Aim. To study the characteristics of the course of arterial hypertension (AH) and subclinical cardiac damage during breast cancer chemotherapy with doxorubicin.

Materials and methods. The study included a total of 27 women with breast cancer (BC) and a history of controlled hypertension who were to receive chemotherapy with anthracyclines. Twelve women had stage 1 hypertension; 15 women had stage 2 hypertension. The patients received dual antihypertensive therapy according to clinical guidelines. All patients underwent echocardiography and 24-hour blood pressure monitoring at baseline, after the last course of chemotherapy, and 12 months after the end of chemotherapy. The control group included 35 women with BC without a history of AH, who also were to receive anthracycline chemotherapy.

Results. A significant relationship between pre-existing AH and the development of left ventricular systolic dysfunction 12 months after the completion of chemotherapy (p = 0.01) was found. According to 24-hour blood pressure monitoring, 15 women (55.6%) showed deterioration of blood pressure control after the completion of chemotherapy, which required modification of antihypertensive therapy by adding one more drug to the treatment regimen. At 12 months after the end of chemotherapy, in 13 women, hypertension control was reached with triple antihypertensive therapy. In two women, hypertension became resistant, which required prescription of a fourcomponent antihypertensive regimen.

Conclusion. Pre-existing AH plays an essential role in the development of anthracycline-induced cardiotoxicity, despite the quality of blood pressure control. Polychemotherapy with anthracyclines may deteriorate blood pressure control in patients with AH, which requires addition of antihypertensive drugs to the treatment regimen.

Aim. To study in vitro and in vivo the functional suitability of ^99mTc-labeled lyophilized formulation containing designed ankyrin repeat protein (DARPin) G3-(GGGS)₃Cys for radionuclide imaging of HER2/neu overexpression in malignant tumors.
Materials and methods. To create a targeted protein, a modified genetic construct with the sequence encoding DARPin G3-(GGGS)₃Cys was used. To generate the experimental probe, we used a lyophilized formulation containing DARPin G3-(GGGS)₃Cys with auxiliary substances and ^99mTc sodium pertechnetate (500 MBq) incubated at 60 °C for 30 min. Radiochemical purity of ^99mTc-G3-(GGGS)₃Cys was analyzed by thin-layer radiochromatography. SKOV-3, BT-474, and DU-145 cell lines were used to test binding specificity in vitro. The dissociation constant was determined via a saturation binding assay on SKOV-3 cells with a range of protein concentrations from 0.2 to 40 nM. Nu/j mice bearing HER2-positive SKOV-3 xenografts and HER2-negative Ramos xenografts were used to evaluate the targeting properties and biodistribution.
Results. A radiocomplex based on ^99mTc and a lyophilized formulation with DARPin G3-(GGGS)₃Cys was obtained with the radiochemical purity of more than 96%. Binding of ^99mTc-G3-(GGGS)₃Cys to the cells was specific (K_D 3.9 ± 0.5 nM) and proportional to the level of HER2/neu expression in the cells. The uptake of ^99mTc-G3-(GGGS)₃Cys in SKOV-3 xenografts was significantly higher than in Ramos xenografts. ^99mTc-G3-(GGGS)₃Cys demonstrated rapid blood and renal clearance and had low activity in the salivary glands and stomach. Liver uptake was about 5–7%ID/g. In addition, ^99mTc-G3-(GGGS)₃Cys exhibited very low uptakes in the lungs, muscles, small intestine, and bones.
Conclusion. The ^99mTc-labeled lyophilized formulation with DARPin G3-(GGGS)₃Cys is functionally suitable for imaging HER2/neu overexpression in tumors, as it binds specifically to the receptor, is stable in vivo, and has favorable biodistribution in organs and tissues. The radiocomplex based on ^99mTc-G3-(GGGS)₃Cys was obtained by a simple method with high radiochemical purity.

Aim. To perform a comparative assessment of subset composition and functional activity of peripheral blood lymphocytes in patients with tick-borne encephalitis (TBE) and ixodid tick-borne borreliosis (ITBB) in the acute phase of the disease.

Materials and methods. The study involved 22 patients with febrile and meningeal TBE, 15 patients with ITBB with and without erythema, and 11 healthy controls. Subset composition of blood lymphocytes was determined by flow cytometry. The blast transformation assay was applied to assess lymphocyte proliferation. Cytokine-producing activity of cells was studied in 24-hour incubated mononuclear cell cultures. Cytokine concentrations (interleukin (IL)-2, IL-4, IL-10, interferon (IFN)γ) were determined in the supernatants by the enzyme-linked immunosorbent assay (ELISA).

