ORIGINAL RESEARCH
I n t r o d u c t i o n. Data from clinical studies indicate that the most severe course of the novel coronavirus infection (NСI) caused by the SARS-CoV-2 virus is observed in people with obesity and associated metabolic and cardiovascular diseases, then, in elderly patients with comorbidities, the disease proceeds in an even more severe form.
A i m. To study the association of anthropometric and clinical laboratory parameters characterizing obesity with the course of the NСI in order to identify the most sensitive markers of the disease severity.
M a t e r i a l s a n d m e t h o d. 172 patients (men and women) aged from 33 to 86 years (mean age 62.2 ± 12.1 year) who were under inpatient treatment for the NСI in an infectious hospital during 2020–2021 were examined. The patients were divided into two groups: group 1, patients with the moderate course of the NСI (n = 127), and group 2, patients – with the severe (n = 45). There were no patients with the mild course of the NСI among those hospitalized. All patients underwent anthropometric, laboratory and clinical examinations, including echocardiographic assessment of the structural and functional parameters of the heart with the epicardial fat thickness (EFT) assessment.
R e s u l t s. In patients with severe NCI, the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score was significantly higher than in patients with moderate NСI (p < 0.05). Patients with the severe NCI also had more pronounced visceral obesity, as evidenced by statistically much higher values of such indicators as waist circumference (WC), the waist and hip circumference (WC/HC) ratio and EFT. A correlation analysis was performed to identify factors associated with the severity of the NCI. A number of statistically significant correlations (positive and negative) were identified between key indicators characterizing the severity of NCI and the factors affecting them. The largest number of correlations was identified with the EFT, which had a statistically significant direct correlation with the duration of hospitalization, levels of C-reactive protein, fibrinogen, as well as the volume of lung damage. A negative correlation was found with the levels of saturation, total protein and albumin. The number of correlations with EFT was almost 2 times higher than with other indicators, and the correlation strength was higher. EFT was followed by WC and the WC/HC ratio. In third place was the CIRS-G score.
C o n c l u s i o n. Visceral obesity is a predictor of the hospitalization duration and the NCI progression, and the EFT turned out to be the most sensitive marker of the severity of the studied infectious disease.
I n t r o d u c t i o n. Sodium benzoate is a preservative widely used in the food industry to increase the shelf life of food products. However, its genotoxic, hepatotoxic and nephrotoxic properties have been established, which requires further study of its effects on the body.
A i m. To study the effect of a 60-day exposure to sodium benzoate on the structure of the thyroid C-cells, the main parathyroid cells and the spongiocytes of the adrenal zona fasciculata, taking into account changes in the microstructure and phase composition of the biomineral of the regenerating tibias amid modeling a mechanical injury.
M a t e r i a l s a n d m e t h o d s. One hundred and twenty albino mature male rats were divided into four groups (30 animals in each group). Animals of groups 1 and 2 were exposed to sodium benzoate for 60 days at doses of 500 and 1000 mg/kg, after which a defect in the tibias was simulated. In group 3, instead of sodium benzoate, the animals were injected with saline solution. In group 4, rats received saline without simulating the tibial injury. The study of changes in the cytomorphometric parameters of the thyroid C-cells was carried out using electron microscopy on the 3rd and 24th days after defect modeling. The study of the morphometric parameters of the main parathyroid cells and spongiocytes of the adrenal zona fasciculata was carried out by light microscopy on days 3, 10, 15, 24, 45, and the indicators characterizing the microstructure and phase composition of the biomineral of the regenerating bones were studied by X-ray diffraction analysis at the same time points.
