Aim. To compare the number of insulin+ cells in the liver and exocrine part of the pancreas with the type of  experimental diabetes, blood glycose and glycated hemoglobin (HbA1с) level and with the number of Pdx1+ cells.

Materials and methods. The experiment was carried out on 25 male Wistar rats (weighting (303.0 ± 25.3) g) that were divided into 3 groups: the first group consisted of intact animals, the second had animals with experimental diabetes type 1, and the third with animals with experimental diabetes type 2. Biochemical, immunohistochemical, ELISA methods and statistical analysis were used.

Results. Insulin+ and Pdx1+ cells of rats with experimental diabetes were found in the liver and exocrine part of pancreas. The highest number of insulin+ cells in the liver was detected in type 2 diabetes (T2D). A strong positive correlation between the number of insulin+ cells in the liver and level of glycosylated hemoglobin in theblood was revealed in both type 1 and type 2 diabetes.

Conclusion. Insulin+ cells are detected in the liver and acinar part of pancreas of both intact rats and rats with experimental diabetes. Group with T2D is characterized by the highest number of insulin+ cells in the liver
compared with type 1 diabetes (T1D). The localization of insulin+ cells in the liver changes depending on the  type of diabetes. In T2D insulin+ cells are located in all parts of liver acini, meanwhile in animals with T1D such cells are mainly detected in the periportal area. The expression of Pdx1+ in acinar cells of pancreas and liver cells is likely a mechanism for their reprogramming into insulin+ cells in experimental diabetes mellitus.

Purpose. The study is focused on development of high-fat, high-carbohydrate diet-induced experimental model of metabolic syndrome (MS) in rats.

Materials and methods. The 6-week old Wistar rats (n = 20) were used for study. Rats were separated into control and experimental groups. The rats from the control group were fed standard rat chow. The rats from the experimental group had a high-fat, high-carbohydrate diet rich in lard (17%) and fructose (17%) and  drank 20% fructose solution. At the end of the study, body weight and blood pressure (BP) were assessed. After 12 weeks of a diet load, an oral glucose tolerance test (GTT) and insulin tolerance test (ITT) were carried out. Lipid and protein biochemical parameters in plasma were analyzed. Adipose tissue and liver were measured at the end of the study. The levels of triacylglycerol (TAG) and cholesterol (Сh) in the liver were determined by enzymatic methods.

Results. High-fat, high-carbohydrate diet feeding in rats for 12 weeks led to BP elevation and increase in the adipose tissue/body weight ratio. Hyperglycemia, impaired glucose tolerance and insulin resistance were found in rats with MS by means of GTT and ITT. Elevation of plasma TAG level was observed in the experimental group, although plasma total Сh and HDL-Ch did not differ from those of controls. Liver/body weight ratio and the level of TAG and Ch in the liver were elevated in rats with MS.

Conclusion. Experimental rat model of diet-induced MS reproduces many aspects of MS in humans. This model may be useful for studying the pathophysiology of MS and methods for its prevention and treatment.

Purpose. To evaluate the potential option of selecting donor–recipient pairs by using the number of epitope
mismatches.

Materials and methods. An observational cohort study was carried out, which included 824 adult recipients of ABO compatible deceased donor kidneys. The end point was a transplant loss. If a recipient with a functioning graft died, the observation was censored. The number of epitope mismatches (EpMM) was calculated using open source information on the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. After that, the number of donor epitopes absent in the recipient was calculated for each combination with a non-zero probability, whereupon the weighted mean EpMM was calculated, where the weight coefficient was the normalized probability of occurrence of each combination.

Results. All of the donor – recipient pairs had HLA-mismatches (HLA MM): 1.9% of recipients had 1 HLA MM, 6.7% had 2 HLA MM, 29.9% had 3 HLA MM, 38.5% had 4 HLA MM, 18.1% had 5 HLA MM, and 4.9% had 6 HLA MM. The HLA MM impacted graft survival was determined: log-rank test p < 0.0001, Breslow test p < 0.0001. The median values and the interquartile ranges of EpMM were 6 [4; 7], 12 [7.74; 17.25], 18 [14; 22], 24 [20; 30], 30.5 [25; 37] and 36 [26.5; 44.5] for the cases of 1, 2, 3, 4, 5 and 6 HLA MMs, respectively. An increase in HLA MM resulted in a higher risk of developing donor-specific anti-HLA antibodies (DSA). Hazard ratio (HR) = 1.21 [95% confidence interval (CI): 0.7; 1.9], 1.71 [95% CI: 1.22; 2.36], 2.04 [95% CI: 1.42; 2.73], 2.25 [95% CI: 1.63; 2.96], 2.59 [95% CI: 2.03; 3.29] for 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also resulted in a higher risk of developing DSA. HR = 1.66 [95% CI: 1.09; 2.47], 2.1 [95% CI: 1.46; 2.91], 2.41 [95% CI: 1.86; 3.03], 2.61 [95% CI: 2.12; 3.12], 2.77 [95% CI: 2.26; 3.33] for 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. An increase in HLA MM was associated with an increased risk of transplant loss. HR = 1.24 [95% CI 0.7; 2.15], 1.48 [95% CI 0.86; 2.33], 1.88 [95% CI 1.32; 2.52], 2.41 [95% CI 2; 2.93], 2, 98 [95% CI 2.59; 3.46] at 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also was associated with an increased risk of transplant loss. HR = 1.71 [95% CI 1.1; 2.49], 2.11 [95% CI 1.59; 2.68], 2.4 [95% CI 1.96; 2.86], 2.59 [95% CI 2.17; 3.04], 2.71 [95% CI 2.31; 3.15] at 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. In order to demonstrate the effectiveness of EpMM accounting, we analyzed graft survival  among the patients with 4 HLA MM. With the number of EpMM in the range from 10 to 24 and from 25 to 43  the difference in survival rates was statistically significant, but only at the late stages of the post-transplant  period: log-rank test p = 0.0067, Breslow test p = 0.0982. The median survival for EpMM 10–24 was 10.33  [95% CI 9.05; 11.61] years, for EpMM 22–43 – 8.67 [95% CI 7.68; 9.66] years, HR 1537 [95% CI 1.114;  2.12]. At the same time, it was not the median of survival that increased, but the proportion of patients with a functioning graft: at 10-24 EpMM after 15 years, 18.28% [95% CI 8.2; 31.67] grafts functioned, while at 25–43 EpMM only 4.75% [95% CI 0.94; 13.64] functioned.

