The aim of the study was to assess the levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), and vascular endothelial growth factor A (VEGF-A) in tissue extracts in comparison with the histologic examination of the endometrium and chorionic villi in women with spontaneous abortion and active cytomegalovirus (CMV) infection.

Materials and methods. 81 women at 7–9 weeks of pregnancy were examined: of them, 51 women were CMVseropositive with active infection and after spontaneous abortion, and 30 patients were CMV-seronegative, healthy women after therapeutic abortion. Immunoglobulins (Ig) M and G to CMV and CMV IgG avidity were measured in the blood plasma; sFlt1, PlGF, and VEGF-A were determined in extracts of chorionic villi by enzyme immunoassay. CMV DNA was detected in mononuclear cells of peripheral blood, urine, and chorionic villi by real-time polymerase chain reaction (PCR). A histologic examination of the endometrium and chorionic villi was carried out.

Results. In chorionic villus extracts of women with spontaneous abortion and active CMV infection, the concentration of sFlt1 was 3.25 times higher (p < 0.001), and the levels of PlGF and VEGF-A were 1.31 (p < 0.001) and 2.16 times lower (p < 0.001) than in healthy women. A strong negative correlation was established between the levels of sFlt1 and PlGF (r = –0.702; p < 0.001) and VEGF-A (r = –0.858; p < 0.0005), and a positive correlation was revealed between PlGF and VEGF-A levels (r = 0.860; p < 0.001). According to the data of the histologic examination, a lag in decidual transformation of uterine vessels, trophoblast invasion, growth and differentiation of villi, and formation of fetal circulation was detected.

Conclusion. The mechanisms of spontaneous abortion in women with active CMV infection include an imbalance of pro- and anti-angiogenic factors, which causes impaired placental development and uteroplacental circulation.

Seborrheic dermatitis is a chronic relapsing inflammatory skin disease associated with overproduction of sebum and activation of the fungal skin microbiota characterized by the presence of erythematous pruritic patches and plaques with greasy scales in areas rich in sebaceous glands.

Aim. To study the spectrum of sensitization to food, pollen, and indoor and fungal allergens in patients with seborrheic dermatitis.

Materials and methods. The study researched features of the spectrum of sensitization to food, pollen, and fungal and indoor allergens in patients with seborrheic dermatitis (n = 40, aged 15–59 years) based on the data of an objective examination and the results of an allergen-specific test, including skin prick testing.

Results. It was determined that the most significant food allergens in seborrheic dermatitis are chicken eggs and grains. The incidence of polyvalent sensitization to food allergens was 40.0%. Additionally, high incidence of sensitization to pollen allergens, most often to weed and poaceae pollen, was revealed in patients with seborrheic dermatitis. Among indoor allergens, the highest incidence of sensitization was determined to house dust and Dermatophagoides pteronyssinus. Among fungal allergens, the highest incidence of sensitization was detected to Candida albicans. Conclusion. It was found that patients with seborrheic dermatitis are often sensitized to food, pollen, and indoor and fungal allergens. Therefore, allergy can be considered a risk factor for the development of pathology.

The aim of the study was to investigate the pathogenesis of experimental osteoarthrosis induced by dexamethasone and talc by examining the structure and defining the morphometric and metabolic features of knee joint skeletal connective tissues in rats.

Materials and methods. We performed a morphometric evaluation of articular cartilages (their thickness, extracellular matrix arrangement, spatial arrangement of the main components, distribution density, and main cellular indices of chondrocytes), as well as changes in subchondral bones (the presence of trabeculae in the basal layer of the articular cartilage and individual osteophytes) in 30 rats with a model of primary osteoarthrosis induced by sequential administration of 0.5 ml dexamethasone (2 mg) and 1 ml 10% sterile talc suspension mixed with normal saline into the joint cavity. We studied the histologic specimens of the knee joints stained with hematoxylin – eosin, Alcian blue (рН 1.0 and 2.5), as well as with Van Gieson’s, Masson’s, and Mallory’s trichome stains. The metabolic features of the articular cartilage and bone tissues were investigated by determining the hyaluronan, osteocalcin, and type I collagen levels in the serum of the rats.

Results. In the rats with dexamethasone- and talc-induced osteoarthrosis, the thickness of cartilages in their weight-bearing areas decreased by 50%, the spatial arrangement of chondrocytes was impaired, and the nuclear – cytoplasmatic ratio (р < 0.01) decreased to 0.3. Besides, a rise in the serum levels of hyaluronan (p < 0.001) to 110.2 ng / ml, type I collagen fragments (p < 0.001) to 217.9 ng / ml, and osteocalcin (p < 0.001) to 231.1 ng / ml was detected.

