The purpose of the research was to identify changes in immune and hormonal regulation in patients with hand-arm vibration syndrome and sensorineural hearing loss to substantiate informative biomarkers.

Materials and methods. Men with occupational injury induced by exposure to vibration and noise were examined. The first group included 26 people diagnosed with stage 1 and 2 hand-arm vibration syndrome. The second group consisted of 38 patients diagnosed with sensorineural hearing loss. Serum levels of cortisol, dehydroepiandrosterone sulfate, prolactin, free triiodothyronine (T3), free thyroxine  (T4), thyroid-stimulating hormone (TSH), and interleukins IL-1β, IL-8, IL-10 were determined by enzyme-linked immunosorbent assay.

Results. The results of the study revealed the peculiarities in the immune and hormonal regulation in hand-arm vibration syndrome and sensorineural hearing loss. More pronounced changes were observed in sensorineural hearing loss. A common pattern in patients with hand-arm vibration syndrome and sensorineural hearing loss was an increase in cortisol, prolactin and IL-8 and a decrease in free T4 and IL-1β. Differences in the identified changes in the immune and hormonal status were characterized by increased TSH production in the first group, and increased free T 3 production and decreased IL-10 in the second group. In hand-arm vibration syndrome, high levels of cortisol were accompanied by a decrease in the IL-1β and IL-10 concentrations. In sensorineural hearing loss, an increase in the prolactin concentration was accompanied by increased production of IL-8.

Conclusions. The identified features of immune and hormonal relations may be induced by the intensity of cortisol and prolactin production under the effects of various physical factors. Persistent high levels of cortisol and prolactin in the examined patients are important pathogenetically significant factors in the development of the disease. New laboratory indicators (IL-4, prolactin, free T3) for additional diagnosis of occupational sensorineural hearing loss were identified.

Аim. To study the 8-year dynamics of somatic pathology in residents of the Khanty-Mansi Autonomous Okrug – Yugra.

Materials and methods. The article analyzes the migration of the population of the Far North and the dynamics of the incidence of chronic non-infectious pathology among residents of territories equated to the Far North – the Khanty-Mansi Autonomous Okrug – Yugra, based on literature data and officially registered statistics for clinical and statistical groups for the period 2010–2017.

Results. The analysis revealed the leading groups of somatic pathology in the Khanty-Mansi Autonomous Okrug – Yugra. The indicators of population dynamics of the territories of the Far North of Russia were estimated. 

Conclusions. The study identified patterns in different flows of the Russian population in and from the North, the incidence rate (defined by the leading group of diseases) and its dynamics, characteristic of the territories equated to the Far North. The obtained data make it possible to identify priority research areas aimed at analyzing the frequency of diseases of internal organs in the territories equated to the Far North, the features of their course and outcomes as well as to develop effective programs of primary and secondary prevention of these diseases.

The purpose was to study the structural and functional parameters of erythrocyte membranes in the blood of patients with gastric cancer (GC) – adenocarcinoma, depending on its grade, signet ring cell carcinoma (SRCC), and combined gastric lesions (CGL).

Materials and methods. The membrane fluidity in the area of the lipid bilayer and protein-lipid contacts, the polarity of the lipid bilayer and the immersion of proteins in the lipid matrix of the membrane in red blood cells were evaluated by fluorimetry using the hydrophobic pyrene-based probe. The study included 86 patients with GC divided into six groups: well- and moderately-differentiated adenocarcinoma (G1-2); poorly-differentiated adenocarcinoma (G3); SRCC; CGL and two groups of patients with a component of undifferentiated cancer: G4 + SRCC and G4 + G2-3. The results of the study were also analyzed in patients with serosal invasion and the spread to adjacent structures (T4 according to the TNM classification of malignant tumors) and in patients with stage IV disease.

Results. In all groups of GC patients, an increase in the membrane fluidity was observed. It was more pronounced in the zone of protein-lipid contacts, but it was also observed in the lipid bilayer. The membrane fluidity increased together with the grade of adenocarcinoma and was maximal when there were undifferentiated cells in stomach tumors, reaching 93.8% in the zone of protein-lipid contacts and 54.1% in the lipid bilayer, compared with healthy people (20 donors). An increase in the polarity of the lipid phase was also observed; it was most pronounced (by 7–8%, p = 0.002–0.003) in adenocarcinoma patients with undifferentiated cells and with stage IV disease. A change in the immersion of proteins in the lipid matrix of erythrocytes was less characteristic of GC, compared with other cancers (breast, lung tumors, gynecological oncopathology, etc.).