Conclusion. In the routine practice of a transplantation center with a short waiting list of its own, it might be possible to improve the kidney transplant survival as a result of considering epitope mismatches, thus  reducing the risk of developing donor-specific anti-HLA antibodies and ensuring a higher graft survival rate. This method can be used for additional ranking of transplantation candidates depending on the number of epitope mismatches within the fixed number of HLA-mismatches and thus select the optimal one. Besides, it is theoretically possible to use this method as an alternative to the traditional donor/recipient histocompatibility evaluation. Additional research is required.

Background. The identification of predictive molecular markers of luminal breast cancer will help to assess the risk of developing distant metastases and determine a personalized approach to predicting the outcome of the disease during hormone therapy.

The aim of the study was to investigate the relationship between the transcription factors GATA3, FOXA1, and ELF5 in the tumor and the occurrence of distant metastases in patients with luminal subtype of breast cancer during adjuvant hormone therapy.

Materials and methods. The study included 101 patients with breast cancer (aged from 30 years to 81 years, average age (54.8 ± 10.3) years), with stages T1–4N1–3M0 of the disease. The follow-up period was at least 5 years. The inclusion criteria for the study were luminal molecular genetic subtype of the tumor and lack of preoperative treatment. The exclusion criterion was stage IV disease. The study of transcription factors was carried out by the immunohistochemical method using polyclonal antibodies to GATA3, FOXA1, and ELF5, manufactured by Flarebio (Austria).

Results. Low expression of FOXA1 and ELF5 in the tumor was associated with the development of distant metastases (p = 0.000015 and p = 0.000002, respectively). In addition, it was found that high incidence of hematogenous metastases was associated with heterogeneous expression of FOXA1 (χ2 = 6.42; p = 0.01) and ELF5 (χ2 = 14.46; p = 0.0001) in the tumor. No similar differences were found in the study of GATA3 expression.

Conclusion. The level of expression of transcription factors FOXA1 and ELF5 and their distribution in the primary tumor can be considered as potential molecular markers in assessing the risk of hematogenous metastasis in patients with luminal breast cancer.

Objective. To study neurophysiological correlates of inhibitory control to determine the features of inhibition
processes in alcohol dependence.

Materials and methods. 77 patients with alcohol dependence were examined (42 men and 35 women) (F10.
2 according to ICD-10). Patients were examined using a test to assess inhibitory control – Go/No – go. According to the task performance, patients were divided into two groups: group 1 – without inhibitory control impairments, group 2 – with impaired inhibitory control. During execution of test, electroencephalogram recordings were made according to the 10–20 system. The values of spectral power and coherence of θ-, α- and β-rhythms were analyzed. Statistical processing was carried out using nonparametric Mann–Whitney U-test and Wilcoxon W-test.

Results. In patients with impaired inhibitory control, there was a decrease in the spectral power of the α-rhythm in the frontal cortex (p = 0.003), whereas in patients without inhibitory control disorders – in the Central cortex (p = 0.036). Patients with impaired inhibitory control responded by increasing β-power to cognitive stimulus in the occipital (p = 0.014), left temporal (p = 0.009) and right temporal (p = 0.008) cortex, while patients without inhibitory control disorders showed an increase in β-power only in the occipital (p = 0.007) and left temporal (p = 0.002) cortex. According to coherence data, patients with impaired inhibitory control have greater involvement of brain structures during the “Go/No – go” test in all frequency ranges.

Conclusions. Patients with and without impaired inhibitory control have regional differences in changes in brain bioelectric activity during the “Go/No – go” test.

The aim was to study the molecular mechanisms of the violation of the structural and functional integrity of
the blood-brain barrier in chronic neurodegeneration of the Alzheimer’s type associated with the development of cerebral angiopathy.

Materials and methods. The transgenic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon,
PSEN1 * M146L * L286V) 6799Vas group which includes 9 months aged males. The control group included C57BL / 6 x SJL mice, males aged 9 months.

Results. The total length of the vessels in the area of the dentate gyrus is 2.5 times greater in transgenic animal models of Alzheimer’s disease than in animals of the control group (p < 0.01). The average diameter of blood vessels in all areas of the hippocampus is smaller compared with the control (p < 0.05). Transgenic modeling of neurodegeneration in the CA2 zone of the hippocampus increases the relative area of tissue with increased permeability of blood-brain barrier (BBB) (17.80 [9.15; 36.75]) compared to control (1.38 [0.04; 7.60]) at p < 0.05. A similar difference (p < 0.05) is also observed in the hippocampal area CA1. A tendency (p > 0.05) to decrease the number of CD31+ endothelial cells in the dentate gyrus of the hippocampus (21.52 [17.56; 24.50]) in animals of the experimental group compared with the control group (23.08[21.18; 29.84]) was detected. A similar situation is observed in the CA2 and CA3 areas of the hippocampus.

Conclusion. Neurodegenerative changes in the hippocampus of animals with a transgenic AD model are associated with impaired microcirculation in the brain tissue as a result of a reduction in the diameter and branching of blood vessels, and damage and increased permeability of BBB.

Aim. To study the levels of reduced and oxidized glutathione (GSH and GSSG, respectively), as well as the thiol status in gastric cancer (GC) tumors of various histological types and grades.

Materials and methods. The indicators were determined by ELISA methods in tumor, peritumoral and visually intact tissues obtained during surgery from 52 patients with GC: 18 patients had a G1-2 adenocarcinoma (AC), 8 with G3 AC, 6 with signet ring cell cancer (SRCC), 14 with combined gastric lesions (CGL) – AC with signet ring cell fragments, 6 with patients with a component of undifferentiated cancer, G4.

