and 5 % oxidized dextran (OD) aqueous solution with molecular weight 40 kDa and peroral 6.5 % ethyl alcohol aqueous solution. Tetrachloromethane was injected once a day, and then only ethyl alcohol aqueous solution was administrated 1 time per day during 3 days. The ethyl alcohol aqueous solution was not administered on the days of the of tetrachlomethane and OD injections. OD has been administered from the 1st day of the toxicants injection till 60 days. OD without toxicants has been injected for the next 30 days. Results and discussion. In animals that were injected only with toxicants, hepatocytes were in a state of vacuolar dystrophy, which occupied slightly more than 40 % of the organ parenchyma, and hepatocytes in a state of necrosis, which occupied from 37 to 28 % of the parenchyma at different periods of observation. The OD inclusion in the scheme for the prevention of necrotic complications reduced them from 3 to 4 times more than in animals that did not receive OD. The data obtained indicate the OD high hepatoprotective effectiveness.
The aim of the study was to determine the efficacy of recombinant human interferon lambda 1 (IFN-λ1) against human adenovirus serotype 5 in a culture of human conjunctival cells Chang conjunctiva clone 1-5c-4. Material and methods. The study design consisted of three experimental schemes, reflecting a prophylactic and two options for a therapeutic and prophylactic treatment regimen (with the constant presence of the virus in the culture medium and with its removal after adsorption). The antiviral activity of IFN-λ1 was determined by the number of viable cells after exposure to the virus (MTT test). Results and discussion. It has been established that IFN-λ1 has antiviral activity against human adenovirus in vitro under a prophylactic and therapeutic-prophylactic scheme of administration at an infection dose of 1 and 10 TCID50 (50% tissue culture infectious dose), but not at an infection dose of 100 TCID50. The antiviral effect of the use of IFN-λ1 in a therapeutic and prophylactic regimen at an infection dose of 1 TCID50 was comparable to that of IFN-α. At the same time, both interferons did not have a toxic effect on the cell culture even at a concentration of 84 and 58 μg/ml, respectively. The antiviral activity and the absence of cytotoxic action provide the basis for further study of the possibility of development of based on IFN-λ1 drug for eye conjunctiva viral diseases treatment.
The aim of the study was to assess the level of NAD+ in the brain of mice treated with beta-amyloid (Aβ), as well as to determine the activity of ADP-ribosyl cyclase/CD38 and the number of CD38-immunopositive neurons, astrocytes and endothelial cells. Material and methods. The Alzheimer’s disease model was reproduced by intrahippocampal administration of Aβ to C57BL/6 mice. Determination of the NAD+ level in the extracellular fluid of the brain and in the hippocampal tissue was carried out by spectrophotometric analysis. Evaluation of the enzymatic activity of ADP-ribosyl cyclase / CD38 was carried out by the fluorimetric method, determination of the number of CD38-immunopositive cells by the immunohistochemistry method. Results and discussion. The level of NAD+ was significantly increased in the hippocampal tissue in mice after administration of Aβ, while the level of extracellular NAD+ did not change. The activity of ADP-ribosyl cyclase / CD38 in the hippocampal tissue did not change, but the number of CD38-immunopositive neurons decreased, and the number of CD38+ endothelial cells increased in the hippocampus of mice after administration of Aβ. Conclusion. Opposite changes in the expression of ADP-ribosyl cyclase / CD38 in neurons and endotheliocytes correspond to different metabolic states of these types of cells and, along with an increased intracellular pool of NAD+ in experimental Alzheimer’s disease, reflect an adaptive stress response to Aβ administration.