Conclusions. Changes in the structural and functional properties of erythrocyte membranes reflect the state of the disease in patients with gastric cancer and may be important for predicting the course of the disease and the success of treatment.

The aim of the research was to establish the role of inflammation mediators and iron metabolism in the pathogenesis of various types of anemic syndrome in pregnant women with gestational diabetes mellitus (GDM).

Materials and methods. 32 pregnant patients with GDM were examined; 14 of them had iron deficiency anemia, 18 – anemia of chronic diseases. The enzyme-linked immunosorbent assay was used to determine the concentration of IL-6, hepcidin and a soluble receptor for transferrin in the blood serum of pregnant women, the concentrations of C-reactive protein and transferrin were determined with the method of turbidimetry.

Results. It was shown that women with GDM had higher IL-6 level compared to healthy pregnant women, and the concentration of IL-6 did not depend on the type of anemic syndrome. The C-reactive protein concentration was higher in patients with GDM and anemia of chronic diseases than in healthy pregnant women or in pregnant women with iron deficiency anemia. An analysis of iron metabolism markers in pregnant women with GDM established that patients with anemia of chronic diseases had higher hepcidin levels than women with iron deficiency anemia or healthy pregnant women.

Conclusions. We established the heterogeneity of the anemic syndrome in pregnancy complicated by GDM. It was confirmed that GDM was accompanied by subclinical inflammation, which was more pronounced in anemia of chronic diseases. The research showed that the mechanism of development of anemia of chronic diseases involving the hepcidin protein was also realized in GDM, characterized by subclinical inflammation. The results indicate the importance of establishing the type of the anemic syndrome in pregnant women with GDM for effective therapeutic follow-up.

The aim was to study the association of the rs6318 polymorphism of the HTR2C gene with the level of depression and quality of life in patients undergoing coronary artery bypass grafting (CABG).

Materials and methods. A total of 116 patients with coronary artery disease (CAD) (age 60 [57; 65] years) were examined before CABG. Depression was assessed in all patients in the preoperative period using the Beck Depression Inventory (BDI). In addition, the quality of life was measured in all patients using the SF-36 questionnaire. Blood samples were collected for the subsequent polymerase chain reaction-based genotyping to detect the rs6318 polymorphism of the HTR2C gene. Statistical analysis was performed using the STATISTICA 10.0 software package (StatSoft Inc., USA). The value of p < 0.05 was considered statistically significant.

Results. No significant differences were found in the associations between different genotypes of the HTR2C gene and depression levels. However, certain trends have been established (p = 0.1). Thus, the pairwise comparison of different genotypes reported that carriers of the CC genotype had higher BDI scores (12 [8; 19]), whereas carriers of the CG genotype (p = 0.07) and GG genotype (p = 0.08) had lower BDI scores (3.5 [2; 5] and 8 [0; 25], respectively). The quality of life among carriers of the CC, CG and GG genotypes did not differ significantly. Nevertheless, the median values of almost all indicators (GH, PF, RE, VT) were lower in carriers of the CC genotype. Carriers of the CC genotype suffered more from pain limiting their daily activities than carriers of the GG genotype (p = 0.04). Homozygous C allele carriers demonstrated poorer mental health than heterozygous carriers (56 [40; 64] vs 82 [72; 92], p = 0.04).

Conclusions. Reliable associations of different genotypes of the rs6318 polymorphism of the HTR2C gene with the quality of life parameters have been found in patients with coronary artery disease.

Aim. To develop a pathogenetically reasonable model of type 2 diabetes with marked peripheral insulin resistance and relative insulin deficiency in rats using a high-fat diet and a single injection of streptozotocin in the low dose.

Materials and methods. Experiments were conducted on 16 outbred male rats. Type 2 diabetes model in experimental animals was achieved by feeding them with high-fat diet (55% of energy from fat) for 28 days followed by a single injection of streptozotocin (35 mg/kg). The serum glucose and insulin concentrations in rats were measured before streptozotocin administration and at the end of the experiment. To estimate insulin resistance, insulin tolerance test and glucose tolerance test were performed. Total protein, albumin, total and direct bilirubin, urea, uric acid, total cholesterol, high-density lipoproteins and low-density lipoproteins, and activity of alanine aminotransferase and aspartate aminotransferase were measured in the blood serum.

Results. A high-fat diet with a single injection of streptozotocin resulted in lipid and protein metabolism disorders and peripheral tissues insulin resistance in experimental animals. Basal insulin levels did not change against the backdrop of high glucose level.