Results. In the groups of patients with low-differentiated and undifferentiated tumors, the GSH content in the tumor tissue and the peritumoral zone was higher than in the group of patients with well- and moderately-differentiated tumors. Tumor GSH levels in G3 AC and SRCC exceeded the values in visually intact tissues. Moreover, in the visually intact tissue of patients with SRCC, GSH level was reduced relative to G1-2 AC and CGL. GSH in all tissues of patients with CGL was higher than in patients with G1-2 AC. The lowest level of GSSG in the tumor tissue was registered in SRCC: 27.5% lower than in G1-2 AC and 30.3% lower than in G3 AC. Patients with undifferentiated tumors (G4 AC) had the highest GSH content in all studied tissues: by 29.9% in tumor; by 40.7% in peritumoral zone; and in visually intact tissue not only GSH, but also GSSG was increased by 22.5–25.5% in comparison with AC G1-2. G4 AC was also characterized by a sharp increase in the thiol status in tumor tissues by 80.2 and 89.9% higher than in visually intact and peritumoral tissues, and it was statistically higher than in AC G1-2, AC G3, SRCC and CGL. The ratio of GSH and GSSG was the most informative.

Conclusion. Poor AC differentiation (in the row G1-2, G3, G4) and a change of histological tumor type (AC, SPL and SRCC), i.e. an increase in tumor aggressiveness, were accompanied by the enhancement of reductive processes in tumor tissue, as evidenced by the statistically significant increase in the GSH/GSSG coefficient and a sharp increase in the thiol status in G4 AC.

Aim. To study the ventilation function of the lungs in patients with varying degrees of severity of chronic obstructive pulmonary disease (COPD) and in patients with COPD combined with lung cancer (LC), as well as to establish the features of its disorders using spirography and body plethysmography.

Materials and methods. A clinical and functional study of 57 individuals was carried out with 10 healthy patients (control group), 30 patients with COPD and 17 patients in whom LC was combined with COPD using the Masterlab Pro diagnostic complex (Erich Jaeger, Germany).

Results. In patients with early COPD, a decrease in MEF75 (a ventilation parameter characterizing small airway patency) is the most informative. With the progression of bronchial obstruction, both restrictive and obstructive disorders, characterized by a decrease in FEV1, VC, a change in the structure of the total lung capacity in the form of an increase in the RV/TLC ratio such as an increase in the RV/TLC ratio and an increase in bronchial resistance were recorded. In patients with LC and mild COPD, pulmonary volumes, capacities, flow-volume loop and bronchial resistance parameters did not differ from patients with COPD with a similar bronchial obstruction. In patients with LC and more severe COPD, in contrast to patients suffering from a similar severity of COPD, a decrease in the patency of large, medium and small diameter bronchi (PEF, MEF25, MEF50, MEF75) was detected, which indicated development of generalized bronchial obstruction.

Conclusion. Modern diagnostics of pulmonary ventilation disorders in patients with LC and COPD should be aimed at identifying the disease, and drug therapy should target maximum leveling of reversible components of bronchial obstruction in order to increase the functional reserve of the respiratory system and reduce the risk of postoperative complications caused by COPD.

Background. Chemotherapy is one of the main types of treatment in ovarian cancer. Standard first-line treatment includes platinum drugs. Every fifth patient develops chemoresistance after platinum-containing first line therapy. Glutathione detoxification systems play an important role in platinum drugs utilization.

Purpose. To assess the redox status of blood plasma and ascitic fluid in ovarian cancer patients before and after neoadjuvant platinum-containing chemotherapy (NACT).

Materials and methods. We determined the activity of the glutathione system and thioredoxin levels in blood
plasma before and after NACT and in the ascitic fluid before NACT, and the presence of GSTP1 gene polymorphism (Ile105Val (rs1695), Ala114Val (rs1138272) in 30 III–IV FIGO stage ovarian cancer patients. Patients were divided into 3 groups: NR – no relapse in 2 years after last chemotherapy course; R1 – relapse in less than 6 months; R2 – relapse in more than 6 months.

Results. We established an increase of the glutathione-transferase activity and a decrease of the GSH level in
plasma after chemotherapy in R1 patients, and an opposite dynamic of glutathione-transferase and GSH in the R2 group. Thioredoxin level in plasma of all patients was lower than in the control group; differences in levels between groups were not statistically significant. GSTP1 105Val allele was more frequently present in patients than in the control group, and more frequently in R2 than in R1.

Conclusion. The increase in plasma glutathione-transferase and glutathione-reductase levels can be a prognostic marker of early relapse. Thioredoxine dynamics do not correlate with the chemotherapy response. The presence of the GSTP1 105Val allele is a risk factor for ovarian cancer development, but a protective factor against early relapse.

Background. Mirtazapine is used to treat patients with depressive disorders. A large proportion of patients in this group do not adequately respond to mirtazapine therapy, while many develop undesirable drug reactions of type A. According to the previous studies, P-gp is involved in the biotransformation of mirtazapine, the activity of which is highly dependent on the polymorphism of the gene encoding it.

Aim. The aim of our study was to study the effect of mirtazapine gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders, comorbid with alcohol dependence.

Materials and methods. The study included 119 male patients with depressive disorders, comorbid with alcohol dependence (age 38.7 ± 16.0 years). As a therapy, mirtazapine was used at a dose of 37.8 ± 13.8 mg / day. Evaluation of the effectiveness profile was carried out using psychometric scales. The safety profile was evaluated using the UKU Side-Effect Rating Scale. Genotyping was carried out by polymerase chain reaction in real time.

Results. In the course of the study, results statistically significant in terms of evaluating efficacy and safety were not obtained (HAMD scores at the end of the course of therapy: (CC) 2.5 [2.0; 4.0], (CT) 2.0 [ 1.0; 3.0] and (TT) 2.0 [1.0; 3.0], p > 0.999; according to the UKU scale: (CC) 3.0 [2.8; 3.0], ( CT) 3.0 [3.0; 3.0] and (TT) 3.0 [3.0; 3.0], p > 0.999).

Conclusion. The study of 119 patients with depressive disorders comorbid with alcohol dependence showed that 3435C> T polymorphism of the ABCB1 gene (rs1045642) does not affect the clinical efficacy and safety of mirtazapine.

Aim. A study of the association of the methylation of the promoter of the ABCA1 gene with sudden cardiac death
(SCD).

Materials and methods. The study design is based on the case-control principle. The SCD group included 150 men (mean age (46.7 ± 9.2) years) who died of sudden cardiac death according to forensic medical examination data (the main pathological diagnoses are acute circulatory failure, acute coronary insufficiency). The control group included 150 men (mean age (42.6 ± 1.2) years) who died suddenly, but not due to cardiovascular pathology. DNA was isolated by phenol-chloroform extraction from myocardial tissue. The methylation status of the ABCA1 gene promoter was assessed by methyl-specific polymerase chain reaction. The results obtained were statistically processed in SPSS 16.0 using Pearson’s test and Fisher’s test with Yates’ correction for continuity. P < 0.05 was used as a level of significance.