Conclusion. The main pathogenetic features of experimental osteoarthrosis induced by dexamethasone and talc include impaired distribution density, morphological characteristics, and functional activity of chondrocytes, which results in inhibited synthesis of extracellular matrix components in the articular cartilage and activated destruction of proteoglycans containing unsulphated glycosaminoglycans. The subchondral bone remodeling in experimental osteoarthrosis induced by dexamethasone and talc is characterized by intensification of synthetic activity of osteoblasts.

Aim. To study the relationship between parameters of the impulsivity – reflexivity cognitive style and the level of Internet addiction among high school students.

Materials and methods. 154 students from general education institutions aged 16–17 years were diagnosed using the J. Kagan’s reflection – impulsivity test and the Chen Internet Addiction Scale. The one-way analysis of variance was used, followed by post-hoc pairwise comparisons using the Tukey’s test.

Results. An inverse relationship between the level of Internet addiction and decision latency in a multiple-choice situation and a direct relationship between the level of Internet addiction and the number of errors in the J. Kagan’s reflection – impulsivity test were revealed.

Conclusion. High school students with propensity to Internet addiction tend to have the impulsive cognitive style, while students without such a tendency – the reflective style. In cognitive activity, the impulsive cognitive style is generally less productive than the reflexive one. The impulsive cognitive style is similar to the so-called clip thinking, which allows to consider the relationship between Internet addiction and this phenomenon through the prism of cognitive and style features.

The aim of this work was to study the levels of podocalyxin and β-2-microglobulin and parameters of lipid metabolism and carbonyl stress in type 1 diabetes mellitus (T1DM) patients with different levels of albuminuria.

Materials and methods. 56 men of reproductive age with T1DM were divided into two groups: 24 patients with stage A1 albuminuria (group A1) and 32 patients with stage A2 albuminuria (group A2). The control group consisted of 28 healthy men. The levels of renal function markers, lipid metabolism parameters, and methylglyoxal were assessed using enzyme immunoassay and spectrophotometric and fluorometric methods.

Results. Higher values for total cholesterol, triacylglycerol, and very-low-density lipoprotein medians in both groups A1 and A2 were found. In these groups, increased podocalyxin and methylglyoxal medians were revealed. Correlation analysis in the group A1 showed the presence of a relationship between the glomerular filtration rate (GFR) and creatinine. In the group A2, correlations between the generally accepted parameters of kidney injury (the albumin / creatinine ratio and GFR) and the duration of the disease and between GFR and the creatinine and methylglyoxal levels in the blood were identified. The podocalyxin level in this group correlated with the β2- microglobulin and methylglyoxal levels and lipid metabolism parameters. The level of β2-microglobulin correlated with the lipid metabolism parameters.

Conclusion. Regardless of the level of albuminuria, men with T1DM had significantly increased levels of podocalyxin, lipid metabolism parameters, and methylglyoxal, as well as strong relationships between these parameters. The data of this study can be used for development of potential strategies for prevention and early treatment of diabetic nephropathy.

Post-COVID syndrome is characterized by fatigue, reduced exercise tolerance, muscle and joint pain, and psychoemotional disorders. In the development of a generalized body response in a viral infection, abnormal defense responses are of great importance. We studied neutrophils, neutrophil extracellular traps (NETs), DNA degradation products (purine nitrogenous bases, PNBs), and traditional biochemical parameters.

Aim. To determine biochemical parameters and the number of NETs and PNBs in the peripheral blood of patients with post-COVID syndrome.

Materials and methods. The study included outpatients (n = 21) aged 18–59 years (36 [27 ÷ 50]). The control group consisted of 20 individuals aged 18–59 years (38.5 [29 ÷ 51.5]) without a past medical history of the coronavirus infection. All patients underwent a physical examination, their medical history was assessed, and the level of NETs and PNBs in the venous blood was determined.

Results. 11 patients had a mild form of the disease in their past medical history, 7 – moderate, and 3 – severe. The most common symptoms in the patients were fatigue, headache, epigastric pain, dizziness, and joint pain. Hair loss and dyspnea were less common. The concentration of NETs and PNBs was higher in the patients with post-COVID syndrome than in the control group (p < 0.05). We detected NETs in the patients with post-COVID syndrome only in the form of filamentous structures. The concentration of extracellular purine bases in the blood of the patients with post-COVID syndrome was the highest in patients with moderate and severe acute periods. In patients with a mild acute period, the concentration of PNBs was 7.38 [0.0 ÷ 60.7] mg / ml, and in patients with moderate and severe acute periods – 19.15 [0.0 ÷ 33.5] and 34.19 [3.35 ÷ 70.0] mg / ml, respectively.