Results. Patients with TBE demonstrated an increase in the proportion of helper – inducer T-cells, a pronounced decrease in the proportion and absolute count of cytotoxic T cells, and low T lymphocyte count compared to the control values. The study in ITBB patients revealed an increase in the helper – inducer T-cell count and the proportion of NK-cells, a decrease in the cytotoxic T cell count, and the T lymphocyte count comparable to normal values. The most significant decrease in the levels of phytohemagglutinin-induced lymphocyte proliferation was found in patients with TBE. Patients of both groups showed a decrease in IL-2 secretion in the mononuclear cell culture, a rise in IL-4 and IL-10 production, and IFNγ production levels comparable to control values.

Conclusion. The study of TBE patients revealed relative lymphocytopenia with changes in the subset composition of lymphocytes characterized by an increase in the proportion of helper – inducer T-cells and a decrease in the absolute cytotoxic T lymphocyte count. Patients with ITBB demonstrated an increase in the proportion of NK-cells and a more pronounced imbalance in the T-helper / cytotoxic T lymphocyte ratio. Changes in the functional phenotype of lymphocytes, regardless of the etiology of tick-borne infection, were characterized by reduced proliferative reserve, low IL-2 secretion, increased IL-4 and IL-10 production, and depressed reactivity of lymphocytes with respect to IFNγ secretion.

Aim. To study the levels of adipocytokines and their associations with stable and unstable atherosclerotic plaques in patients with a high triglyceride – glucose (TyG) index.

Materials and methods. The study included 109 men aged 38–79 years (mean age 62.28 ± 8.19 years) with atherosclerosis hospitalized for coronary artery bypass grafting (CABG). After microscopy of the intima – media layer, the type of atherosclerotic plaque was determined: stable / unstable. The TyG index ≥ 4.49 was considered as high. Fifty-eight (60%) men had stable plaques in the CA (28 (56%) of them had TyG ≥ 4.49); 39 (40%) men had unstable plaques in the CA (15 (39%) had TyG ≥ 4.49). Blood adipocytokine level was studied using the multiplex assay and the Human Metabolic Hormone Panel V3.

Results. The final analysis included 97 patients. The level of glucose-dependent insulinotropic polypeptide (GIP) was 1.53 times greater in patients with TyG ≥ 4.49 (34.16 [18.71; 54.98] vs. 22.34 [15.02; 34.77], p = 0.004). In patients with TyG < 4.49, the adipsin level was 1.2 times higher in patients with unstable plaques than in patients with stable ones. In patients with stable plaques and TyG ≥ 4.49, the GIP level was 1.88 times higher than in patients with TyG < 4.49 (42.13 [25.34; 68.95] vs. 22.39 [17.00; 28.60], p = 0.003). In patients with unstable plaques and TyG ≥ 4.49, the level of peptide tyrosine – tyrosine (PYY) was 1.46 times greater than in patients with TyG < 4.49 (46.14 [30.49; 70.66] vs. 31.53 [24.71; 43.01], p = 0.048).

Conclusion. Men with atherosclerosis and TyG ≥ 4.49 had higher blood levels of GIP and PYY. Blood adipsin levels were higher in patients with unstable plaques without insulin resistance.

Aim. To study the analgesic activity, the effect on motor functions, and the potential ulcerogenic effect of a new 2H-chromene derivative, a cannabinoid CB₁ receptor modulator (code name – CHR).

Materials and methods. The analgesic activity of the CHR compound was studied when injected intragastrically at an effective dose of 5 mg / kg in mouse models of acute chemogenic pain (formalin test), acute visceral pain (the acetic acid-induced writhing test), and thermal nociception (hot plate test and tail-flick test). It was compared to the effect of tramadol and morphine or diclofenac sodium at doses of 20, 4 or 10 mg / kg, respectively. The effect of a single intragastric injection of the CHR compound at a dose of 5 mg / kg on motor activity was evaluated in the open field test. The potential ulcerogenic effect of the CHR compound at a dose of 5 mg / kg with repeated intragastric administration was compared with the effect of diclofenac sodium at a dose of 10 mg / kg.