Results. Comparing the groups revealed statistically significant differences in the methylation status of the gene promoter (p = 0.015). In the SCD group, the proportion of individuals whose ABCA1 gene promoter is methylated is statistically significantly higher compared to the control group (p = 0.020; OR = 5.86; 95% CI (1.28–26.89)).

Conclusion. Methylation of the promoter of the ABCA1 gene is associated with sudden cardiac death.

Purpose. To evaluate the role of thiol status and its correlative relationship with the level of nitric oxide metabolites and vascular endothelial growth factor A (VEGF-A) in the blood plasma of patients with critical lower limb ischemia (CLI) after autovenous reconstructions of femoropopliteal segment’s arteries in the setting of venous endothelium of the arterial bed.

Materials and methods. 54 patients with critical lower limb ischemia had been examined and divided into groups: synthetic prosthesis, in situ autovenous bypass procedure and reversed vein autovenous bypass  procedure. Peripheral venous blood was taken on the 1st and 10th days, and in 1, 3 and 6 months after the operation. Nitric oxide metabolites level was examined with photocolorimetric method by reaction with Griess reagent on a microplate analyzer (Awareness Technology, USA). VEGF-A number estimation was done by ELISA test (PersonalLab, Italy) with the use of Human VEGF-A Platinum ELISA. The level of thiol (SH-) groups was estimated with the use of Ellman’s reagent (SERVA, Germany) on spectrophotometer (Saint-Petersburg, Russian Federation).

Results. The concentration of VEGF-A and the level of SH-groups increase on the 10th day and after 1 month in the group of patients operated on using a synthetic prosthesis. The level of NO metabolites, the concentration of VEGF-A, and the content of SH-groups increase statistically significantly and then decrease to the initial values in the group of patients operated on by reversed vein autovenous bypass procedure. In the group of patients operated on by the in situ method, the level of nitric oxide metabolites increases, the concentration of VEGF-A increases on the 10th day, the level of SH-groups increases, and a positive correlation was found between the content of SHgroups and the concentration of VEGF-A. 

Conclusion. NO metabolites contribute to the build-up of SH groups and VEGF-A in patients operated by the “reversed vein” method, and in patients in the in situ group, the concentration of VEGF-A and the level of  SH groups are not affected, which may be of clinical importance when prescribing NO donors. The revealed patterns of change in the level of recovered thiols, nitrogen oxide metabolites, VEGF-A in combination with analysis of early and late postoperative complications make it possible to conclude the advantage of  autovenous reconstruction of the femoropopliteal segment due to functional adaptation of the venous endothelium compared to the group of patients, operated on by the method of “synthetic prosthesis”. Method in situ on biochemical and angiological indicators proved to be more favorable in terms of the clinical course, than the “reversed vein” method. 

Aim. Studying the influence of the features of aminergic brain status on the development of B16/F10 melanoma in mice with urokinase gene knockout and chronic neurogenic pain (CNP).

Material and methods. The study included female (n = 68) С57ВL/6 mice with the normal urokinase gene (+uPA) and C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice with urokinase gene knockout (–uPA). The model of CNP was created in the animals, and in 14 days B16/F10 melanoma was transplanted. The mice were euthanized 21 days after the transplantation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine (H), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA) were determined in the brain using standard ELISA test systems (Cusabio, China).

Results. CNP in (+uPA) females resulted in the reduction of almost all studied biogenic amines (BA). On the opposite, (–uPA) females showed an increase in NA, DA, 5HT and a decrease of H. 5HIAA increased in both CNP and gene knockout. 5HT in (+uPA) females with CNP decreased, while its physiological level in gene knockout mice was maintained. After 3 weeks of tumor growth in animals with CNP, (+uPA) mice demonstrated increased levels of studied BA (except for 5HIAA) compared to mice with CNP alone. Only H increase was observed in (–uPA) mice from the similar group.

Conclusion. CNP in mice inhibited A-, NA-, H- and 5HT-ergic systems of the brain; the opposite effects were registered in urokinase gene knockout, except for the H-ergic system. Combination of CNP and melanoma in (+uPA) female mice activated all studied BA systems, and in (–uPA) females – H-ergic system only. Different stressful effects, CNP, and genetic disorders (urokinase gene knockout) contributed to changes in the brain BA system functions, leading to the activation of pro- or antitumor mechanisms.

Aim. To assess the variability of the NAT2 gene and to comparatively analyze the prevalence of NAT2 polymorphisms and acetylation types among Yakut and Russian patients newly diagnosed with pulmonary tuberculosis (TB), permanently residing in the Sakha Republic (Yakutia).

Materials and methods. The study included 197 patients with newly diagnosed pulmonary TB (132 Yakuts and 65 Russians) aged (43.3 ± 14.4). The following single-nucleotide polymorphisms were analyzed, using real-time polymerase chain reaction (PCR): NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A),  NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), and NAT2*13 (rs1041983, C282T). Genetically determined basal metabolic rates were calculated using the NATpred online tool.

Results. 75% of residents, both of Yakut and Russian ethnicity, were identified as carriers of NAT2 polymorphic variants known to be related to isoniazid biotransformation. NAT2*6 and *13 allelic variants were more frequent in  Yakuts (occurring in 40.9% and 64.4%, respectively); variants NAT2*5, *6, *11, *12, and *13 were more common in Russians (69.2; 55.4; 67.7; 69.2, and 64.6%, respectively). The NAT2*5, *7, *11, and *12 polymorphisms were found to be significantly ethnicity-dependent. The study established substantial prevalence of medium acetylation type (58.3%) in Yakuts and slow acetylation type in Russians (61.5%). Correlations were shown between ethnicity and different prevalence rates of rapid, medium, or slow acetylation types among patients with TB.

Conclusion. The observed NAT2 polymorphism distribution patterns and isoniazid acetylation types among Yakut and Russian patients with newly diagnosed pulmonary TB demonstrated that pharmacologic  responses can be significantly different between ethnic groups. Findings of pharmacogenetic studies in Yakut and Russian populations should be incorporated in clinical practice for personalized administration of isoniazid.