R e s u l t s. In group 1, the area occupied by euchromatin in the nuclei of C-cells significantly decreased compared to group 3 on the 24th day by 21.13%, and in group 2 on the 3rd and 24th day – by 5.83 and 16.29%. In groups 1 and 2, on the 3rd and 24th day, the ratio of euchromatin and heterochromatin areas was less by 2.65, 22.25 and 6.69, 17.69%, the diameter of secretory granules – by 7.47, 15.43 and 8.92, 16.00%. The number of nuclei of the main parathyroid cells per area unit decreased significantly only in group 2 from the 3rd to 24th day by 3.96, 3.34, 3.68%, and the functional activity index decreased on the 3rd day by 6.34%. The number of spongiocyte nuclei per area unit in the zona fasciculata decreased significantly in both groups from the 3rd to 45th day – by 2.87, 2.40 and 5.57, 3.91%. In the 1st group, the index of functional activity of spongiocytes was lower only from the 3rd to 15th day by 7.20, 6.78, 4.54%, and in the second group – in all time points by 10.73 and 7.23%. In the biomineral of the regenerating tibias in rats of group 1, a significant increase in the size of unit cells along the c axis was revealed on the 15th and 24th days by 0.23 and 0.17%. In group 2, the increase in the size of unit cells along the a axis was significant from the 15th to 45th day by 0.28, 0.15, 0.13%, and the increase in the size of the unit cells along the c axis was significant from the 10th to 45th day by 0.18, 0.23, 0.21, 0.12%. In same groups, a significant positive correlation was found between such parameters as the number of nuclei of the main parathyroid cells, spongiocytes of the zona fasciculata and the size of unit cells along the a, c axes, the percentage of whitlockite, and the correlation between the parameter “ratio of the areas of euchromatin and heterochromatin in the C-cell nuclei” was positive on the 3rd day and negative on the 24th day.
C o n c l u s i o n. The morphofunctional state of C-cells, main parathyroid cells and spongiocytes of the zona fasciculata is dose-dependently inhibited by the previous 60-day administration of sodium benzoate. This is accompanied by alteration of compensatory and restorative processes during reparative osteogenesis. Using the correlation analysis, relationships of varying strength and direction were found between changes in the morphometric parameters of the endocrine glands and the microstructure of the regenerating bones.
I n t r o d u c t i o n. The main parameters of a person’s physical development are body height and weight, but for a comprehensive assessment it is necessary to take into account other parameters of the human body one of which is cephalometric ones. Of particular interest is the assessment of cephalometric parameters in correlation with somatotype and physical activity of an individual.
A i m. To assess the main cephalometric parameters of adolescents and young men in the Altai territory taking into account their somatotype and physical activity.
M a t e r i a l s a n d m e t h o d s. A somatometric study of adolescents and young men including the measurement of head sizes was performed. The study cohort was represented by Caucasian males aged 14 to 19 years. A total of 1186 people took part in the study. The young men were divided into 6 age groups with an interval of 1 year, starting with a group of 14-year-old adolescents and ending with a group of 19-year-old young men. Additionally, the groups were divided into subgroups based on physical activity. The first subgroup includes adolescents and young men who meet the general hygienic standard for physical activity according to the classification of A.G. Sukharev. The second subgroup includes adolescents and young men who exceed this hygienic standard.
R e s u l t s. The majority of adolescents were ectomorphs with a narrow, mesocephalic head shape and medium head height. The majority of young men were mesomorphs with a narrow head of average height.
C o n c l u s i o n. The results of the study in groups of adolescents and young men living in the Altai territory show the heterogeneity in the groups. An increase in head circumference in individuals with moderate physical activity compared to individuals with high physical activity is observed at the age of 14 and 16 years.
I n t r o d u c t i o n. Testicular hyaluronidase preparations are widely used in medical practice. Modification of native biologically active molecules by electron beam PEGylation allows to improve their pharmacokinetic properties, which determines a subsequent improvement of pharmacodynamic effects. The development of an original oral drug with a pharmacologically active core, which is hyaluronidase, is promising, but requires studying the safety of use at the preclinical stage.
A i m. Ultrastructural evaluation of hepatotoxic effects of PEGylated hyaluronidase in vitro.
M a t e r i a l s a n d m e t h o d s. The object of a study was testicular hyaluronidase PEGylated on polyethylene oxide (PEG-HYAL) using electron beam synthesis. The culture medium is a continous culture of human liver cells Chanq liver. The cytotoxic effect was detected by the MTT assay. Ultrastructural changes were evaluated by electron microscopy.
R e s u l t s. The original drug PEG-HYAL in the studied concentrations of 37, 75 and 150 U/ml has no cytotoxic effect on the human liver cell culture (hepatocytes). Cell viability is virtually at the control level when PEG-HYAL administration at concentrations of 37 and 75 U/ml, and in the maximum concentration of 150 U/ml, cell proliferation is stimulated significantly, as evidenced by an increase in cell viability up to 106%. The results of evaluation of ultrastructural changes in hepatocytes showed that exposure to PEG-HYAL in all concentrations leads to the enhancement of metabolic processes in cells, development of autophagy, which is one of the main homeostatic processes.
C o n c l u s i o n. The drug PEG-HYAL in all studied concentrations has no toxic effect on the human hepatocyte culture. The results obtained can be used in further research in the development of PEG-HYAL.