Conclusions. These results indicate that feeding rats with a high-fat diet (55% of calories from fats) and a single administration of streptozotocin at a low dose (35 mg/kg) reproduce general pathological processes of type 2 diabetes. This model can be used to study the pathogenesis of type 2 diabetes as well as to investigate the effect of potential hypoglycemic agents.

Relevance. Human neutrophil antigens (HNAs) are localized on glycoproteins which are positioned on the surface membrane of human neutrophils. Alloantibodies against HNA are implicated in a number of clinical conditions, including immune-mediated neutropenia and transfusion reactions. Genotyping for HNA systems is important in the diagnosis of disorders involving alloimmunization to HNA.

Aim. To assess the risk of HNA alloimmunization in donors and patients with hematological diseases in St. Petersburg based on the study of HNA allele and genotype frequencies.

Materials and methods. DNA samples of 303 blood donors and 302 hematological patients were obtained and typed for HNA-1, -3, -4, -5. Polymerase chain reactions with homemade sequence-specific primers were used for typing. Genomic DNA was isolated from whole blood by a multistage purification method using the CTAB reagent. The results were detected in real time using the EVAGreen intercalating dye. Pearson’s chi-squared test was used to compare the HNA genotype frequencies in donors, patients with hematological diseases and in other populations.

Results. In the study, the frequency of HNA-1bd allele was 0.584–0.588, of HNA-1a – 0.376–0.384, of HNA- 1bc – 0.032–0.036. HNA-1bc allele was represented in the genotypes HNA-1a/bc/bd (0.023–0.036), HNA-1a/bc (0.020–0.043) and HNA-1bc/bd (0.007–0.010). The genotypes HNA-1bc/bc and HNA-1null were not identified. Allele “a” of HNA-3, -4, -5 systems was found in the majority of studied individuals (0.795–0.804; 0.887–0.898; 0.699–0.708). The highest calculated risk of HNA alloimmunization was noted in the absence of HNA-5b, HNA- 1a, HNA-3b, and HNA-4b alleles in the genotype and was 0.250, 0.233, 0.231, and 0.163, respectively.

Conclusions. Our data are consistent with the results of studies on the HNA allele and genotype frequencies in populations of Europeans and are significantly different from those of East and Southeast Asia, Africa and South America. The frequencies of HNA-1, -3, -4, -5 alleles and genotypes among donors in St. Petersburg and patients with hematological diseases did not have statistically significant differences. It was shown that the highest calculated risk of alloimmunization was observed in the absence of HNA-5b, HNA-1a, HNA-3b, and HNA-4b alleles in the genotype. These data are consistent with the results of similar studies on populations of white Europeans conducted by other authors.

 

Aim. To study the surface and cellular composition of non-calcified bioprosthetic heart valve (BHV) leaflets with varying degrees of structural deterioration to determine the possible mechanisms of primary tissue failure development.

Materials and methods. An examination of six bioprosthetic heart valves (KemCor and PeriCor) extracted from mitral position due to the structural valve deterioration was performed. The structure of BHV leaflets was studied by hematoxylin – eosin staining and immunohistochemistry assay (with the following indicators – CD3, T lymphocytes; CD20, B lymphocytes; CD31, mature endothelial cells; CD34, endothelial progenitor cells; CD68, monocytes/macrophages; vimentin, mesenchymal cells; α-smooth muscle actin, vascular smooth muscle cells).

Results. The degree of disruption of BHV leaflets in primary tissue failure differed significantly: relatively intact samples with the intact endothelial monolayer, areas with impairment of the surface layers (minimal and moderate damage) and areas with the spread of destruction into the extracellular matrix of the leaflet (expressed degeneration) were determined. Endothelial cells (monolayer with preserved or impaired integrity), macrophages, smooth muscle cells and other mesenchymal lineage cells were identified in BHV. T- and B-lymphocytes were not detected in the BHV leaflets.

Conclusions. A characteristic feature of structurally deteriorated BHVs is impairment of endothelial monolayer integrity in areas of degraded extracellular matrix. In contrast to other types of bioprosthetic dysfunctions, structural valve deterioration was characterized by the absence of lymphocyte infiltration. Therefore, we suppose that endothelial mololayer injury is a trigger of structural BHV deterioration.

Background. The attention of many researchers is focused on studying the role of adipokines secreted by subcutaneous, visceral, epicardial, and perivascular adipose tissues in the pathogenesis of diseases of the cardiovascular system. At the same time, adipose tissue of retrosternal localization remains out of research focus. This pool of fat cells is formed at the site of the thymic involution and has a significant volume. However, their functional activity and participation in the development of cardiovascular pathology remain unexplored.