Conclusion. Extracellular purine bases in concentrations capable of causing secondary alteration of cells are found in the peripheral blood of patients with post-COVID syndrome. Post-COVID syndrome is accompanied by the formation of filamentous NETs in the blood of patients.

Aim. To compare the clinical efficacy and influence on interferon (IFN) production / sensing of drugs with immunemediated antiviral effects, which potentiate type 1 (T1) immune responses, in the treatment of acute respiratory infections (ARI) in patients with allergic rhinitis.

Materials and methods. 146 ARI patients with remission of seasonal allergic rhinitis were divided into 4 cohorts. In addition to symptomatic therapy, patients received either 2,000 IU of IFNγ in each nasal passage 5 times a day; or rectal suppositories containing 106 IU of IFN-α2b and antioxidants (AO) twice a day, and a gel with IFN-α2b and AO intranasally 3 times a day; or 400 mg of pidotimod per os twice a day; or 125 mg of tilorone per os on days 1, 2, 4, and 6. The severity of ARI was determined daily as the sum of 10-point scores for 15 symptoms. Serum concentrations of IFNα and IFNγ and the ability of blood cells to produce these cytokines ex vivo spontaneously and upon stimulation with Newcastle disease virus or phytohemagglutinin were studied using enzyme-linked immunosorbent assay (ELISA). The proportions of circulating lymphocytes expressing type I IFN receptor subunit 2 (CD118) or IFNγ receptor α-chain (CD119) were determined by flow cytometry.

Results. ARI symptoms in all cohorts generally regressed in a similar way. However, from day 5 of the treatment, pidotimod relieved symptoms more effectively than other drugs. In patients treated with tilorone, the regression of ARI manifestations was delayed in the first two to three days, followed by rapid symptom reduction. An initial decrease in the induced production of IFNγ was found in patients treated with pidotimod, and a tendency to a decrease in this parameter was noted in other cohorts. The induced production of IFNγ after the treatment in all groups did not differ from that in healthy donors. No significant changes and differences in the proportions of CD118+ and CD119+ lymphocytes were found between the cohorts, except for a decrease in the number of CD118+ cells after the treatment with tilorone. In patients treated with IFN-α2b + AO, the proportions of CD119+ and CD118+ lymphocytes tended to increase slightly.

Conclusion. Drugs that promote the development of T1 over T2 immune responses are a useful option for treating ARI in patients with allergic rhinitis.

The aim. To study the toxicity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in vitro and in vivo.

Materials and methods. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was synthesized using a method for expanding the o-quinone cycle during the reaction between 5-nitro-2,6,8-trimethyl4-chloroquinoline and 3,4,5,6-tetrachloro-1,2-benzoquinone while boiled in dioxane. An in vitro experiment was carried out in the human A549 cell line. Cell viability was assessed using the MTT colorimetric assay by reducing the optical density of the experimental samples compared with the control ones. Acute toxicity was studied on 20 BALB/c Nude male mice. The test compound was administered once orally as a suspension in 1% starch gel at three doses: 0.0055 (group 1), 0.055 (group 2) and 0.55 mg / g (group 3). The control group (group 4) received a placebo.

Results. We synthesized a new compound, 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone. Its structure was established by 1 H nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry. The yield was 19.8 g (52%), the melting point was 205–207 ºС, bright yellow crystals (benzene) were observed. The half-maximal inhibitory concentration (IC50) of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was 0.21 ± 0.01 μM, which was significantly lower (р < 0.05) than the IC50 of cisplatin (3.84 ± 0.23). Following the in vivo experiment, no toxic effect of tropolone was detected when administered once at a dose of 0.0055, 0.055, and 0.55 mg / g.

Conclusion. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated cytotoxic effects on the A549 cell line at a lower IC50 than cisplatin which is widely used in treatment of cancers, including lung cancer. Insolubility of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in water and the absence of its toxic effect in the studied modes determine the scope of its application for further study of cumulative and antitumor effects.

Aim. To improve the efficiency of diagnosis of hereditary lysosomal storage diseases using an intelligent computerbased decision support system.