I n t r o d u c t i o n. The balance of estrogens and progesterone ensures the harmonious development of the uterus during pregnancy: progesterone provides an increase in the number of myocytes, and estrogens – their volume. Hormonal balance achieved through the catabolism of estrogens in the liver plays an important role in postpartum uterine involution. In this regard, liver diseases during pregnancy can disturb the elimination of estrogens, which leads to hyperestrogenism and problems with maintenance of pregnancy, and can also cause impaired uterine postpartum involution.
A i m. The study of the expression of estrogen and progesterone receptors in the myometrium of C57Bl/6 mice during pregnancy and the late postpartum period in acute CCl4-induced hepatosis and in its correction with immobilized hyaluronidase (IH).
M a t e r i a l s a n d m e t h o d s. The experiment was performed on 100 female C57Bl/6 mice. Acute hepatosis was induced on the 13th day of pregnancy by a single intraperitoneal injection of a 50% carbon tetrachloride solution in olive oil at a dose of 0.3 ml/kg. The mice were divided into four groups: group 1 (control) – intact pregnant mice; group 2 – mice with acute toxic hepatosis; group 3 – pregnant mice with induced acute toxic hepatosis and its correction with IH on the 14th day of pregnancy; group 4 – intact pregnant mice receiving IH on the 14th day of pregnancy. In all groups, sampling was carried out on the 18th and 21st days of pregnancy and on the 1st, 10th and 15th days after parturition. The numerical density (Nai) of positively stained nuclei of the receptors in the test area in myocytes was calculated, regardless of the staining intensity.
R e s u l t s. During pregnancy in acute CCl4-induced hepatosis, the expression of progesterone and estrogen receptors in the myometrium does not change and corresponds to that of intact pregnant mice. In animals with acute CCl4-induced hepatosis, in the late postpartum period (up to 15 days), an increased expression of estrogen receptors in the myometrium is noted, with relatively stable expression rates of progesterone. In the correction of acute CCl4-induced hepatosis with IH, the expression of estrogen receptors in the postpartum period decreases and generally corresponds to similar indicators in intact pregnant mice.
C o n c l u s i o n. In acute CCl4-induced hepatosis, the balance of estrogen and progesterone receptors in the myometrium in the postpartum period is disturbed. In the correction of acute CCl4-induced hepatosis with IH, the levels of expression of estrogen and progesterone receptors in the myometrium are normalized which contributes to the completion of postpartum uterine involution.
I n t r o d u c t i o n. Alzheimer’s disease (AD) is one of the most common dementia disorders with an alarming rate of spread. The significant medical, social and economic burden of this disease makes it necessary to develop new agents for its treatment. In this case, the action of these agents can be focused on specific pathophysiological mechanisms of the disease, for example, apoptosis.
A i m. To study the effect of new monocarbonyl curcumin analogues on the change in the apoptotic response in rat brain under experimental AD.
M a t e r i a l s a n d m e t h o d s. AD was simulated in female Wistar rats by injecting beta-amyloid aggregates (1-42) into the CA1 region of the hippocampus. The studied compounds (1E, 4E)-1,5-bis (3,4,5-trimethoxyphenyl) penta-1,4-dien-3-one (code named AZBAX4) and (1E, 4E)-1,5-bis (2,4,6-trimethoxyphenyl) penta-1,4-dien-3-one (code named AZBAX6) at doses of 20 mg/kg (orally) each compound and the reference drug, donepezil at a dose of 50 mg/kg (orally) were administered for 30 days from the start of pathology modeling. Thereafter, samples of the hippocampus and cerebral cortex were collected from the animals for assessment of the concentration of apoptosis-related biomarkers: cytochrome c, apoptosis-inducing factor, caspase-3 and PUMA protein.
R e s u l t s. The administration of AZBAX4 and AZBAX6 compounds, as well as of the reference drug, contributed to a significant decrease in the concentration of proapoptotic biomarkers both in the hippocampus and cerebral cortex. The concentration of biomarkers of the intrinsic pathway of apoptosis (apoptosis-inducing factor and cytochrome c) was significantly (p < 0.05) lower in animals treated with AZBAX4 compared to rats treated with AZBAX6 and donepezil.
C o n c l u s i o n. The present study showed the relevance of further investigation of (1E, 4E)-1,5-bis (3,4,5-trimethoxyphenyl) penta-1,4-dien-3-one as an anti-apoptotic agent for therapy of AD.