Results. With subplantar administration of formalin to mice, the 2H-chromene derivative reduced the number of pain reactions by 43–63% (p < 0.05). With intraperitoneal administration of acetic acid to mice, it reduced the number of writhing responses by 50% and had the same analgesic effect as diclofenac sodium and tramadol. In the hot plate test, the CHR compound increased the latency time to painful stimuli by 34% (p < 0.05). In the tailflick test, it increased the latency time to painful thermal sensations by 32% (p < 0.05). The CHR compound at an effective dose of 5 mg / kg did not change the motor activity of mice in the open field test and did not cause the formation of erosions and ulcers in the gastric mucosa when administered repeatedly to rats.

Conclusion. The 2H-chromene derivative CHR at an effective dose of 5 mg / kg has a pronounced analgesic effect in mouse models of chemogenic, visceral, and thermal pain, which is as strong as that of tramadol, morphine, and diclofenac sodium used at effective doses. The CHR compound at an effective dose does not inhibit motor functions and does not have an ulcerogenic effect.

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.

Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.

Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p < 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p < 0.001), whereas markers of endothelial dysfunction were not independent predictors.

Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

Aim. To investigate the protective effect of dalargin on the content of goblet cells and mucins in the colonic mucosa in a mouse model of ulcerative colitis.

Materials and methods. Ulcerative colitis was simulated in Balb/C mice by replacing drinking water with 5% sodium dextran sulfate in boiled water for 5 days. Dalargin was administered subcutaneously in a volume of 0.1 ml at a dose of 100 μg / kg of body weight once a day for 7 days from the beginning of ulcerative colitis simulation. Sulfasalazine as a reference-listed drug was administered intragastrically at a dose of 200 mg / kg once a day for 7 days. The mice were sacrificed on day 5, 7, and 28. The sections of the distal colon were prepared and stained with hematoxylin and eosin, alcian blue (pH = 1.0) according to Mowry or by PAS reaction. In the sections, the number of goblet cells and acid and neutral mucins was determined.

Results. In the mouse model of ulcerative colitis, the number of goblet cells (mainly at the bottom of the crypts), acid and neutral mucins decreased. Dalargin administration increased the number of goblet cells and the content of acid and neutral mucins in the colonic mucosa more effectively than sulfasalazine.

Conclusion. Dalargin has a protective effect in ulcerative colitis.

The aim of the work was to study the cardioprotective effect of lithium ascorbate in an in vivo model of myocardial infarction. In the course of the study, we searched for compounds promising for therapy of acute myocardial infarction.

Materials and methods. Myocardial infarction was modeled in Wistar rats by ligating the left coronary artery (the duration of ischemia was 45 minutes) followed by ligature loosening and 120-minute reperfusion. All manipulations were performed under alpha-chloralose anesthesia with mechanical lung ventilation and recording heart rate, blood pressure, and ECG. Lithium ascorbate was administered intravenously at a dose of 100 mg / ml before ischemia. The area at risk (the ischemia / reperfusion zone) was detected by staining the myocardium with tightened ligature with 5% potassium permanganate. After that consecutive myocardial slices were prepared, and infarct size was determined. Differentiation of the infarct size from the area at risk was performed by staining with 1% 2,3,5-triphenyl tetrazolium chloride solution for 30 minutes at 37 ºC. The infarct size and the area at risk were determined by the planimetric method. The serum concentration of myocardial damage marker creatine kinase-MB (CK-MB) was measured using ELISA kits.

Results. Lithium ascorbate reduced the infarct size / area at risk ratio by 38% and decreased the serum CPKMB level in the experimental animals by 42% compared to the control group. Lithium ascorbate did not affect hemodynamics parameters during coronary artery occlusion and reperfusion.

Conclusion. The cardioprotective effect of lithium ascorbate in cardiac ischemia / reperfusion in vivo was found.

Aim. To study the effect of a new complex compound LHT-2-20 (2-ethyl-6-methyl-3-hydroxypyridine-2-(3benzoyl phenyl)-propanoate) on free radical oxidation in experimental periodontitis.

Materials and methods. The experimental study was performed on 195 white mongrel mice weighing 19–23 g and 137 white mongrel rats weighing 180–220 g. The effect of a new complex compound LHT-2-20 (2-ethyl-6methyl-3-hydroxypyridine-2-(3-benzoyl phenyl)-propanoate) on the intensity of free radical oxidation and the local state of periodontal tissues during a course of intragastric administration was studied on the experimental model of periodontitis. Statistical processing of the results was carried out using the SPSS Statistics 20.0 software package with the analysis of variance (ANOVA) and the parametric Tukey’s test.