Aim. To study the morphological characteristics of adipocytes of the retrosternal adipose tissue (RSAT) and their production of adipokines in comparison with epicardial (EAT) and subcutaneous adipose tissue (SCAT) and to investigate their relationships with arterial stiffness parameters in patients who underwent coronary artery bypass grafting.

Materials and methods. The study included 17 patients (12 men/5 women aged 40–70 years) with the diagnosed coronary artery disease (CAD) who underwent coronary artery bypass grafting (CABG). Each patient underwent measurement of carotid-femoral pulse wave velocity (PWV) and aortic augmentation index (AIx) with the oscillometric device. Isolated adipocytes were obtained enzymatically from explants of SCAT, EAT and RSAT during coronary artery bypass grafting. The adipocytes were analyzed under the microscope at 200x magnification. The release of adiponectin, leptin and insulin was studied in the adipocyte supernatant after 1 hour incubation using ELISA.

Results. It was found that adipocytes of the RSAT are smaller than adipocytes of SCAT: 83.96 ± 2.21 vs 98.62 ± 2.67 μm (p = 0.00002), respectively, and comparable in size to adipocytes of EAT: 86.65 ± 1.33 μm. The release of adiponectin by adipocytes of the RSAT turned out to be comparable to the production of this adipokine in SCAT and EAT, however, adipocytes of the RSAT produce less leptin than SCAT and EAT: 0.26 (0.19; 0.27) ng/l vs 0.37 (0.28; 0.55) (р = 0.01) and vs 0.32 (0.28; 0.44) (р = 0.006) ng/ml, respectively. Furthermore, RSAT produce less insulin than SCAT and EAT: 1.56 (1.03; 2.08) vs 1.70 (0.99; 2.18) ng/ml, (р = 0.0022) and 1.76 (1.16; 2.40) ng/ml (р = 0.006), respectively.
A positive correlation was found between the secretion of leptin by adipocytes of the RSAT and the AIx  (rs = 0.52, p = 0.046). An inverse relationship was found between insulin secretion by retrosternal adipocytes and PWV rs = –0.55, p = 0.035). There was no relationship between the size of the  retrosternal adipocyte or hypertrophy of the thymic adipocytes (more than 100 μm) and the production of leptin and insulin and arterial stiffness parameters. 

Conclusions. The data of our pilot study show that adipocyte hypertrophy of the retrosternal AT is not a significant marker of adipokine production disturbance. The observed relationships suggest that an increase in leptin production and reduced insulin secretion by retrosternal AT may contribute to the formation of adipokine-related arterial stiffness. Based on the data obtained, it can be assumed that adipokines produced by the retrosternal AT can participate in the formation of arterial stiffness in patients with coronary artery disease.  

Relevance. Impairment of apoptosis regulation in P19 cells is correlated with generation of oxidative stress. Under hypoxia, changes in mitochondrial functions occur, which may exacerbate oxidative stress in the tumor cell. The aim of the study was to evaluate the effects of N-ethylmaleimide and 1,4-dithioerythritol on implementation and regulation of apoptosis in P19 cells under hypoxia in vitro.

Materials and methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. For redox status modulation, 5mM N-ethylmaleimide and 1,4-dithioerythritol in the final concentrations of 5 mM were used. The intracellular concentration of calcium ions, the transmembrane potential and the number of Annexin V, CD95 and CD120 positive cells were determined by flow cytometry. The levels of reduced, oxidized and protein-bound glutathione, protein SH groups, hydroxyl radical and protein carbonyl derivatives were measured by spectrophotometry.

Results. The alteration in the redox status of the glutathione system under hypoxia, accompanied by oxidative modification of proteins (glutathionylation and carbonylation), influences the metabolism in the tumor cell on the whole. Under the effects of 1,4-dithioerythritol, an SH group protector, this alteration promotes formation of additional mechanisms to escape apoptosis, whereas under the effects of N-ethylmaleimide, an SH group blocker, it, on the contrary, promotes apoptosis activation.

Conclusions. The changes in the redox homeostasis of the tumor cell and modulation of oxidative modification of proteins (glutathionylation and carbonylation) under hypoxia are one of the promising approaches to targeted regulation of cell death.

The aim was to compare the relationship between the severity of depression symptoms among the unorganized population of Krasnoyarsk in 2006 and 2012 with respect to socioeconomic and demographic factors; and to compare their prevalence for the analyzed period.