Materials and methods. Descriptions of 35 clinical cases from the literature and depersonalized data of 52 patients from electronic health records were used as material for clinical testing of the computer diagnostic system. Knowledge engineering techniques have been used to extract, structure, and formalize knowledge from texts and experts. Literary sources included online databases and publications (in Russian and English). On this basis, for each clinical form of lysosomal diseases, textological cards were created, the information in which was corrected by experts. Then matrices were formed, including certainty factors (coefficients) for the manifestation, severity, and relevance of signs for each age group (up to 1 year, from 1 to 3 years inclusive, from 4 to 6 years inclusive, 7 years and older). The knowledge base of the expert system was implemented on the ontology network and included a disease model with reference variants of clinical forms. Decision making was carried out using production rules.

Results. The expert computer system was developed to support clinical decision-making at the pre-laboratory stage of differential diagnosis of lysosomal storage diseases. The result of its operation was a ranked list of hypotheses, reflecting the degree of their compliance with reference descriptions of clinical disease forms in the knowledge base. Clinical testing was carried out on cases from literary sources and patient data from electronic health records. The criterion for assessing the effectiveness of disease recognition was inclusion of the verified diagnosis in the list of five hypotheses generated by the system. Based on the testing results, the accuracy was 87.4%.

Conclusion. The expert system for the diagnosis of hereditary diseases has shown fairly high efficiency at the stage of compiling a differential diagnosis list at the pre-laboratory stage, which allows us to speak about the possibility of its use in clinical practice.

Aim. To investigate the relationship between the expression of Ca2+ handling proteins of the sarcoplasmic reticulum, polymorphic variants of their genes, and structural and functional parameters of the heart in patients with atrial fibrillation (AF).

Materials and methods. The study included patients with AF. The patients underwent radiofrequency ablation, during which a myocardial biopsy was taken. The patients underwent echocardiography (EchoCG) before surgery. Polymorphic variants rs1860561 of the ATP2A2 gene and rs6684209 and rs7521023 of the CASQ2 gene were determined in the patients by real-time polymerase chain reaction (PCR), and the level of expression of SERCA2a and CASQ2 proteins in the myocardium was detected by immunoblotting.

Results. Carriers of the GG genotype at rs1860561 of the ATP2A2 gene and CC genotype at rs6684209 of the CASQ2 gene were characterized by significantly higher expression of the corresponding proteins. Using cluster analysis, we identified groups of patients by the level of SERCA2a and CASQ2 expression: group 1 – patients with low protein content; group 2 – patients with high protein content. According to clinical and anamnestic parameters, the patients in the selected groups were homogeneous. In patients with high SERCA2a levels, the end systolic and diastolic volumes of the left ventricle (LV) were significantly higher than those in patients with low levels of this protein. The rates of early (peak E) and late left ventricular diastolic filling (peak A) were significantly lower in the group with high SERCA2a expression. A comparative analysis of EchoCG data of patients distributed by the level of CASQ2 expression in the myocardium did not reveal significant differences between the groups.

Conclusion. The polymorphic variant rs1860561 of the ATP2A2 gene and rs6684209 of the CASQ2 gene can modulate the level of SERCA2a and CASQ2 expression. SERCA2a expression is associated with the functional and structural parameters of the heart in patients with AF.

Aim. To evaluate the relationship between nutrition and the risk of fatal outcomes from cardiovascular diseases in individuals with type 2 diabetes mellitus (T2DM).

Materials and methods. The baseline study was conducted within the HAPIEE project in 2002–2005. The followup period for the observed cohort, including individuals with T2DM, lasted from 2003–2005 to December 31, 2018 and reached on average 12.8 years (1.1 ± 16.0 years). Within the study, 2 groups were formed: the treatment group which included persons with T2DM who “developed fatal events” and the control group which encompassed individuals with T2DM who “did not develop fatal events” during the follow-up. The treatment group included 207 people (107 men, 100 women), the average age for both sexes was 62.4 ± 5.9 years; the control group consisted of 474 people (177 men, 297 women), the average age for both sexes was 58.1 ± 6.6 years. The data on actual nutrition were obtained from a survey of the participants using the Food Frequency Questionnaire and included information on consumption of 147 foods. Statistical processing of the data was carried out using the SPSS 13.0 software package. The data were presented as M ± SD, where M is the arithmetic mean and SD is the standard deviation. An analysis of the association between nutrition and the risk of death from cardiovascular diseases was performed using the Cox regression model. The differences were considered statistically significant at p < 0.05.

Results. In the studied sample, we identified a significant relationship between the consumption of a number of foods and the risk of death from cardiovascular diseases in people with T2DM over a 15-year follow-up. It was shown that increased consumption of fruits (by 80 g / day) and nuts (by 2 g / day) was significantly associated with a decreased risk of death in men: hazard ratio (HR) = 0.726, p = 0.044 and HR = 0.826, p = 0.011, respectively. Increased consumption of eggs in men (by 50 g / day) was associated with an increased risk of death: HR = 1.728, p = 0.003. In women, a decreased risk of death was observed only with the consumption of meat products: HR = 0.786, p = 0.036.