I n t r o d u c t i o n. The development of a novel coronavirus infection (COVID-19) is not limited to respiratory damage. Adverse outcomes in patients with COVID-19 may be associated with cardiac damage.
A i m. Study of the structural changes in the myocardium and the molecular biological characteristics of the endothelium of blood capillaries in severe forms of COVID-19.
M a t e r i a l s a n d m e t h o d s. An analysis of the medical documentation – inpatient records of 73 deceased with bilateral multisegmental viral pneumonia caused by the SARS-CoV-2 virus, as well as data from 43 autopsies of patients who died (sudden coronary death) between September 2020 to July 2021, was performed. An assessment of some clinical and laboratory data (degree of lung damage; levels of C-reactive protein, troponin I, D-dimer; left ventricular ejection fraction, etc.), structural changes in the myocardium and molecular biological characteristics (CD31, CD34) of the endothelium of blood capillaries in severe forms of COVID-19 was carried out.
R e s u l t s. The analysis of clinical and laboratory data has shown that a decrease in myocardial contractility in severe forms of COVID-19 due to an extensive lung damage was accompanied by an increase in the level of C-reactive protein, D-dimer, troponin I and indicated acute myocardial damage. According to electrocardiography (ECG) monitoring and echocardiography, repolarization disorders and a decrease in myocardial contractility were noted, which was accompanied by a decrease in ejection fraction by 32%. In more than 70% of cases, various arrhythmic disorders (atrial fibrillation, etc.) were observed during ECG.
Light microscopy revealed the presence of sludge phenomenon, as well as swelling, desquamation and proliferation of the endothelium of blood capillaries, formation of diapedetic and focal hemorrhages, in some places leukocyte margination and their migration beyond vascular bed. Fibrin masses were observed in the lumen of blood vessels. Polarization microscopy, along with contractures in cardiomyocytes, revealed groups of cells with myocytolysis and primary granularity. In all observations, lipofuscinosis of cardiomyocytes was detected. Immunohistochemical examination showed a marked decrease in the expression level of CD31 (PECAM-1) and CD34 proteins – markers of blood vessels.
C o n c l u s i o n. The performed clinical and morphological analysis in severe forms of COVID-19 allowed us to obtain new data on degenerative changes in the myocardium and the structure of endothelial cells of blood capillaries, which can be used as a basis for methodological approaches to studying the mechanisms of development of heart failure in a novel coronavirus infection.
I n t r o d u c t i o n. Improvements in the quality of diagnosis and early treatment of malignant neoplasms have led to a decrease in the mortality rate. However, chemotherapy-induced toxicity can cause late and long-term side effects, one of which is infertility. At the moment, the mechanisms of damage caused by the toxic effect of drugs designated for the treatment of hematologic malignancies have not been sufficiently studied.
A i m. To study the morphofunctional state of the endocrine apparatus of rat testicles after the administration of chemotherapeutic agents.
M a t e r i a l s a n d m e t h o d s. A case-control study on 50 Wistar rats aged 3 months weighing 270–300 g was performed. The control group (n = 10) consisted of rats which did not receive drugs for the treatment of hematologic malignancies, the experimental group (n = 40) comprised rats which were intraperitoneally administered cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone (СНОР regimen). Testosterone and luteinizing hormone levels in rats were measured by enzyme immunoassay. The weight of rat testicles was measured, and the testicular mass index was calculated, as well as morphometry of Leydig cells was performed.
R e s u l t s. After a twofold administration of chemotherapeutic drugs (СНОР regimen), on the 14th day, the rats of the experimental group showed a decrease in the weight and mass index of the testicles. Results of morphometry indicated a decrease in the number of endocrine cells, number of medium- and large-size Leydig cells, and an increase in the number of small forms of these cells. Concentration of testosterone in blood plasma decreased. By the 35th day, the studied parameters in the rats of the experimental group corresponded to the controls.
C o n c l u s i o n. A twofold administration of chemotherapeutic drugs (СНОР regimen) on 7th and 14th days in rats was accompanied by a decrease in testicular weight, degenerative and atrophic changes in islets of interstitial (Leydig) cells, and a decrease in testosterone concentration in blood plasma. By the 35th day of the experiment, compensatory and adaptive responses were developing, characterized by the restoration of testicular weight, an increase in the number of medium- and large-size endocrine cells and testosterone level in blood plasma.
I n t r o d u c t i o n. Plants of the genus Onosma are widely used in Asian folk medicine. The wide range of pharmacological effects of herbal medicines from these plants is due to the variety of biologically active compounds (BAC). At the same time, the widespread species of the genus Onosma in Russia – Onosma simplicissima L. – has been studied insufficiently.