The aim of this study was to assess the analgesic action of thiowurtzine in somatogenic nociception models by activation of TRPA1 and TRPV1 ion channels.

Materials and methods. The object of the study is the compound 4-(3,4-dibromothiophenecarbonyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo [5.5.0.03,11.05,9]dodecane (thiowurtzine). The analgesic activity of thiowurtzine was studied under the conditions of a chemogenic activation model of TRPA1 channels (by the formalin test), and by a selective test with an agonist of TRPV1 channels (the capsaicin test). The compound was administered once per os in a dose range of 50–200 mg/kg (water-tween solvent) an hour before the experimental manipulations. The reference drugs were diclofenac sodium in a preventive single per os dose of 10 mg/kg in 1% starch gel in a volume of 0.2 ml/mouse, and ketorolac in a dose of 6 mg/kg in the same solvent, volume and route of administration.

Results. Thiowurtzine, when administered in per os doses of 100 and 200 mg/kg, was found to effectively block nociceptive reactions caused by activation of TRPA1 and TRPV1 ion channels. At the same time, the analgesic activity of thiowurtzine turned out to be comparable and/(or) superior to the ketorolac and diclofenac action, depending on the model situation. In addition, it was found that thiowurtzine (200 mg/kg per os) corresponds to diclofenac sodium (10 mg/kg per os) and is superior to ketorolac (6 mg/kg per os) in terms of anti-inflammatory severity in the formalin test.

Conclusion. The biphasicity of behavioral reactions in the prognostic formalin test do not allow for an unambiguous conclusion about the direction of the action mechanism of thiowurtzine, which confirms the polymodality hypothesis. The data obtained in the two models of somatogenic nociception do not exclude the fact that the modulation of the TRPA1 and TRPV1 activity is one of the mechanisms of the thiowurtzine analgesic action. By the key analgesic characteristics found herein, thiowurtzine proves to be a unique compound with a high therapeutic and innovation potential.

The aim is to study the basic physico-mechanical properties of hydroxyapatite (HA) composites (up to 25–50 wt%) with polylactide (PLA-HA) and poly(e-caprolactone) (PCL-HA) prepared by melt compounding, as well as the osteogenic potential of PLA-HA in vivo.

Materials and methods. All biodegradable polymer composites were prepared by hot melt compounding and studied by dielectric spectroscopy in frequency domain, optical microscopy, X-ray diffraction analysis and tensile tests. An ability of PLA-5 wt% HA composites prepared by 3D-printing to induce bone tissue growth in vivo was detected with the help of ectopic subcutaneous test in inbred mice.

Results. Values of the real part of complex permittivity of PLA-HA and PCL-HA composites are increased by 15–30% compared to those for initial PLA and PCL, while tand loss factor does not exceed 0.02 for PLA-based composites and 0.2 for PCL-based composites. The crystallinity degree of PLA-HA composites is increased by 3 and 6 times with an increase of HA content from 25 to 50 wt% respectively compared to the indicator for PLA. The crystallinity degree of PCL-HA composites with 25 wt% HA is increased by 2 times compared to the value for PCL. It is due to the fact that HA powder particles play the role of additional nucleation centers. For all this, mechanical strength of composites diminished statistically. Even lowest HA  content (5 wt%) in PLA-HA composites prepared by 3D-printing increased the incidence of ectopic osteogenesis by 40%.

Conclusion. Designed biodegradable composites have a potential of practical use for bone tissue engineering.

The aim. To evaluate the association of fibrinogen (FGB), tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), lipoprotein lipase (LPL), platelet glycoprotein (ITGB3), and transforming growth factor β (TGFB1) genes  with the incidence of recurrent myocardial infarction (MI) in patients living in the middle Volga region.

Materials and methods. The study included 104 people with recurrent MI compared to 280 people who had just one episode of MI. TNFα (rs1800629), IL1B (rs16944), TGFB1b (rs1800469), FGB (rs1800788), ITGB3 (rs5918) and LPL (rs328) gene polymorphism was determined in all patients using competing TaqMan probes. Association estimation was performed with multivariate logistic regression analysis.

Results. Patients with recurrent MI much more often had TNFα, IL1B, TGFB1b, FGB, ITGB3 and LPL allele and 
genotype polymorphism. Moreover the risk of MI increased significantly in a case of combination of FGB (alleles and genotypes) and TNFα (alleles and genotypes) gene polymorphisms (OR = 4.04, 95% CI = (1.895–8.615), p = 0.0001).

Conclusion. Thus, FGB, LPL, TNFα, TGFB1b and ITGB3 gene polymorphism are associated with more severe 
coronary heart disease and may be a risk factor of recurrent MI development. The dominant total contribution of the FGB (rs1800788) and TNFα (rs1800629) polymorphic genes to the development of recurrent MI in the population of the middle Volga region was revealed.

The aim of the study was to investigate the involvement of bradykinin, cannabinoid and vanilloid (TRPV1 channel) receptors in the implementation of the infarct-limiting effect of chronic normobaric hypoxia (CNH).

Materials and methods. The study was performed on male Wistar rats (n = 117) weighing 250–300 g. Adaptation to CNH was modeled for 21 days at 12% pO2, 0.3% pCO2 and normal atmospheric pressure. A day after adaptation of rats to CNH coronary artery occlusion (45 min) and reperfusion (2 h) was performed. In the study the following compounds were used: selective cannabinoid CB1 receptor antagonist rimonabant (1 mg/kg), selective cannabinoid CB2 receptor antagonist AM630 (2.5 mg/kg), selective bradykinin B2 receptor antagonist HOE140 (50 μg/kg), and vanilloid receptor (TRPV1 channel) antagonist capsazepine (3 mg/kg). All antagonists were administered 15 min before coronary artery occlusion.

Results. Adaptation to normobaric hypoxia promoted the formation of the pronounced infarct-limiting effect.
The blockade of B2 receptor eliminated the infarct-limiting effect of CNH. Blockade of cannabinoid or vanilloid
receptors did not affect the infarct-limiting effect of CNH.

Conclusion. The infarct-limiting effect of CNH depends on the activation of B2 receptor, and the adaptive increase in cardiac tolerance to ischemia/reperfusion does not depend on cannabinoid or vanilloid receptors.