Conclusion. The results of the study showed a clear relationship between the consumption of a number of foods and the risk of death from cardiovascular diseases. Thus, increased consumption of fruits, nuts, and meat products was significantly associated with a decreased risk of death from cardiovascular diseases in people with T2DM, while the consumption of eggs and dairy products, on the contrary, was associated with an increased risk of mortality. These data indicate the importance of dietary control in individuals with carbohydrate metabolism disorders.

Aim. To evaluate the functional state of mitochondria isolated from peripheral blood mononuclear leukocytes using flow cytometry in patients with chronic heart failure receiving ubidecarenone (coenzyme Q).

Materials and methods. The study included 53 patients with chronic heart failure who had experienced myocardial infarction. The patients were divided into two groups: group 1 received optimally chosen standard therapy, while group 2 received optimally chosen standard therapy and ubidecarenone (“Kudevite”). The mitochondrial membrane potential was evaluated by flow cytometry using propidium iodide and 3,3′-dihexyloxacarbocyanine iodide (DiOC6(3)). The levels of coenzyme Q were determined using high-performance liquid chromatography with ultraviolet (UV) detection.

Results. A direct correlation was established between the coenzyme Q levels in the blood plasma and the percentage of DiOC6(3)-positive cells (R = 0.39; р < 0.05) in the patients with chronic heart failure. In group 1, no significant differences in the coenzyme Q levels and the percentage of DiOC6(3)-positive and DiOC6(3)-negative cells before and after the therapy were observed. In group 2, a significant increase in the proportion of DiOC6(3)-positive cells and a significant decrease in the percentage of DiOC6(3)-negative cells were revealed.

Conclusion. The increase in the functional activity of mitochondria in the patients with chronic heart failure receiving ubidecarenone was identified. Flow cytometry can be used to evaluate the functional state of mitochondria and observe the efficiency of the selected therapy.

Acellular dermal matrices (ADMs) are gaining popularity as surgical materials for operations on the pelvic organs, as well as in burn therapy and plastic surgery. Evaluation of the biocompatibility of surgical materials is an important and necessary step in the development of new ADMs.

The aim of the study was to compare the results of subcutaneous implantation of ADM and native porcine skin in rats.

Materials and methods. To obtain ADMs, detergent – enzymatic decellularization was used. On days 7, 14, 21, and 60 after the implantation of ADMs (the experimental group) and native porcine skin (the control group), the animals were removed from the experiment. The histologic sections were stained with hematoxylin – eosin and Masson’s trichrome stain, then an immunohistochemical reaction with antibodies to CD3 and CD68 was performed. Computer morphometry was carried out using the ImageJ software.

Results. On day 7 after the implantation, moderate sterile inflammation in the experimental group and pronounced sterile inflammation with eosinophil infiltration in the control group were observed. On day 14 of the experiment, the samples from the experimental group were characterized by a relatively low content of macrophages and T-lymphocytes with insignificant edema and no signs of ADM biodegradation. The control group showed pronounced inflammation, a large number of infiltrating macrophages and T lymphocytes, as well as fragmentation of collagen fibers. On day 21 of the experiment, a thin capsule was formed around ADM, there was a small number of infiltrating T lymphocytes and macrophages, the collagen fibers of the implant were intact. In the samples of the control group, there was pronounced inflammation with the presence of a significant number of lymphocytes and macrophages, as well as fragmentation and vascularization of the implant. On day 60 of the experiment, no inflammatory response was observed around ADM, biodegradation was minimal, and a dense fibrous capsule was formed around the fragment of the native porcine skin.

Conclusion. The experimental ADM has low immunogenicity and a low degree of biodegradation, which makes it possible to use it for further research to create efficient surgical material that is safe for use in clinical practice.

Aim. To assess the possibility of combined application of screening methods for early detection of risks of bipolar disorder in adolescents.

Materials and methods. The study included 139 adolescents aged 13–16 years. A clinical psychopathology assessment as well as screening methods were used. The screening methods included the Bipolar Spectrum Diagnostic Scale ((BSDS), R. Pies, 2005) and the Mood Disorder Questionnaire ((MDQ), R.M. Hirschfeld, 2000).