Results. The LHT-2-20 compound reduced elevated levels of primary and secondary lipoperoxidation products (conjugated dienes, malondialdehyde in plasma and in erythrocytes during spontaneous and iron-induced oxidation) already at the early stages of the experiment, bringing the studied parameters closer to the reference values by the end of the course of treatment. The use of the compound LHT-2-20 contributed to an increase in the activity of the main antioxidant enzymes (catalase and superoxide dismutase), normalizing them to baseline values by the end of the experiment. With the correction of free radical processes, the use of LHT-2-20 limited the local inflammatory response in periodontal tissues, which was confirmed by a decrease in gingival edema and hyperemia, bleeding, depth of periodontal pockets, and tooth mobility.

Conclusion. The results of this study confirm the anti-inflammatory potential of the compound and the multiplicity of its effects due to the impact on the mechanisms of oxidative stress. The expediency of further study of the drug is justified by the prospect of creating a new drug and its subsequent wide clinical application as part of the complex therapy of periodontal inflammation.

Aim. To evaluate β-adrenergic reactivity of erythrocyte membranes (β-ARM) in adolescents with ventricular and supraventricular arrhythmias before and after radiofrequency ablation (RFA) of heart rhythm disturbances.

Materials and methods. The study included 49 adolescents aged 11–17 years, of which 15 had Wolff – Parkinson – White pattern (WPW), 13 – WPW syndrome, 10 – atrioventricular nodal reentry tachycardia (AVNRT), and 11 – ventricular arrhythmia (VA). The control group consisted of 11 adolescents without cardiovascular pathology. All patients received surgical treatment for heart rhythm disturbances (HRD) using RFA. In patients with HRD, β-ARM was determined by a set of reagents BETA-ARM AGAT (AGAT LLC, Russia) before RFA and 3 days after it. In the control group, the parameter was determined at the stage of inclusion in the study.

Results. In adolescents with supraventricular arrhythmias, median values of β-ARM did not differ significantly from the control group. RFA in adolescents in these groups did not affect the value of β-ARM on day 3 after the surgery. In adolescents with VA, the median value of β-ARM was initially higher than in the control group (p = 0.026). On day 3 after RFA, an increase in β-ARM was noted in this group (p = 0.028) compared to baseline values.

Conclusion. Activation of the sympathetic nervous system plays a significant role in the pathogenesis of VA in adolescence. The study showed the possibility of using β-ARM to assess the state of the sympathetic nervous system in patients with methodological limitations in analyzing heart rate variability.

Aim. To elaborate a decision rule for identifying the main predictors of impaired lung diffusion capacity after COVID-19.

 Materials and methods. The retrospective study included 341 patients without underlying lung diseases (median age 48 years) who experienced COVID-19 with bilateral pneumonia. The median extent of parenchymal lesion in the acute phase of COVID-19 (CT_max) was 50%. Spirometry, body plethysmography, and lung diffusion capacity for carbon monoxide (DLCO) test were performed. The data were analyzed by descriptive statistics, correlation analysis, one-dimensional logistic regression analysis with an assessment of odds ratios (OR), and multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess the quality of the binary classifier model.

Results. The initial model for predicting reduced DLCO (< 80% of predicted) included the following predictors: CT_max, time interval from the COVID-19 onset, gender, age, body mass index. Backward stepwise regression was applied, and a binary classifier model that includes CT_max was obtained. The sensitivity and specificity of the model for the training sample were 80 and 67%, respectively, for the test sample – 79 and 70%, respectively. The analysis of OR showed that OR > 1 was observed at СT_max > 40%.

Conclusion. The decision rule was obtained for predicting impaired lung diffusion capacity after COVID-19 with virus-associated lung damage in patients without underlying bronchopulmonary diseases. Patients with CT_max > 40% require more thorough clinical follow-up with DLCO monitoring after the acute phase of COVID-19

Background. Intestinal microbiota is one of the most important factors determining the state of human health, including its influence on the immunological mechanisms regulating the development of allergic diseases in childhood. The role of intestinal microbiota and the gut – lung axis in the development of bronchial asthma (BA) is an important area of research.

Aim. To analyze the taxonomic composition of intestinal microbiota in children with BA using 16S rRNA gene sequencing.