The aim of the study was to develop a method for the modification of human monocytes/macrophages by iron oxide magnetic nanoparticles in vitro.

Materials and methods. Iron oxide magnetic nanoparticles were obtained by a co-precipitation method and coated with a thin SiO2 layer and polyethylene glycol 3000. Murine macrophage-like cell line RAW 264.7, primary human monocytes and macrophages were incubated with magnetic nanoparticles for 1–24 hours. The efficiency of cellular uptake of nanoparticles was measured using a ferrozine-based method and microcopy with Perls’ Prussian blue staining. The cell viability was tested by fluorescent flow cytometry using SYTOX Green.

Results. Incubation of RAW264.7 cell, human monocytes and macrophages with magnetic nanoparticles at a concentration ˃ 5 µg/mL on a rotator for 1 hour at 37 °С provides the loading of nanoparticles into > 99% of cells. The magnetic nanoparticles have no adverse effect on the cell viability. The RAW264.7 cells modified with nanoparticles showed no change in migration activity. The efficiency of the nanoparticle uptake by  macrophages was ˃50 pkg (Fe)/cell.

Conclusion. According to the proposed method, macrophages loaded with magnetic nanoparticles have proved viable, they retain the ability to migrate, and therefore can be used as cell-based delivery systems for tumor diagnostic and therapy.

The aim of the study was to evaluate the gastroprotective effect of dry extracts from the roots and rhizomes of Ferulopsis hystrix in ethanol-induced gastropathy.

Materials and methods. The studies were carried out on 68 white Wistar rats. Ethanol-induced gastropathy was simulated by a single intragastric administration of ethanol in the dose of 10 ml/kg. Animals of the experimental groups received medicinal forms from the roots and rhizomes of F. hystrix: I – decoction in a volume of 10 ml/kg; II–V – dry extracts in the dose of 200 mg/kg, obtained by extraction with purified water, 30, 40 and 70% ethanol, respectively; VI – dry extract, prepared by double extraction with 40% and single extraction with 30% ethanol for 7 days before the modeling of gastropathy. Number of structural changes was determined in the gastric mucosa. They were differentiated into small, large, and strip-like erosions. The Pauls’ index was calculated for structural changes. Pathomorphological studies of the stomach were carried out.

Results. The total number of structural changes in the stomach of animals in experimental groups I, II, IV and V is 44% lower on average, in experimental group III it is 67% lower and in experimental group VI it is 3.6 times lower than in the control. The Pauls’ index for large erosions in experimental groups I–V is 38–75% lower, in experimental group VI it is 83% lower than the index in the control animals. No strip-like erosions are detected in animals of experimental groups III–VI. Pauls’ index for these destructions in experimental groups I and II is 7.0 and 6.5 times lower than the index in the control animals. Microscopic morphological examination registered the increase of shallow-like erosions in the stomach of animals of experimental groups. Shallow-like erosions do not reach the muscularis mucosae. Microcirculation disorders and leukocyte infiltration are less pronounced than in the control group.

Conclusion. F. hystrix has the gastroprotective effect, increasing the resistance of the gastric mucosa to the effect of ethanol. The F. hystrix extract prepared with 30% and 40% ethanol shows the most pronounced pharmacotherapeutic effect in ethanol-induced gastropathy.

Background. Recent studies demonstrated immunosuppressive properties of vascular endothelial growth factor (VEGF-A) and identified VEGF-A as a key mediator of tumor-induced immunosuppression. Placental growth factor (PlGF) is another member of VEGF family in which dramatic elevation is associated with effective immune adaptation in successful pregnancy, whereas low concentrations are related to pregnancy complications resulting from the activation of immune system. Previously, we have shown that activated T cells express VEGF receptor type 1 (VEGFR-1), and PlGF inhibits T cell proliferation in VEGFR-1–dependent manner.

The aim of the present study was to further characterize PlGF effects on T cell responses in vitro.

Materials and methods. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with anti-CD3 monoclonal antibodies (a-CD3) in the absence or presence of PlGF and assessed for IL-10 production, programmed cell death and the expression of inhibitory receptors (PD-1, CTLA-4, Tim-3) in CD4+ and CD8+ T cell subsets.

Results. The addition of PlGF to PBMC cultures activated with a-CD3 resulted in increased percentages of IL- 10-producing CD4+ and CD8+ T cells. Besides, PlGF promoted CD8+ T cells apoptosis while did not affect programmed cell death within CD4+ T cells. Notable, T cell activation with a-CD3 in the presence of PlGF was accompanied by the enhancement of PD-1-expressing cells in CD8+ T cell subset and Tim-3-expressing cells in both CD4+ and CD8+ T cells, and by the increased expression of PD-1 and Tim-3 on T cells.

Conclusion. Our in vitro findings indicate that PlGF can inhibit T cell responses due to the increasing interleukin-10 (IL-10) production, promoting CD8+ T cell apoptosis and enhancing the expression of PD-1 and Tim-3 inhibitory receptors. Given the elevated levels of PlGF in successful pregnancy and its decrease in gestation complications, the obtained data also suggest that PlGF-mediated suppression may be implicated into the governing immune evasion in pregnancy.

Autoimmune bullous dermatosis (ABD) is a group of inherited and acquired skin diseases, the main morphological elements of which are the bullas, developed as a result of autoantibody production directed against protein structures of the epidermis and dermo-epidermal junction, leading to epidermal detachment and blistering on the skin and mucous membranes.

The aim of the research is to analyze the detection rate and structure of polymorbid pathology in patients with autoimmune bullous dermatoses and to determine the Charlson index and 10-year viability in patients before and after prescription of glucocorticosteroid therapy.

Materials and methods. The research included retrospective and prospective stages. At the first stage, the analysis of primary medical records was carried out, and histories of 70 patients over 18 years old, before the onset of autoimmune bullous dermatosis were analyzed. Clinical and epidemiological data were taken into account, the main and concomitant diagnoses were determined in accordance with ICD X. The Charlson index was calculated for all patients, the 10-year viability rate of patients with autoimmune bullous dermatoses was determined.