A i m. A pharmacognostic study of Onosma simplicissima herb.
M a t e r i a l s a n d m e t h o d s. The object of the study was the aerial part of Onosma simplicissima L., collected during the flowering phase. Total extracts from the raw materials obtained using water-ethanol mixtures and 2% hydrochloric acid as extractants were used for qualitative and quantitative analysis of plant components using spectrophotometric and gravimetric methods. The micromorphology of leaves and flowers was studied using a Zeiss Axio Scope.A1 microscope.
R e s u l t s. The following BAC were detected and quantified in the raw materials: polysaccharides – 5.4%, polyflavane compounds – 3.2%, chlorophyll a – 0.46%, chlorophyll b – 0.29%, the sum of carotenoids and xanthophylls – 0.03%, flavonoids (in terms of rutin) – 0.98% and hydroxycinnamic acids (in terms of dicaffeoylquinic acid) – 0.34%.
During the microscopic analysis of leaf morphology, three types of trichomes were determined which can be used for identification of the raw materials.
C o n c l u s i o n. The presence of BAC with anti-inflammatory, antibacterial and regenerative effects indicates the needs for an elaborate study of Onosma simplicissima as a promising source of herbal raw materials.
I n t r o d u c t i o n. Pelvic inflammatory diseases are often accompanied by the development of chronic pelvic pain, infertility and pregnancy complications, therefore they are an important medical and social problem. In the site of inflammation in chronic salpingo-oophoritis (CSO), microcirculation disorders and tissue hypoxia develop. The treatment modalities that improve blood circulation in tissues have a pathogenic basis. The use of magnetic field and laser therapy, which has an effect due to infrared laser radiation and a magnetic field, seems promising. Physiotherapeutic effects modulate the phases of the immune response during inflammation, which is reflected in the dynamics of immunogram indicators.
A i m. Based on the determination of the inflammatory response markers, to evaluate the effect of comprehensive treatment of CSO using physiotherapy.
M a t e r i a l s a n d m e t h o d s. The treatment results of 60 patients with the exacerbation of CSO were assessed based on the analysis of clinical, laboratory and immunological parameters. The patients were divided into 2 groups: group 1 (n = 30) included women who received pharmacologic treatment and physiotherapy; group 2 (n = 30) included patients who received pharmacologic treatment alone. The pharmacologic treatment included antimicrobial therapy with third-generation cephalosporins for 7 days, nonsteroidal anti-inflammatory and antiallergic agents. The treatment of patients in group 1 was supplemented by a course of 10 sessions of magnetic field and laser therapy. The levels of interleukin-1β and interleukin-4 were determined by enzyme immunoassay on the 1st and 8th days from the disease onset.
R e s u l t s. The comprehensive treatment of CSO with the use of magnetic field and laser therapy leads to the relief of the main clinical manifestations and a decrease in spontaneous levels of pro-inflammatory cytokines in a shorter time.
C o n c l u s i o n. The use of magnetic field and laser therapy in the treatment of the CSO exacerbation is accompanied by a favorable course of the inflammatory response.
REVIEW
This review summarizes literature data on advanced axial spondyloarthritis (axSpA). In addition to the characteristic radiological manifestations, patients with advanced axSpA are characterized by sagittal imbalance and contracture-related deformities of the spine, which can potentially lead to disability, loss of working capacity and a decrease in the quality of life. Delayed diagnosis remains one of the reasons for advanced stage development. Despite the introduction of the ASAS criteria in 2009, diagnosis is delayed for several years worldwide. In this regard, attempts are being made to identify factors for delayed diagnosis, for example, female gender, young age of the disease onset, HLA-B27 negativity, presence of psoriasis, uveitis, etc., but there is still no unequivocal opinion on this issue. It is important to note that the subject of discussion is early diagnosis and early treatment; well-designed long-term studies are required to prove their positive impact on patients with axSpA. Based on the data on the importance of preserving working capacity and functional status in people of working and childbearing age suffering from axSpA, there is a question about the advisability of studying predictors of the formation of the advanced stage of the disease and, consequently, unfavorable functional outcomes. According to the literature, the most suitable candidates would be sclerostin, Dickkopf-1 (Dkk-1) and visfatin. The development of parameters associated with the possibility of using potential markers is required to formulate tactics for the management of patients with progression of spondyloarthritis into a disabling condition.