Materials and methods. The study included patients with BA (n = 50, mean age 10.34 ± 2.99 years) and a group of apparently healthy individuals (n = 49, mean age 10.3 ± 2.8 years). For all patients, medical history was taken, and physical examination and stool test were performed. Patients with BA were assessed for the level of total and specific immunoglobulin (Ig) E and underwent spirometry. The microbiota composition was analyzed by 16S rRNA gene sequencing with subsequent bioinformatic and statistical analysis.

Results. Significant differences in the composition of the intestinal microbiota (beta diversity) and a decrease in taxonomic diversity (alpha diversity) were found in patients with BA compared to healthy controls. The intestinal microbiota of patients with BA was characterized by an increase in the abundance of Bacteroides, Parabacteroides, Lachnospira, Roseburia, Akkermansia, Anaerostipes, Sutterella, Odoribacter, Phascolarctobacterium, Butyricimonas, as well as unclassified bacteria from the Rikenellaceae families. The intestinal microbiota of children without BA was characterized by greater abundance of bacteria from Blautia, Bifidobacterium, Dorea, Ruminococcus, Streptococcus, Eubacterium, Acinetobacter, Collinsella, Lactococcus, Catenibacterium genera and unclassified bacteria from the Clostridiaceae and Coriobacteriaceae families. Significant differences in the quantitative abundance of bacteria were revealed depending on the type of sensitization, the level of total IgE, and the value of FEV1.

Conclusion. The results obtained indicate the differences in the intestinal microbiota composition in children with BA and healthy children.

Aim. To study the frequency of cardiohepatic syndrome and steatosis by the value of controlled attenuation parameter (CAP), fibrosis, and their combination, depending on the degree of glucose metabolism disorder in patients with acute decompensated heart failure (ADHF).

Materials and methods. The study included 280 patients (53% men, average age 70.1 ± 10.8 years) with ADHF: 72.5% of patients had a history of arterial hypertension, 60% of patients had coronary heart disease. The HbA1c test was performed in all patients to assess the status of glucose metabolism. The patients were divided into groups depending on the results obtained: at HbA1c values < 5.7%, patients were included in the group without glucose metabolism disorders, at HbA1c 5.7–6.4% – in the prediabetes group, at HbA1c ≥ 6.5% – in the type 2 diabetes group. All patients underwent a standard physical examination at admission and at discharge. Clinical and comprehensive assessments of congestion were performed – NT-proBNP, lung ultrasound, liver fibroscan with CAP, and bioelectrical impedance analysis of body composition.

Results. The frequency of glucose metabolism disorders in patients hospitalized with ADHF was 57.5% (n = 161), while prediabetes was detected in 17.1% (n = 48) and type 2 diabetes – in 40.4% (n = 113) of patients. We revealed significantly higher incidence of steatosis by CAP value (69 vs. 42%, p < 0.001), fibrosis (80 vs. 64%, p < 0.001), and their combination (59 vs. 30%, p < 0.001), as well as cardiohepatic syndrome (87 vs. 61%, p < 0.001) in patients with ADHF and glucose metabolism disorders compared to individuals with ADHF without glucose metabolism disorders, respectively. The group of ADHF patients with glucose metabolism disorders and a combination of steatosis / fibrosis was characterized by more pronounced manifestations of metabolic syndrome, impaired kidney and liver function, and more pronounced manifestations (both clinical and laboratory) of congestion.

Conclusion. In patients with ADHF with glucose metabolism disorders, liver function test and liver fibroscan with CAP allow for identifying the most severe group of patients with a combination of steatosis/fibrosis and pronounced congestion.

Aim. To perform a comparative analysis of leukopoiesis parameters and platelet count in peripheral blood with evaluation of their changes in the first 48 hours from urosepsis (US) verification in hospitalized patients depending on the outcome of the disease.

Materials and methods. A retrospective comparative study included 40 patients with US divided into a group of deceased (n = 10) and a group of recovered (n = 30) individuals. Along with a full clinical and paraclinical examination, which is a routine practice in the urology clinic in case of suspected (confirmed) sepsis, we performed a differentiated assessment of leukopoiesis and platelet count in peripheral blood at baseline (at the moment of US verification) and 48 hours after US verification. The assessment included determination of the immature granulocyte count, investigation of neutrophil granularity intensity (NEUT-GI) and neutrophil reactivity intensity (NEUT-RI), and measurement of the mean platelet volume (MPV).