Results. The clinical psychopathology assessment was performed in accordance with criteria of ICD-10, Class V. No mental and behavioral disorders (F00-F99), including affective pathology, were identified. Following the MDQ screening, the risk of bipolar disorder was revealed in 63 individuals (45.3%; 95 % confidence interval (CI): (36.8–53.9). When the BSDS method was used, the risk of bipolar disorder was revealed in 16.2% of cases (CI: (11.9–28.3)). The combined use of the screening scales (MDQ and BSDS) confirmed their consistency in detecting values both not exceeding (48.7% of the cases) and exceeding the threshold rates (17.1% of the cases).

Conclusion. Early diagnosis of a risk of bipolar disorder in adolescents, along with a clinical psychopathology assessment, may include application of screening scales. Сombined use of several screening methods is justified by polymorphism of initial hypomanic and depressive states, as well as by difficulties in subjective assessment of symptoms of bipolar disorder in adolescents.

Aim. To assess the relationship between the activity of systemic inflammation and the hemoglobin level in patients with spondyloarthritis (SpA).

Materials and methods. We examined 92 patients with SpA aged 42.9 ± 11.6 years (SpA duration – 14.8 ± 9.6 years, 55 (60%) men). We calculated the BASDAI and ASDAS-CRP scores, performed complete blood count, evaluated erythrocyte sedimentation rate (ESR), ferrokinetic parameters, C-reactive protein (CRP) level, and serum concentrations of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6).

Results. Anemia was found in 52 (57%) patients: 13 (25%) patients were diagnosed with anemia of inflammation (AI), 39 (75%) individuals had a combination of AI and iron deficiency anemia. A significant increase in CRP (17.8 vs. 9.0 mg / l, respectively; p = 0.001) and ESR (23 vs. 10 mm / h, p < 0.001), a tendency toward an increase in IL-6 levels (5.4 vs. 4.1 pg / ml, p = 0.051), and no difference in TNF-α levels (3.4 vs. 3.0 pg / ml, p = 0.245) were revealed in patients with anemia compared with patients with normal hemoglobin level. The hemoglobin concentration was negatively correlated with the CRP level (r = –0.327, p = 0.001) and ESR (r = –0.527, p < 0.001). IL-6 was positively correlated with the levels of TNF-a, CRP, and ESR (r = 0.431, r = 0.361, r = 0.369; all p < 0.001). With the IL-6 concentration >10 pg / ml, the odds for anemia were 5.3 times higher (95% confidence interval: 1.4–19.9, p = 0.009).

Conclusion. The relationship between the activity of systemic inflammation and anemia in patients with SpA was confirmed. Taking into account the pathogenesis of AI, the aim of antianemic treatment is to achieve remission or minimal activity of SpA. Additional studies are required to determine the effect of anti-inflammatory therapy on the development and course of anemia in patients with SpA.

Aim. To compare the effect of increased concentrations of aggregation inducers (five-fold addition) under standard conditions and under the conditions of vortex flow in vitro on platelet aggregation in patients with chronic heart failure (CHF).

Materials and methods. The study included 28 patients. The activity of platelet aggregation in platelet-rich plasma (PRP) was evaluated according to light transmission curves (%) and the average size of aggregates (relative units (rel. units)). The aggregation inducer was added once at 10 seconds of the study (standard procedure) and five times at 10 seconds, 1, 2, 3, and 4 minutes of the study with a constant stirring rate of 800 rpm. The same parameters were evaluated under the conditions of vortex flow, which was created by changing the stirring rate of the PRP from 800 rpm to 0 rpm and again to 800 rpm by pressing the centrifugation button on the analyzer.

Results. In the course of the study, the size of the aggregates increased in patients with CHF only under the conditions of vortex flow. When a collagen aggregation inducer was added both at the concentration of 2 mmol / l and 10 mmol / l, platelet aggregation parameters increased under the conditions of vortex flow. During the study of epinephrine-induced platelet aggregation in patients with CHF, an increase in the aggregation parameters was revealed, both at five-fold addition of the inducer and under the conditions of vortex flow compared with the standard method.

Conclusion. The proposed methodological approaches to creating the conditions for vortex flow in vitro and to five-fold addition of epinephrine showed an increase in the size of the aggregates and the degree of platelet aggregation. Collagen-induced aggregation under the conditions of vortex flow revealed 7 (25%) patients with high residual platelet reactivity (HRPR), and epinephrine-induced aggregation detected 15 (54%) patients with HRPR.

Aim. To investigate the content of insulin-like growth factor (IGF)-1, IGF-2, and their transporter proteins IGFBP-1 and IGFBP in the liver of rats with experimental diabetes, Guerin’s carcinoma, and their combination.