An experimental study is devoted to the study of the effect of Astragalus vulpinus extract on lipid peroxidation processes in the hypothalamic region under conditions of lipopolysaccharide immune stress. Material and methods. Experiments were performed on white male rats 6-8 months of age. In all series of experiments, animals were divided into groups (n = 10): 1st – control individuals receiving distilled water in an equivalent volume; 2nd – rats with immune stress model; 3rd – individuals treated with Astragalus vulpinus extract against the background of immune stress. The test extract and distilled water were administered once a day intragastrically with a 50 mg/kg probe for 14 days. Immune stress was formed by single intraperitoneal administration of lipopolysaccharide pyrogenal isolated from Salmonella typhi microbial cells. The intensity of free radical oxidation processes was studied by thiobarbituric acid reactive substances (TBARS) content, spontaneous and ascorbate-dependent lipid peroxidation rate and catalase activity were also determined. Results. According to the results of the experiment, it was revealed that immune stress is accompanied by the activation of free-radical oxidation processes, as evidenced by an increase in the concentration of products of this process and the activity of the body’s antioxidant protection enzyme catalase. Assessment of the effect of Astragalus vulpinus herb extract on the free radical potential in the hypothalamic region against the background of the action of lipopolysaccharide-induced immune stress showed that the studied extract exhibits pronounced stress-protective and antioxidant properties characterized by changing the intensity of lipid peroxidation processes and by increase of catalase activity in the tissue of the hypothalamic brain region. Conclusions. Astragalus vulpinus herb extract has been proven to exhibit antioxidant effects by restoring activity of free radical processes.
Mesenchymal stem cells (MSCs) are considered as a promising tool for the treatment of inflammatory and degenerative diseases, but their effectiveness is associated with the survival of cells in an unfavorable microenvironment. Erythropoietin exhibits an anti-apoptotic effect for non-hematopoietic cells of the human and animal body. The aim of the study was to evaluate the morphofunctional properties of MSCs cultured with erythropoietin. Material and methods. MSCs were obtained from bone marrow aspirate of patients with chronic heart failure. The primary culture of MSCs-EPO was obtained by growth MSCs of the 4th passage for 7-8 days with erythropoietin at a dose of 33 IU/mL. The phenotype, differentiation in the adipogenic and osteogenic directions, proliferation, migration, and production of nitric oxide of MSCs were studied. Results and discussion. The study revealed that the cultivation of MSCs with erythropoietin contributes to an increase in the expression of the main surface molecules that characterize the cells belonging to true MSCs, possess to differentiated of MSCs into adipocytes and osteoblasts, a change in the expression levels of adhesion molecules, a decrease in the level of apoptosis, increased cell migration during the induction of oxidative stress and hyperglycemia. Conclusion. Cultivation of MSCs with erythropoietin increases the resistance of cells to adverse microenvironment factors.
A comparative study of the effect of a matrix based on porous aluminum oxide and a silicon organic polymer polydimethylsiloxane (PDMS) (А12O3@PDMS) and a matrix complex with copper and zinc sorbed on its surface (Cu@Zn- А12O3@PDMS) on the functional properties of fibroblasts has been carried out. Material and methods. The effect of the Cu@Zn- А12O3@PDMS complex and the matrix on the cell proliferative potential (MTT test), apoptosis, necrosis and the production of stable nitric oxide (NO) metabolites were studied in an in vitro experiment with a human embryo fibroblast cell line (HEF-15). Results. The compared samples of Cu@Zn-A12O3@PDMS and Al2O3@PDMS are similar in their physico-chemical properties. Study of HEF-15 functional potential indicates a higher level of cell proliferation and ability to produce NO after contact with the complex. There was no significant increase in apoptosis and necrosis of HEF-15 in the presence of samples of the complex and the carrier. Conclusion. The absence of a significant negative effect of the tested samples on the functional status of cells of the FEH-15 line (proliferation, apoptosis, necrosis, NO secretion) in vitro allows the use of the Cu@Zn-A12O3@PDMS complex for further analysis of its safety in experimental models of skin defects in animals.