Results. The baseline level of organ dysfunction graded by the SOFA (Sequential Organ Failure Assessment) score was significantly higher in deceased patients than in survivors (6 points vs. 3 points, respectively; p = 0.001). The group of the deceased was characterized by lower platelet and monocyte levels. The ROC analysis with the calculation of area under the curve (AUC) identified the following potential predictors of a lethal outcome in US: proportion of monocytes from the total leukocyte count at baseline ≤ 5.5% (AUC 0.732, p = 0.032), proportion of eosinophils from the total leukocyte count at baseline ≤ 0% (AUC 0.756, p = 0.011), absolute eosinophil count at baseline ≤ 0.01 × 10⁹ / l (AUC 0.802, p = 0.009), absolute basophil count at baseline ≤ 0.03 × 10⁹ / l (AUC 0.718, p = 0.028), NEUT-GI at baseline ≤ 153.2 scatter intensity (SI) units (AUC 0.754, p = 0.021), NEUT-RI at baseline ≤ 59.3 SI units (AUC 0.737, p = 0.024) and their increase after 48 hours by > 0.9 SI units (AUC 0.852, p = 0.001) or by > 1.34% (AUC 0.844, p = 0.003), platelet count at baseline ≤ 144 × 10⁹ / l (AUC 0.762, p = 0.007) and after 48 hours ≤ 174 × 10⁹ / l (AUC 0.769, p < 0.007).

Conclusion. The assessment of the platelet count and leukopoiesis parameters, including the ones characterizing neutrophil maturation (NEUT-RI, NEUT-GI), in the first 48 hours from US verification, can be effective predictors of a lethal outcome in patients with US.

Aim. To assess the prevalence of elevated serum liver transaminases (LTs), including alanine aminotransferase (ALT) and aspartate aminotransferase (ALT), and their impact on in-hospital and long-term mortality in patients with acute myocardial infarction (AMI).

Materials and methods. The prospective observational study included 416 consecutive AMI patients (median age 65 years, 40.9% female, 46.9% with ST elevation) without prior liver diseases, who underwent coronary angiography within 24 hours after hospitalization. AST and ALT levels were measured upon admission. LTs were considered as abnormal when their levels exceeded the local upper limit of normal. Clinical endpoints were all-cause in-hospital and 18-month mortality. Associations between clinical endpoints and various risk factors, including LT levels, were assessed by the multivariate logistic regression analysis.

Results. Elevated LT levels were seen in 28.6% of AMI patients: an isolated increase in ALT was noted in 17.8% of patients, while an isolated increase in AST was registered in 25% of cases. In-hospital and 18-month mortality was 5.8 and 11.3%, respectively. Abnormal LT levels were associated with the presence of ST elevation (odds ratio (OR) 1.873, 95% confidence interval (CI) 1.218–2.881, p = 0.004), lower systolic and diastolic blood pressure (OR 0.993, 95% CI 0.986–1.0, p = 0.04 and 0.979, 95% CI 0.964–0.994, p = 0.007, respectively), higher Killip class (OR 1.510, 95% CI 1.142–1.999, p = 0.004), and higher creatinine level (OR 1.010, 95% CI 1.003–1.016, p = 0.004). In the multivariate analysis, elevated LT levels were independently associated with in-hospital and 18-month mortality (OR 3.607, 95% CI 1.199–10.848, p = 0.022 and 2.182, 95% CI 1.011–4.708, p = 0.047, respectively).

Conclusion. Elevated LT levels were present in about a third of patients with AMI. They were associated with specific clinical, biological, and prognostic features, including in-hospital and long-term mortality in AMI patients.

The lecture considers the results of research conducted by Russian and foreign scientists concerning the characteristics of all types of metabolic disorders and hormonal imbalance in undifferentiated connective tissue dysplasia (CTD). Understanding the role of hormonal and metabolic disorders in the development and course of diseases associated with CTD is of great importance for the development of pathogenetically grounded algorithms for the diagnosis, treatment, and prevention of emergency conditions.

Proteins of the transforming growth factor beta (TGF-β) family regulate numerous cellular processes that are essential in the pathogenesis of acute respiratory distress syndrome (ARDS), contributing to increased alveolar epithelial permeability, activation of fibroblasts, and extracellular matrix remodeling. TGF-β is involved in the pathogenesis of inflammatory respiratory diseases during the development of COVID-19. SARS-CoV-2 leads to complex immune responses that include the release of inflammatory cytokines, increased activity of mast cells, and the release of mast cell secretome, in particular profibrotic enzymes and cytokines, including TGF-β.