Materials and methods. Two sample groups were selected from the unorganized population that resided permanently in the territory of Krasnoyarsk in 2006 and 2012. Evaluation of the severity of depression in both cases was carried out according to the Hospital Anxiety and Depression Scale, Depression subscale (HADS-D). 

Results. In both sample groups, the frequency of depression was associated with age. In 2012, social and economic factors of depression were revealed: lack of higher education, widowhood, unemployment and family poverty. A significant decrease in the frequency of increased (39.1% vs 16.4%) and clinical depression (14.6% vs 4.5%) was found for the period from 2006 to 2012.

 

Conclusions. In 2012, the frequency of the above-normal depression level according to HADS-D in working age population was largely determined by the influence of socioeconomic factors. A decrease in the frequency of increased and clinical levels of depression among the adult population of Krasnoyarsk over the period from 2006 to 2012 was established.

Aim. To optimize a bioengineered I-Wire platform to grow tissue-engineered constructs (TCs) derived from coronary artery smooth muscle cells and characterize the mechano-elastic properties of the grown TCs.

Materials and methods. A fibrinogen-based cell mixture was pipetted in a casting mold having two parallel titanium anchoring wires inserted in the grooves on opposite ends of the mold to support the TC. The casting mold was 3 mm in depth, 2 mm in width and 12 mm in length. To measure TC deformation, a flexible probe with a diameter of 365 mcm and a length of 42 mm was utilized. The deflection of the probe tip at various tensile forces applied to the TC was recorded using an inverted microscope optical recording system. The elasticity modulus was calculated based on a stretch-stress diagram reconstructed for each TC. The mechano-elastic properties of control TCs and TCs under the influence of isoproterenol (Iso), acetylcholine (ACh), blebbistatin (Bb), and cytochalasin D (Cyto-D) were evaluated. Immunohistochemical staining of smooth muscle α-actin, desmin and the cell nucleus
was implemented for the structural characterization of the TCs.

Results. The TCs formed on day 5–6 of incubation. Subsequent measurements during the following 7 days did not reveal significant changes in elasticity. Values of the elastic modulus were 7.4 ± 1.5 kPa on the first day, 7.9 ± 1.4 kPa on the third day, and 7.8 ± 1.9 kPa on the seventh day of culturing after TC formation. Changes in the mechano-elastic properties of the TCs in response to the subsequent application of Bb and Cyto-D had a two-phase pattern, indicating a possibility of determining active and passive elements of the TC elasticity. The application of 1 µM of Iso led to an increase in the value of the elastic modulus from 7.9 ± 1.5 kPa to 10.2 ± 2.1 kPa (p < 0.05, n = 6). ACh did not cause a significant change in elasticity.

Conclusion. The system allows quantification of the mechano-elastic properties of TCs in response to pharmacological stimuli and can be useful to model pathological changes in vascular smooth muscle cells.

Aim. To study the state of the antioxidant system in mitochondria of skin cells during B16/F10 melanoma growth in mice with chronic neurogenic pain.

Materials and methods. The study included female С57ВL/6 mice (n = 28). Experimental groups included an intact group, a control group – chronic neurogenic pain model, a comparison group – standard subcutaneous transplantation of В16/F10 melanoma, and a main group – transplantation of  В16/F10 melanoma 3 weeks after creation of a model of chronic neurogenic pain. Animals were decapitated on day 14 of the В16/F10 melanoma growth, the skin was excised and mitochondria were isolated. Standard ELISA test systems were used to determine the levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) (Bio Source, USA); glutathione peroxidase-4 (GPx 4) (Clod-Clon Corporation, CNDR); glutathione reductase (GR) (Cusabio, CNDR); glutathione S-transferase (G-S-T) (Ivvundiagnostik, Germany); glutathione peroxidase-1 (GPx 1), and superoxide dismutase-2 (SOD-2) (Ab Frontier, South Korea).

Results. Mitochondria of skin cells in controls showed an increase in the levels of GSH by 1.3 times, GPx 1 – by 2.9 times, GPx 4 – by 1.9 times, GR – by 2.8 times, and SOD-2 – by 2.4 times, compared to intact animals. Changes in the comparison group were opposite: GPx 1 decreased by 1.9 times, GPx 4 – by 3.7 times, GR – by 3.9 times, SOD-2 – by 3.8 times, and GSSG rose by 1.36 times compared to intact animals. The growth of melanoma with chronic neurogenic pain caused an increase in the levels of GSH by 1.5 times, GPx 1 – by 3.6 times, G-S-T – by 1.28 times, GPx 4 – by 1.6 times, and SOD-2 – by 1.8 times, compared to intact animals.