Results. Polymorbid pathology was recorded in 81.4% of patients, before the onset of autoimmune bullous
dermatosis. 48.6% of patients had two or more concomitant diseases. Among patients with diseases of internal organs, those with cardiovascular pathology (52.8%) occupied the first place, patients with gastroenteric pathology (41.4%) occupied the second place, patients with endocrinopathy held the third place (20.0%). The Charlson index median in patients of this group was 2.5 (1–3), the risk of fatal outcome over a 10-year period was 16.5%. Subsequently, after the onset of autoimmune bullous dermatosis, 65.7% of patients required the prescription of glucocorticosteroid therapy. Decompensation of concomitant pathology was diagnosed in 39.1% of patients, therefore they needed consultation of related specialists. The median polymorbidity index increased to 3.5 (2–5), the risk of a death increased to 34.5% (p < 0.05).

Conclusion. Polymorbid pathology worsens the course of autoimmune bullous dermatoses, increases the risk of disability and mortality, especially in patients receiving systemic glucocorticosteroid therapy, and therefore these patients should be under regular medical check-up not only of a dermatovenereologist, but also of related specialists.

The aim of the study: to reveal the particularities of the concentration of cytokines IL4, IL6, IL10, IL17, IFNγ in blood serum in children with autism spectrum disorder (ASD).

Materials and methods. The blood samples obtained from children of two study groups: children with autism spectrum disorder (n = 93) and clinically healthy children (n = 30), served as the material for the  study. Cytokine concentrations were determined in blood serum using the Bender Medsystems (Austria) kits  for IL17A and Vector-Best (Russia) kits for IL4, IL6, IL10, IFNγ. Serum cytokine concentrations were determined by enzyme immunoassay using kits for IL17A (Bender Medsystems, Austria), IL4, IL6, IL10, IFNγ (Vector-Best, Russia). Assessment of cognitive and psychophysiological indicators in children was performed using the  Autism Treatment Evaluation Checklist (ATEC).

Results. The concentrations of IL17A (U = 54; p = 0,015) and IFNγ (U = 4.64; p = 0,006) were increased and the concentrations of IL6 (U = 327; p = 0.001) and IL4 (U = 177; p = 0.001) were decreased in children with ASD. The concentration of IL6 correlates with the concentration of IL4 (r = 0.68; p < 0.05). The concentration of IL17A correlates with the concentration of IFNγ (r = 0.41; p < 0.05), IL6 (r = 0.87; p < 0.05) and ATEC score (r = 0.24; p < 0.05) in the group of children with ASD.

Conclusion. The cytokine disbalance in children with ADS, which was observed in our study, confirms the  hypothesis of their participation in the development of the disease and clearly shows the Th17  immunoregulation pathway in the pathogenesis of the autism spectrum disorder.

The aim of this study was to identify features of the expression of pro-inflammatory and co-stimulatory molecules on the surface of macrophages in vitro in patients with pulmonary tuberculosis, depending on the clinical form of the disease and sensitivity of the pathogen to anti-TB drugs.

Materials and methods. 40 patients (36 men and 4 women) with pulmonary tuberculosis (TB) were examined: 18 patients (16 men and 2 women, average age (44.56 ± 8.10) years) with disseminated tuberculosis (DTB) and  22 patients (20 men and 2 women, average age (46.54 ± 5.24) years) with infiltrative tuberculosis (ITB). Of those, 30 patients secreted Mycobacterium tuberculosis (MBT) sensitive to the basic anti-TB drugs (ATBD), and 10 patients secreted MBT resistant to first-line anti-TB drugs. Venous blood was the study material. To isolate monocytes from the whole blood in order to transform them into macrophages, ficoll density gradient centrifugation with gradient density of 1.077 g/cm3 was used followed by immunomagnetic separation of CD14+ cells. Monocytes were cultured in a complete culture medium X-VIVO 10 with gentamicin and phenol red with the addition of the macrophage colony-stimulating factor (M-CSF) (5 ng/ml) at a concentration of 1×106 cells/ml with the following stimulators: interleukin (IL) 4 (10 ng/ml) and interferon (IFN) γ (100 ng/ml). Immunophenotyping of macrophages was performed using monoclonal antibodies to CD80, CD86, and HLA-DR on a Beckman Coulter CytoFLEX LX flow cytometer (Beckman Coulter, USA). The analysis of the obtained data was carried out using the CytExpert 2.0 software application. The results were analyzed using statistical methods.

Results. The number of intact and cytokine-stimulated (IL-4 and IFNγ) CD80-positive macrophages in patients with ITB and drug-resistant TB (DR TB) exceeded their number not only in healthy donors, but also in patients with DTB and drug-sensitive TB (DS TB), respectively. In addition, an increase in CD86 expression on the surface of macrophages was registered in patients with ITB and DR TB after adding IFNγ (M1-activation inducer) to the suspension culture. In contrast, in patients with DTB and DS TB, the number of macrophages with expression of B7 family co-stimulating molecules decreased or remained within the normal values in the absence of a reaction to cytokines during cytokine induction. Deficiency of HLA-DR-positive macrophages was found in all TB patients. The minimal number of macrophages expressing HLA-DR was found in patients with DTB and DS TB after cell incubation with IL-4 (M2-activation inducer).

Conclusion. Evaluation of the expression of B7 (CD80/86) and HLA-DR membrane molecules on macrophages in TB patients allows to conclude that anti-TB immune response is impaired at stages of antigen presentation (in all examined patients with TB) and co-stimulation (in DTB and DS TB). An increase in the expression of macrophage surface molecules CD80 (with M1- and M2-stimulation) and CD86 (with M1-stimulation) in patients with ITB and DR TB indicates an increase in cell reactivity in these forms of TB. In addition, deficit of expression of HLA-DR (a key marker of pro-inflammatory cell activation) on the surface of macrophages in TB can be considered as a general (independent of the clinical form of the disease and drug sensitivity of the pathogen) pathogenetic factor of immune imbalance in pulmonary tuberculosis.

The aim of this study was to investigate the prevalence of Internet addiction (IА) and the structure of consumed content among adolescents in Central Siberia.