Tryptaseand chymase-positive mast cells play a major role in pulmonary fibrosis and embolism in COVID-19. Mast cell chymase is angiotensin-converting enzyme 2-independent due to extracellular formation of angiotensin II in the interstitium; it also activates TGF-β and other molecules, thereby playing a role in tissue remodeling. Mast cell β-tryptase increases the secretion of TGF-β1 by airway smooth muscle tissue and the expression of α-smooth muscle actin (α-SMA). TGF-β also induces the generation of mitochondrial reactive oxygen species (ROS), which enhances the production of ROS in lung fibroblasts. TGF-β is crucial for induing the synthesis of extracellular matrix components by fibroblasts.

The review is devoted to the structure of TGF-β, the sources of its secretion and functions, the mechanism of its involvement in the pathogenesis of COVID-19, and the possibility of its use as a prognostic marker of COVID-19 severity.

Aim. To consider the use of galectin-1 and galectin-3 inhibitors as potential pharmacological targets in antitumor and antifibrotic therapy.

The lecture includes the analysis of experimental research and review articles presented in the PubMed database. A brief description of the structure of galectins is given. Their generally accepted classification and features of the structure of the carbohydrate recognition domain in galectin-1 and galectin-3 are presented. The main part of the lecture describes the results of research on the development of carbohydrate-based (β-galactoside derivatives or analogues) and non-carbohydrate-based (peptide-based, carboxamide derivatives) inhibitors capable of interacting with galectin-1 and galectin-3.

The results of experiments performed on animal models and tumor cell cultures demonstrate that the antitumor effect of galectin antagonists is realized through the suppression of proliferation and metastasis, activation of tumor cell apoptosis, and modulation of the antitumor immune response. Antagonists of galectin-1 and galectin-3 potentiate the effect of antitumor drugs and have an antifibrotic effect. Some of the compounds discussed in the lecture are undergoing clinical trials. The data presented in the lecture open up opportunities for the development and synthesis of new molecules of potential galectin-1 and 3 inhibitors.

Most intracranial arachnoid cysts are thought to be non-tumorous, congenital, intra-arachnoid cerebrospinal fluid collections that account for about 1% of all intracranial space-occupying lesions. In children, the prevalence of this pathology is 2.6%; in adults, it reaches 1.4%. The disease is more often registered in men. Most often arachnoid cysts are supratentorial. Their most common locations are in the middle cranial fossa and the retrocerebellar cistern. Less often they can be detected on the convexity of the brain hemispheres; however, cases of arachnoid cysts at more unusual sites have also been described, including in newborns. The pathology is often characterized by an asymptomatic course, while certain symptoms may have an acute onset, which is due to compression of brain structures caused by the large cyst size.

This article describes a clinical case of a large intracranial arachnoid cyst in a 28-year-old man. It was not verified in the antemortem diagnosis, but was revealed according to the autopsy findings (macroscopic features of the cyst, histologic presentation with specific morphological changes, and findings of computed tomography of the cerebral hemispheres).

Aim. To study the clinical presentation and differential diagnosis of a rare hereditary disease glycogen storage disease type IV with progressive skeletal myopathy in a case report of a family.

Materials and methods. Two patients were followed up in the specialized neurology unit of the regional clinical hospital and in the outpatient setting.

Results. Long-term follow-up and examination in two clinically similar cases of myopathy in siblings allowed us to diagnose a hereditary metabolic disease. The congenital muscular form of glycogen storage disease type IV was manifested by myopathy and peripheral tetraparesis with the development of bone deformities. Difficulty in the diagnosis was due to isolated myopathy progression with no signs of liver involvement. The diagnosis was established with account of clinical manifestations, the progressive course of the disease, electromyography findings, and the results of molecular genetic testing for pathogenic mutations associated with hereditary neuromuscular diseases.

Conclusion. Glycogen storage disease type IV can clinically manifest itself by progressive myopathy without liver involvement and changes in blood biochemistry. The presented clinical cases in siblings are identical. Myopathy does not have clinical features that are significant for the differential diagnosis with other hereditary neuromuscular diseases. Genetic testing identified a mutation in the GBE1 gene and is considered as the main diagnostic criterion of the disease.