Conclusions. The growth of В16/F10 melanoma together with chronic neurogenic pain restructures the antioxidant system of skin mitochondria towards generation of reductive stress under the influence of chronic pain, which can affect the growth and development of experimental melanoma.

Every year, about six million people die from tobacco use. Respiratory epithelium is the first line of defense against exogenous invasion, in particular, harmful inhaled particles, pathogens and allergens. However, the epithelium of the respiratory tract is also a regulator of immunological and inflammatory reactions through secretion of inflammation and immune cell recruitment mediators. An important component of the pulmonary immune system is the surfactant, and, in particular, its proteins SP-A and SP-D, synthesized mainly by type II pneumocytes.

Aim. To assess the levels of surfactant proteins SP-A and SP-D in the blood of smoking patients without bronchopulmonary diseases.

Materials and мethods. The study included 59 patients admitted to the department of internal medicine with hypertension. The general group was divided into subgroups: non-smoking patients (n = 31) and healthy smokers (n = 28). All patients underwent clinical, functional, diagnostic and laboratory tests. The content of surfactant proteins SP-A and SP-D in the blood was determined by enzyme immunoassay.

Results. The subgroups did not differ in sex, age, height, body weight, blood pressure, heart rate, respiratory rate, and the distribution of comorbidities. The subgroups differed in the platelet level; in other main parameters of complete blood count and blood biochemistry no differences were revealed. It was found that the blood levels of surfactant proteins SP-A and SP-D in the subgroup of healthy smokers were significantly higher in comparison with the subgroup of non-smoking patients. The correlation analysis revealed a direct relationship between surfactant proteins SP-A and SP-D and smoking (R = 0.360, p = 0.006, R = 0.274, p = 0.037), a negative correlation between SP-D protein and age (R = –0.315, p = 0.016), and a direct relationship between SP-A protein and diastolic blood pressure (R = 0.271, p = 0.039). In the non-smoking subgroup, a negative correlation between SP-D and age (R = –0.438, p = 0.016) and between SP-D and systolic blood pressure (R = –0.433, p = 0.017) was identified.

Conclusion. The direct relationship between higher levels of the surfactant proteins SP-A and SP-D and smoking in the group of healthy smokers is justified (inflammatory changes, structural abnormalities in the lung parenchyma under the influence of cigarette smoke). The SP-D protein is more significant in comparison with the SP-A protein in vascular wall remodeling, lung tissue matrix, oxidative lung tissue damage, and apoptosis, which explains its negative correlation with age and systolic blood pressure.

Aim. To correlate the concentration of markers of extracellular matrix (ECM) destruction in peripheral blood with morphological characteristics of inflammatory activity and to evaluate their applicability in determining treatment strategy for patients with pulmonary tuberculoma (TUB).

Materials and methods. Peripheral blood samples were taken from 87 patients diagnosed with TUB. The concentrations of matrix metalloproteinases (MMPs), such as collagenases (MMP-1 and MMP-8), stromelysin (MMP-3), gelatinase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1), were measured using the ELISA method (R&D Systems, Minneapolis, MN, USA). The activity of α2-macroglobulin (MG), neutrophil elastase (NE) and proteinase inhibitor (PI) were measured using enzyme assays; acute phase reactants (APR) – haptoglobin (GP) and α1-acid glycoprotein (AGP) – were measured using immunoturbidimetric assays (Thermo Fisher Scientific, USA). Statistica 7 software package and the predictive classification method (PCM) were employed for data analysis.

Results. It has been established that TUB as a clinical form of pulmonary tuberculosis (TB) is characterised by enzyme imbalance between MMP, NE and their inhibitors, namely, by an increase in the levels of MMP-1, MMP-8, MMP-9, and NE and a decrease in MG without changes in MMP-3, TIMP-1 and PI. There is a clear correlation between markers of ECM destruction in blood and morphological characteristics of inflammatory activity. The combinations of MMP-1 and MG can serve as a diagnostic criterion for caseous necrosis in the TUB centre (the alterative component of inflammation), while the levels of MMP-8 and MG can be indicative of granulomatous changes in the capsule (the productive component of inflammation). Various combinations of markers of ECM destruction (with or without APR) enable to predict a particular morphological pattern with accuracy from 80% up to 92%.

Conclusion. When determining a treatment strategy for patients with TUB, biochemical data which allow to assess the tempo and intensity of the inflammation process should be taken into account along with a dataset of clinical and radiological features.