It has been epidemiologically established that the rate of primary cholangiocarcinomas increases greatly in the ObIrtysh basin which is hyperendemic for helminth Opisthorchis felineus in comparison with other regions where the population is not infested. In this connection chronic opisthorchiasis is considered as facultative liver precancer. The study of cholangiocarcinogenesis mechanisms will allow developing pathogenetic approaches to prevention of this tumor. Aim of the study was to investigate the significance of microbiota of the hepatobiliary tract of chronic opisthorchiasis patients in changing of biochemical composition of bile and investigation of its biological influence on somatic cells membrane. Material and methods. Objects of research: bacteria; inbred mice infected by opisthorchis; samples of bile, cultures of human embryo fibroblasts and splenocytes of inbred mice in vitro; blood plasma; standard primary and secondary bile acids. We studied: species of bacteria colonizing bile ducts; quantitative and qualitative composition of bile acids, and level of diene conjugates and malondialdehyde in duct bile samples; biological activity of bile on processes of lipid peroxidation of cell membranes in vitro; influence of bile and lipid peroxidation products on cytomembrane permeability; activity of antioxidant systems of the body. Results and discussion. It was found out, that bile of patients with chronic opisthorchiasis in majority of cases (77.0 %) was infected by different species of bacteria. In 30.0 % of cases certain types of intestinal bacteria (Proteus vulgaris, P. mirabilis, Citrobacter freundii, Bacteroides alcaligues faecalis, Clostridium, Streptococcus faecalis, Escherichia coli) change biochemical composition of duct bile – deconjugated primary and secondary bile acids and also high level of total bile acids are detected. Bile of the above biochemical composition, against the background of depletion of antioxidant system, induces activation of cell membrane lipid peroxidation processes and significantly increases their permeability to toxic components of bile. These processes are promotor in cholangiocarcinogenesis.
CLINICAL MEDICINE
A number of studies have now been conducted confirming the relationship between arterial hypertension (AH) and nonalcoholic fatty liver disease (NAFLD). It has been proved that the presence of AH increases or provokes the development of NAFLD. A study of telmisartan effectiveness in combination with atorvastatin and ursodeoxycholic acid (UDCA) in patients with AH and NAFLD was carried out in this article. Material and methods. The study included 39 patients diagnosed with arterial hypertension in combination with NAFLD, who were treated with a combination of drugs: Telmisartan, Atorvastatin and UDCA for 12 weeks. The comparison group consisted of 33 patients with NAFLD who received basic NAFLD therapy without telmisartan and atorvastatin. The study analyzed the efficacy of the prescription of this combination on the clinical condition of patients with AH combined with NAFLD, their hemodynamic parameters, the levels of blood lipid spectrum, IL-6, leptin, adiponectin, and the dynamics of echocardiographic and ultrasonographic parameters. Results and discussion. It has been revealed, that application of telmisartan, atorvastatin and UZHK combination for 12 weeks significantly reduced BP levels to the target values, improved hemodynamic indexes, led to reduction of atherogenic components of blood lipid spectrum. And also prescription of this combination decreased IL-6 and leptin levels, increased adiponectin content, which contributed to improvement of the general state of patients, decrease in the severity of clinical and functional manifestations of NAFLD.
An increase in the proportion of comorbid cardiac patients with primary nosologies such as arterial hypertension and atherosclerosis actualizes the search for optimal approaches to their diagnosis and treatment. The emerging pathogenetic mechanisms of concomitant diseases must be taken into account on an individual basis. Aim of the study was to investigate the patterns of atherosclerotic changes in carotid arteries in patients with coronary heart disease who underwent percutaneous transluminal coronary angioplasty and their correlation with biochemical and hemodynamic markers of atherosclerosis. Material and methods. 53 patients with coronary heart disease (CHD) were examined and treated in the clinic of the Federal Research Center of Fundamental and Translational Medicine. The average age of the patients was 64.73 ± 1.66 years. A comprehensive clinical laboratory examination was conducted, including the blood lipids test to measure content of total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, as well as serum markers of systemic inflammation (concentration of C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR)) and carotid artery duplex scan. Results. A direct correlation between the severity of atherosclerotic changes in the carotid arteries and indicators of systemic inflammation, i.e. CRP, ESR and fibrinogen was found. The study also revealed greater severity of atherosclerotic stenosis of the carotid arteries in patients with coronary artery disease who underwent percutaneous transluminal coronary angioplasty with coronary artery stenting compared to patients without any intervention. Conclusion. The obtained data indicate the effectiveness of ultrasound scan of the carotid arteries for the early diagnosis of multifocal atherosclerosis for timely treatment and prevention of cardiovascular polymorbidity in patients with a cardiovascular profile.