Materials and methods. The experiment was carried out on 64 white outbred rats of both sexes, which were divided into 4 groups of 8 animals each: group 1 – intact animals, group 2 – animals with experimental diabetes, group 3 – animals with subcutaneously inoculated Guerin’s carcinoma, group 4 – animals with experimental diabetes and subcutaneously inoculated Guerin’s carcinoma. In the study, biochemical and statistical analyses and enzyme immunoassays were performed.

Results. In the liver of the outbred rats, sex specificity in the content of insulin-like growth factors and IGFBP-1 was established: the levels of IGF-1, IGF-2, and IGFBP-1 in males were lower than in females. It was shown that the development of diabetes mellitus and the growth of Guerin’s carcinoma led to changes in the sex-specific components in the rat liver.

Conclusion. The growth of Guerin’s carcinoma and the progression of diabetes mellitus cause multidirectional changes in IGF and IGFBP levels in the liver of females and unidirectional changes in the liver of males. Following the growth of Guerin’s carcinoma against the background of diabetes mellitus, sex-specific differences in the content of the studied parameters were minimized. It was shown that diabetes mellitus changed the metabolic profile of the liver in the animals of both sexes.

Aim. To study the state of microcirculation and metabolic activity of the soft tissues in the compression area in experimental crush injury after local hyaluronic acid injection and to determine the effective mode of its application.

Materials and methods. The experiments were carried out on 178 male Wistar rats aged 4–4.5 months and weighing 280–340 g. The study design included anesthesia, modeling of crush injury (CI), local injection of 1.75% hyaluronic acid (HA) solution into the compression area, systemic intravenous injection of 0.9% sodium chloride solution daily for 3 days, and a study of microcirculation and metabolism of the soft tissues in the damaged area 3, 7, 14, and 28 days after the injury.

Results. Early (3 hours after the injury) local application of HA for CI improved microcirculation, increased oxygen consumption, and activated oxidative metabolism in the skeletal muscles, which helped reduce the severity of destructive processes in the damaged area. The most effective injection mode was two-fold administration of HA: 3 hours after the compression cessation and additionally 24 hours after the injury.

Conclusion. In the crush injury, early local intramuscular injection of HA into the damaged area in the first few hours after the cessation of compression is a sanogenetically substantiated method for correcting traumatic ischemia of the muscles.

Community-acquired pneumonia remains the leading infectious cause of death around the world. Many factors influence the prognosis and outcome of this disease. Compared with healthy individuals, patients with diabetes mellitus are at increased risk of respiratory tract infections, such as community-acquired pneumonia. Diabetes mellitus contributes to the development of pulmonary thrombotic microangiopathy, changing the functional state of the lungs. In numerous studies involving patients with diabetes mellitus, data on the state of the lungs were obtained by instrumental tests, such as spirometry, ventilation / perfusion scintigraphy, perfusion computed tomography, and diffusing capacity of the lungs for carbon monoxide. In patients with community-acquired pneumonia, diabetes mellitus causes vague clinical symptoms, leads to a severe course of the disease, and contributes to development of complications. Diagnosing the functional state of the lungs in patients with community-acquired pneumonia against the background of diabetes mellitus has not been studied.

The authors analyzed the problem of diuretic resistance (DR) in patients with chronic heart failure (CHF). Most of the symptoms and signs of CHF are associated with hypervolemia and vascular congestion in the systemic and pulmonary circulation. The severity of the latter is the main factor which negatively affects the overall assessment of life satisfaction in patients with CHF. Since the patient, even at the incurable stage of CHF, primarily expects a rapid decrease in the severity of manifestations of decompensation from the prescribed therapy, achieving euvolemia is the essence of its short-term objective. Without diuretics, these immediate effects, according to which most CHF patients judge the qualifications of the doctor, are almost impossible to achieve. Unfortunately, apparently, not a single clinician was able to avoid disappointment in the effectiveness of CHF therapy associated with DR in their practice. As a rule, DR reflects the progressive course of CHF and is often associated with a poor prognosis. The review consistently covers the issues of terminology, diagnosis, pathogenesis, and prevention of DR, which aggravates CHF, and discusses measures aimed at restoring sensitivity to diuretics.

The review focuses on allergen-specific immunotherapy (AIT), a treatment method for atopic diseases, including allergic rhinitis. The theoretical and practical basics, development prospects, indications and contraindications to AIT, peculiarities of AIT execution in allergic rhinitis, and tolerogenic effects of immunotherapy are considered. Advantages and disadvantages of each of the two preferable routes of allergen administration in AIT, subcutaneous and sublingual, are described. The main goals of further AIT advancement include shortening of treatment protocols with no significant loss of efficacy, creation of a safer adverse effect profile, and distribution of AIT in developing countries.