An inflammatory process accompanied by a considerable number of pathological conditions in the body is one of the symptoms of infective endocarditis. The components of the immune system involved in the inflammatory response may serve as markers determining the development and prognosis of the disease and as potential therapeutic targets. These components include cytokines IL-33, sST2, and the IL-33/ST2 system, which are actively involved in the modulation of the inflammatory response. At present, the role of these biologically active molecules is well described for various pathologies associated with tissue destruction, including cardiovascular diseases, but not for the pathogenesis of infective endocarditis. This review is aimed at analyzing the available information on the pathogenesis of infective endocarditis, the role of IL-33 and ST2 in the formation of the inflammatory response in various pathological processes, and changes in the expression of the genes encoding these proteins under the influence of various factors.

Genital gonorrhea is one of the most common sexually transmitted diseases with significant gender differences in its clinical course. Laboratory verification of the diagnosis is associated with great difficulties in the cultivation and identification of the pathogen. Moreover, the diagnosis of female gonorrhea is a serious problem due to mild symptoms of the disease. Currently, a promising trend in the diagnosis of inflammatory diseases of reproductive organs is biochemical analysis of vaginal and sperm fluids, which have a rich component composition. Biogenic polyamines can be synthesized by both pro- and eukaryotic cells. These polycations are present in semen and vaginal fluid and can have a significant effect on various cell structures and functions. In this regard, the qualitative and quantitative composition, the level and ratio of these components and their changes can have a diagnostic value for infections of the genital tract.
The aim of the review was to analyze current information on the role of biogenic polyamines in the physiological and biochemical potential of Neisseria gonorrhoeae and their participation in the development of genital gonococcal infection, taking into account the influence of sexual differences and a number of related factors. Special attention was paid to the origin and possible functional role of polyamines in the genital tract of men and women. As a result, taking into account the spectrum, origin and ratio of polyamines in the corresponding fluids, we formulated a hypothesis: the manifestation of the process in case of infection in men is largely determined by the reactivity of eukaryotic cells, but not the metabolic activity of the microbiota of the reproductive tract. At the same time, the development of “female” gonorrhea is primarily determined by the state of the microbiocenosis of the cervical vaginal biotope.

The review highlights the issue of applying virtual reality (VR) technologies in medical rehabilitation of patients with cerebral palsy (CP). This review generalizes the current evidence on the use of virtual reality in restoration of motor and coordination functions, as well as in correction of other diseases associated with motor disorders in patients with CP. The analysis of national and international research shows that at present it is impossible to speak unambiguously about the efficiency of VR in rehabilitation of patients with CP. This is explained by some methodological shortcomings of the analyzed works (small size of the studied samples, lack of control over the results in the long term). However, the use of VR technologies for improving various functions in patients with CP is a promising method of medical rehabilitation.

In this review, various achievements in the field of development of tissue-engineered scaffolds with the electrospinning approach were observed. Through the appropriate selection of electrospinning parameters, such as solution viscosity, the type of solvent, voltage, the distance between a tip and a collector etc., scaffolds with a high degree of porosity and pore size applicable for optimal cell infiltration can be obtained. These tissue-like materials can be produced from both synthetic and natural polymers and their mixtures. Based on the characteristics specific for the desirable tissue – vascular, bone or cardiac – materials providing the required mechanical properties, architecture, degradation kinetics and biocompatibility are selected for scaffold synthesis. In different studies, electrospun fibers were modified by adding biologically active agents or nanoparticles. This article also describes the particularities of the extracellular matrix of different tissues and approaches used for specific tissue imitation.  Repopulation of the matrices with autologous cells before transplantation is the most commonly used method to improve the biocompatibility of the scaffold and the recipient.

In the last decades, the problem of antibiotic resistance occupies one of the key positions in the global public health system and requires attention from the medical community. Antimicrobial resistance monitoring systems play an important role in tracking the changes in antimicrobial susceptibility for timely correction of antimicrobial therapy. The pharmaceutical industry applies epidemiological data obtained through such monitoring to the creation of new medicines and modification of the antimicrobial substances developed earlier. The article describes some of the international and Russian monitoring systems created at different times. It should be noted that during development, regional-level data are used, while a number of projects present information on a global scale. The completed comparative analysis of available systems revealed both positive aspects and parameters in need of renovation. At the same time, the standardization of collecting basic data for monitoring programs requires significant changes. The majority of systems are able to examine only a limited range of microorganisms and antimicrobials. An important point in the functioning of monitoring systems is a search for the optimal way to visualize output data in tables, interactive maps, and graphics. A significant amount of projects demand further work on the result presentation options. Constant monitoring is a significant component in modern concepts of antibiotic resistance control due to the increasing occurrence of resistant organisms.