Materials and methods. From January to May 2019, 3,012 adolescents (45.8% of boys and 54.2% of girls) aged 12–18 years were examined (average age 14.5 ± 1.3 years). Younger adolescents (12–14 years old) accounted for 52.5%, and seniors (15–18 years old) accounted for 47.5%. Peculiarities of online behavior were evaluated according to Chen’s Internet Addiction Scale (CIAS) adapted by V.L. Malygin and K.A. Feklisov; a  total CIAS score of ≥ 65 indicated Internet addiction. Gambling addiction was rated according to the Game Addiction Scale for Adolescents, and addiction to social networks was rated according to the Social Media Disorder Scale. The structure of the consumed content was estimated in the overall sample and in two age groups. The data obtained were processed by non-parametric statistical methods using the Statistica 12.0 software. Quantitative characteristics are presented as the median and the interquartile range Me (Q25 – Q75), binary signs are represented as a share (%) and the confidence interval. The significance of the  differences (p) for quantitative indicators was evaluated by Mann – Whitney U-test and for binary characters by Pearson’s χ2 criterion. The differences between the groups were considered statistically significant at p ≤ 0.05.

Results. The overall prevalence of IА was 6.9%, adaptive use of the Internet was observed in 49.4% of adolescents, non-adaptive use was registered in 43.6% of cases. The frequency of Internet addiction increases with age: from 6.0% in 12–14 year-old adolescents to 8.0% in 15–18 year-old adolescents (p = 0.0324). Content consumed by adolescents included gambling addiction (11%), addiction to social networks (8.0%), mixed IA (2.6%), and undifferentiated Internet addiction (2.8%). Younger adolescents are more often dependent on online games (12.2%), social networks (9.3%), and mixed IА (3.3%), while in older adolescents, undifferentiated IА is more often observed (39.5%).

Conclusion. High level of IA prevalence in adolescents in Central Siberia confirms the relevance of this problem and indicates the need to develop preventive measures aimed at maintaining child and adolescent health.

The presented review highlights the peculiarities of cardiovascular system damages in burn injury. The epidemiological data on the incidence of thermal injuries are reported. The pathogenic mechanisms of heart disorders during various periods of burn injury, as well as pathological changes in the myocardium are examined in detail. The main clinical manifestations of heart damage on the background of burn disease have been identified (heart failure, myocarditis, infectious endocarditis, cardiac arrhythmias and conduction disturbances, myocardial infarction). Special attention is paid to laboratory and instrumental methods for investigation of the heart with a discussion of the benefits and disadvantages of each method. The manuscript discusses the main therapeutic approaches for the management of burn patients with cardiac pathology, as well as the possibilities of using and the effectiveness of modern treatment methods aimed at improving survival, diminishing the severity of cardiovascular disorders and improving the prognosis of such patients.

Implementation of virtual patients allows avoiding risks for patient safety, using the standardized clinical situations repeatedly, and providing remote access to information. In order to create virtual patients, the project team comprised of specialists competent in the diverse subject areas. Every virtual patient is a structural model for a diagnostic and treatment process of a real patient augmented with textual and multimedia information. A sample comprising of 50 archival clinical charts of patients with typical cardiovascular diseases and rare pathology variants was formed. Textual information from medical records is supplemented with the multimedia results of instrumental and laboratory studies. Created data and knowledge base of virtual patients was designated for a demonstration of complete cardiovascular cases to the trainees in linear trajectory with an option of Web-access. The virtual patient repository will become a factual basis for problem-based distance learning of medical students and physicians.

The article discusses modern ideas about the role of extracellular matrix (ECM) and cellular elements of connective tissue (CT) in tissue homeostasis in normal and pathological conditions. The works of recent years reflect a shift of interests concerning the study of many pathological processes, particularly carcinogenesis, to the state of the ECM and CT cells, which are considered as active components of the tissue that determine the processes of cellular proliferation, differentiation, migration, and apoptosis. The most important properties of the ECM attracting the attention of researchers include mechanotransduction, leading to the activation of cytoskeletal mechanisms and various cell signaling pathways; modeling of the effects of various cytokines, growth factors, and hormones; maintenance of the stem cell niches; influence on the emergence and course of the tumor process, in particular, formation of a cancerized field and premetastatic niches; and the epithelial-mesenchymal transition (EMT). Currently, CT cells are also an important object of study, in particular, fibroblasts, which are the main producers of ECM components. The attention of researchers is directed primarily to cancer-associated fibroblasts, the phenotype of which forms in the tissue long before the tumor appears. New knowledge about the role of ECM and CT cells in tissue homeostasis determines new approaches to treatment of many diseases, such as systemic sclerosis, tumors, etc.

Aim: analysis of all known markers of proliferation, apoptosis, autophagy and angiogenesis in the pathogenesis of Barrett’s esophagus and esophageal adenocarcinoma with the purpose of improvement of diagnostics and  treatment quality.

Materials and methods. Analysis of the available scientific sources by Russian and foreign authors.

Results. Data on all the known markers has been structured and is supposed to be integrated into clinical practice in the diagnosis and treatment of Barrett’s esophagus and esophageal adenocarcinoma at various stages  of disease development. 

Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disease. Its molecular cause is a cytosine-adenine-guanine (CAG) trinucleotide repeat dynamic expansion in the huntingtin (HTT) gene. Alleles with 36–39 CAG-repeats are incompletely penetrant, as individuals might develop symptoms but typically with a later age of onset. When repeats are equal or greater than 40, the symptoms of the disease occur. It is considered that CAG-repeats in the “intermediate” alleles (27–35 repeats) also cause the symptoms of the HD.
We present here the case of a patient who has clinical phenotype and family history of Parkinson’s disease (PD), but 27 CAG-repeats. The feature of this patient is early development of non-motor manifestations such as cognitive impairment, psychotic disorders, early dystonia in a hand, camptocormia and poor response to levodopa. It is believed that the intermediate allele of HTT gene might modify the clinical phenotype of PD in this patient.

The case of metastatic heart damage manifesting by a clinical picture of acute myocardial infarction in a patient with urothelial carcinoma of the urinary bladder is described. A 69-year old patient was admitted with the symptoms of acute myocardial infarction from the neurological department, where he was hospitalized due to a space-occupying lesion of the right hemisphere of the brain, which manifested in a convulsive episode with the development of leftsided spastic hemiparesis. After coronary angiography, percutaneous coronary intervention was performed for the lesions of the anterior interventricular branch of the left coronary artery. Despite the complex of the therapeutic  measures, the patient died. A pathological study revealed urothelial carcinoma of the bladder with distant metastases to the brain and myocardium. This clinical case demonstrates the situation of intravital diagnosis of metastatic myocardial lesions, which requires a determination of the treatment approach in the described category of patients.