Mediastinitis as complications of traumas and esophagus perforations are ill-controlled and characterized with high mortality. Yet clinical characteristics and therapeutic controllability of contact odontogenic mediastinitis are not covered enough in medical literature. Aim of the study was to investigate clinical characteristics and to analyze treatment results of odontogenic purulent mediastinitis according to data of pilot monocenter observational study. Material and methods. The results of treatment of the patients with odontogenic mediastinitis were analyzed in groups: panmediastinitis (8 participants) and posterior upper mediastinitis (12 participants). The following indexes were compared: body temperature, content of C-reactive protein, leucocytes, thrombocytes, creatinine, 24-hour and cumulative fluid electrolyte balance reproduced in hospitals of any equipment levels with using of criteria of nonparametric statistics for excluding of false positive results. Results. Causative agents of the infectious process were found in 65 % of patients in bacteriological study. The mortality was 5 %; the process controllability in conditions of described techniques of anesthesiology and intensive therapy has been shown, the danger of infusive overload of the interstitium of the lungs has been demonstrated.
The aim of this work is to study the electrical and viscoelastic parameters of erythrocytes for patients with inflammatory bowel diseases (IBD), examined in dynamics, as possible predictors of exacerbation of the disease. Material and methods. In dynamics, 23 patients with IBD (37.9 ± 4.3 years) were examined. The first examination was carried out in the stage of exacerbation, the second – after 6–12 months – in the stage of remission of IBD. Additionally, 36 patients with IBD in remission were examined to assess the predictive capabilities of erythrocyte parameters with subsequent monitoring of their condition for 6–12 months. The electrical and viscoelastic parameters of erythrocytes were investigated by dielectrophoresis. Statistical processing was carried out using a system of machine learning methods – Random Forest, MATLAB (R2019a, MathWorks). Results and discussion. The parameters of erythrocytes, which are predictors of exacerbation of IBD, were revealed: an increase in the proportion of deformed cells (p = 0.0001); altered nature of the erythrocyte surface (p = 0.011); increased electrical conductivity of membranes (p = 0.0019); reduced dipole moment (p = 0.0015), the rate of directional movement of erythrocytes to the electrodes (p = 0.005) (paired and unpaired Volcano plot methods), reduced deformation amplitude at a frequency of 5×105 Hz (p = 0.009), capacity of erythrocyte membranes (p = 0.029 ) (unpaired Volcano plot method). Indicators associated with changes in the charge of cells, the structure of erythrocyte membranes and the level of energy metabolism of the cell turned out to be significant. A high diagnostic accuracy of these indicators was established as predictors: the proportion of deformed cells (AUC 0.939), a summarized viscosity index (AUC 0.932). Cluster analysis of the values of erythrocyte parameters – predictors of exacerbation made it possible to stratify the risk of exacerbation: at the most altered levels of parameters – the development of exacerbation after 2.5–4.5 months, intermediate levels – after 4–6 months, minimally changed – after 8–12 months (predictive accuracy – 92 %). Conclusions. The revealed electrical and viscoelastic parameters of erythrocytes should be considered as promising predictors of exacerbation in patients with IBD.