Neurogenic inflammation is a pathological process based on bidirectional interactions between cells of the nervous and immune systems as well as on a wide range of biologically active substances.

Aim. Basing on scientific publications and information provided in databases, to analyze markers of neurogenic inflammation (biochemical, genetic) and characterize their involvement in the pathogenesis of diseases of various organ systems.

Results. Neurogenic inflammation that occurs during the development of various diseases (asthma, urticaria, atopic dermatitis, psoriasis, rheumatoid arthritis, pain syndrome, interstitial cystitis, colitis, etc.) is characterized by common stages and pathophysiologically active substances. Mediators released by nerve cells (substance P, calcitonin gene-related peptide, vasoactive peptide), acting on specific receptors, contribute to mast cell degranulation with the release of a complex of biologically active substances (histamine, tryptase, nerve growth factor, etc.), which activate inflammatory processes. Biologically active substances and receptors significant for the development of neurogenic inflammation are under genetic control. At the same time, there are overlaps of the spectrum of diseases for which importance in the pathogenesis of neurogenic inflammation is proved and an association between variants of neurogenic inflammation genes. This makes it possible to conclude that the course of neurogenic inflammation will depend not only on the etiological factors, but also on the genetic features of key molecules involved in neurogenic inflammation processes. The similarity of the pathogenetic links of neurogenic inflammation (at the genetic and biochemical levels) in various pathologies may underlie the formation of comorbid conditions.

Conclusion. Understanding the biochemical and genetic components of the development of neurogenic inflammation is of interest for prevention and treatment of diseases (including comorbid ones) based on this pathological process.  

Cardiovascular diseases retain their leading position among the leading causes of death worldwide. The contribution of many factors to increasing risk of developing cardiovascular diseases was proven. The article provides an overview of current views on the role of risk factors in assessment of cardiovascular risk in asymptomatic patients. Determination of individual cardiovascular risk is not questioned. However, more information is accumulating on the need to supplement the existing cardiovascular risk assessment scales with new factors in order to more accurately predict cardiovascular risk. The value of alternative risk factors, such as psychosocial factor, level of physical activity, family history of cardiovascular diseases, coronary artery calcification, ankle-brachial index, and identification of atherosclerotic plaques during ultrasound scanning of the brachiocephalic arteries, is described. Studies that consider the impact of these risk factors on reducing discrimination against cardiovascular risk when added to the globally used risk assessment scales are presented.

Diabetes mellitus (DM) is associated with changes in the structure of the brain and deterioration of cognitive functions from mild to moderate according to neuropsychological testing. With the growing DM epidemic and the increasing number of people living to old age, cognitive dysfunctions associated with DM can have serious consequences for the future of public and practical health. Chronic hyperglycemia, severe episodes of hypoglycemia, and microvascular complications are important risk factors common for type 1 and type 2 diabetes. DM is also associated with structural and functional changes in the brain, which can be diagnosed by various types of magnetic resonance imaging (MRI) of the brain. In this review, we investigate studies conducted over the past two decades to improve the understanding of how DM effects the brain function and structure. We also describe the changes characteristic of type 1 and type 2 diabetes during standard MRI, functional MRI and proton magnetic-resonance spectroscopy (proton MRS) as well as their features.

Optogenetics is an innovative and fast-growing field of science combining the advances in molecular biology and laser technologies to monitor various biochemical processes in the cell and to control its activity using light. Therefore, this review is devoted to the implementation of the optogenetic approach to diagnosis and treatment of various socially sensitive diseases at the molecular and genetic level. Furthermore, the article considers different methods of delivery and incorporation of genetic constructs encoding transmembrane proteins. New fiber optic technologies used to develop implantable devices for generating and recording signals in excitable tissues are described. Besides, the most state-of-the-art and popular registration methods are considered in the review.

This clinical case demonstrates the difficulty of timely intravital diagnosis of cardiac amyloidosis and the prescription of adequate drug therapy which is associated not only with the limited possibilities of  establishing a correct diagnosis and the absence of specific treatment in most cases, but also with a delay in seeking medical care. Thus, development and improvement of non-invasive screening methods of examination will allow to identify this pathology at earlier stages with a possibility of prescribing effective drugs and performing heart transplantation in some cases.