The review is devoted to the consideration of the history of paradigms in the study of depressive disorders in terms of modern understanding of depression in psychiatry and clinical and medical psychology and its correlation with the biopsychosocial model in medicine. The review also contains works devoted to the study of the prevalence and comorbidity of depressive disorders and their relationship with suicidal behavior. The existing limitations in the study of depressive disorders in psychiatry and clinical psychology and the issues of interdisciplinary integration and interdisciplinary barriers are considered in detail. The review includes publications indexed in the Web of Science, Scopus, Russian Science Citation Index, and PubMed databases. Depression is a major medical and psychological problem due to its widespread prevalence in the general population, in primary care, among patients with various chronic somatic symptom disorders who receive treatment in community and specialized hospitals and clinics, and among clients of psychological centers and social services. In 1996, the Harvard T.H. Chan School of Public Health, based on the materials of the World Health Organization (WHO) and the World Bank, published estimates and prognosis for the prevalence of depressive disorders around the world. According to their data, depression in 1990 was ranked 4^th in terms of the severity of the leading causes of the burden of the disease, and according to the baseline scenario of development, by 2020 it should have been ranked 2^nd after coronary artery disease. The review is focused on the need to revise the baseline scenario of development and start a new discussion on the study of depressive disorders under new conditions, such as the psychological state of society during the COVID-19 pandemic and lockdown, as well as on the eve of healthcare transition to the 11th Revision of the International Classification of Diseases.

Vascular aging plays a key role in morbidity and mortality in the elderly. With age, the vasculature undergoes changes characterized by endothelial dysfunction, wall thickening, decreased elongation, and arterial stiffness. The review focuses on the main cellular and molecular mechanisms of aging, including oxidative stress, endothelial dysfunction, inflammation, increased arterial stiffness, and molecular genetic aspects. Their role in the pathogenesis of diseases associated with aging is considered. Some of the molecular mechanisms underlying these processes include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor β1 signaling, increased levels of C-reactive protein, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)α, and N-terminal pro B-type natriuretic peptide (NT-pro-BNP), and activation of proinflammatory signaling pathways. These events can be caused by vasoactive agents, such as angiotensin II and endothelin-1, the levels of which increase with aging. For prevention of cardiovascular diseases, it is important to understand the mechanisms underlying age-related pathophysiological changes in the blood vessels.

An immune response to invasion of viral pathogens is an integral part of maintaining the physiological functioning of the bronchopulmonary system and effective gas exchange. Collagen-containing C-type lectins (lung collectins) are some of the key proteins in the identification of viral particles. They have image-recognizing receptors that identify pathogen-associated molecular patterns, particularly viral glycoproteins. The surfactant proteins SP-A and SP-D, which are composed of trimerized units, belong to pulmonary collectins and oligomerize into higher-order structures. These proteins play an essential role in recognition and elimination of microbial pathogens (viruses, bacteria, fungi, parasites, nanoparticles, allergens) through a variety of mechanisms. Taking into account the burden of the novel coronavirus infection caused by the SARS-CoV-2 virus, it is important to consider the role of the surfactant proteins SP-A and SP-D in the pathogenesis of the immune response to viral invasion. Currently, there are data on the direct relationship between surfactant proteins and viruses belonging to the Coronaviridae family. The SP-A and SP-D proteins modulate inflammatory responses and cytokine synthesis, but prevent an excessive inflammatory response (cytokine storm). There is also an assumption that SARSCoV-2 directly suppresses and alters the production of surfactant proteins. Thus, the key pathogenetic role of the surfactant proteins SP-A and SP-D in the response to the viral pathogen SARS-CoV-2 is evident. Today, this is a promising area of translational medicine, which will contribute to a profound understanding of the pathogenesis of coronavirus infection for assessing the diagnostic and prognostic potentials of the surfactant proteins SP-A and SP-D in COVID-19. Additionally, it will help evaluate the therapeutic potential of recombinant fragments of human SP-A and SP-D.

We presented a clinical case of the successful treatment of a severe course of polysegmental pneumonia caused by the novel coronavirus infection, that developed in the postoperative period after bariatric surgery in the patient with morbid obesity, comorbid type 2 diabetes mellitus, ischemic heart disease, arterial hypertension, pulmonary embolism (in past medical history), and stage 3 chronic obstructive pulmonary disease. The given clinical case demonstrates the possibility of successful treatment of coronavirus infection in the polymorbid patient at an extremely high risk of an unfavorable outcome, given timely diagnosis, combination therapy using drugs that block cytokine storm, and strict adherence to clinical recommendations.