REVIEWS
The ongoing COVID-19 pandemic has highlighted significant gaps in human protection from infection. There is a real and fairly high probability of new infections that pose a danger to humans. To combat (prevention and treatment) this kind of infections, new types of drugs are needed, which differ in their mechanism of action from existing antimicrobial agents and vaccines, and thus complement them. These drugs should have complex universal activity against pathogens, regardless of their type (bacteria, viruses, fungi, protozoa) and, in general, increase the resistance of the macroorganism to infection by pathogenic agents, stimulate nonspecific immunity, both general and local. In this regard, preparations of nanostructured silver are promising. The properties of silver nanoparticles depend on their structure, shape, size, morphology, ligand environment and preparation method. Argovit represents nanosilver formulation with optimized biochemical and toxicological characteristics. Argovit effectiveness for combating infectious pathogens in various fields of medicine was shown for: intestinal infections of various etiologies; acute respiratory viral infections and associated bacterial complications; purulent surgery, diabetic foot; drug resistant forms of tuberculosis; viral infections caused by both DNA and RNA viruses. In the clinic, argovit effectiveness in protection from coronavirus infection and for treatment of the early stages of COVID-19 disease on volunteers was shown.
PREVENTIVE MEDICINE
Arterial hypertension remains one of the most common diseases in the developed countries of the world, while there is a tendency to increase the frequency of arterial hypertension as the level of urbanization increases. According to epidemiological studies in the Siberian region at the end of the last century, an unfavorable epidemiological situation regarding the prevalence of hypertension among people of economically desirable age was revealed both in men of organized populations employed in the oil and gas complex of the Far North region and in open urban populations of varying degrees of urbanization. The aim of the study was to determine the dynamics of the levels and prevalence of arterial hypertension in men of working age over a 15-year period of monitoring the open population of the mid-urban city of Western Siberia. Material and methods. Two simultaneous epidemiological studies were conducted among men aged 25–64 over four decades of life in the Central Administrative District of Tyumen in 1996 and 2010. The screening participant was informed about the history of high blood pressure and taking antihypertensive drugs for two weeks before the examination was taken into account. AH was recorded at systolic blood pressure levels of 140 mm Hg. Art. and / or diastolic blood pressure ≥ 90 mm RT. Art. Results. According to the 15-year monitoring of men in the open population of the mid-urbanized city of Western Siberia, a positive trend was identified for a decrease in the prevalence of hypertension due to the age category of 25–34 years. A decrease in the prevalence of hypertension in young men over a 15-year period of the population monitoring was established in connection with the positive dynamics of a decrease in systolic blood pressure levels in the age category of 25–34 years. Conclusion. The results of this work can serve as a basis and starting point for the development of a comprehensive preventive program in the open population of Tyumen, the effectiveness of which largely depends on an objective assessment of the motion vector of the epidemiological situation with respect to the main risk factors for cardiovascular diseases in various age categories.
The prevalence of metabolic syndrome components at the population level was determined mainly in age-limited contingents, by criteria for assessing metabolic syndrome, or on selective samples of the population, while conducting correct epidemiological studies in open female populations to study the prevalence of metabolic syndrome components according to various assessment criteria seems to be extremely relevant. Aim of the study was to establish the prevalence of metabolic syndrome components in an open female population according to different assessment criteria (on the model of Tyumen). Material and methods. A cross-sectional epidemiological study was carried out among females in one of the administrative districts of Tyumen. A representative sample was formed from electoral lists among women 25-64 years old by the method of «random numbers» – 1000 subjects (250 persons in four decades of life). The response to the study was 70.3 %. The NCEP ATP III (2004) and IDF (2005) criteria for assessing the metabolic syndrome were used for the analysis. Results. In an open population of a moderately urbanized city of Western Siberia among women 25-64 years old, a high prevalence of abdominal obesity was revealed according to various criteria for assessing agestandardized indicator (33.5 and 49.8 %), a positive relationship with age was determined. The prevalence of arterial hypertension, hyperglycemia and hypertriglyceridemia HTG occupies the middle position with a significant increase in indicators in older age categories. In women of the urban population, a high prevalence of high density lipoprotein hypocholesterolemia was revealed in young and middle age (from 18.5 to 31.3 %). Conclusion. The obtained data on the prevalence of metabolic syndrome components in women in an open population help to identify risk groups for the development of cardiovascular diseases and to outline measures for primary prevention among the population of a medium-urbanized city of Western Siberia.
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