STUDY OF INDICATORS OF ANTIMICROBIAL RESISTANCE IN PATIENTS WITH ALLERGODERMATOSIS, СОMPLICATED BY STAPHYLOCOCCUS INFECTION, ACCORDING TO THE RESULTS OF TESTS WITH AUTOSTRAINS

The relevance of the study is due to the lack of data on the state of nonspecific cellular immunity in studies with sera and autostrains of S. aureus isolated from patients with allergic dermatoses, which would reflect the intensity of antimicrobial immunity in patients with allergic dermatoses, aggravated by staphylococcal infection, depending on the severity of dermatosis. The aim of the study was to determine and analyze the results of antimicrobial immunity indicators in patients with atopic dermatitis and true eczema, aggravated by staphylococcal infection, using sera and autostrains of S. aureus, depending on the severity of the disease. Material and methods. It was included 107 patients with different stage of the allergic dermatoses severity and control group of 15 healthy individuals to the research . The patients were divided into 3 groups in according to the severity of cutaneous process course. There were determined the basic indices of initial stages of phagocytosis and oxydepending bactericidal activity of the phagocytes. It was conducted the immunologic examinations using the autostrains patient from the locus morbi and standard strain S. aureus ATCC for the estimation of antimicrobial immunity. Results. Evaluation of phagocytosis indices in patients with allergodermatosеs showed a correlation between the severity of the disease course and the level of inhibition of the cellular level of nonspecific immunity. According to the results of studies using autostrains S. aureus, the most significant inhibition of phagocytosis (p ≤ 0,05), compared to the values of similar indicators in the control group of healthy individuals, it was found in the groups of patients with moderate and severe atopic dermatosis (AD) course, respectively: phagocytic activity (PhА) (78,1 ± 1,4) and (72,4 ± 1,4) and (71,7 ± 0,8) %; phagocytic number___ (PhN) (5,3 ± 0,2) and (4,3 ± 0,2) and (3,5 ± 0,1) absolute number (abs. num.); phagocytic index__ (PhI) (6,8 ± 0,2) and (6,2 ± 0,2) and (4,8 ± 0,1) abs. num.; phagocytic capacity (PhC) (30,3 ± 1,0) and (26,5 ± 1,8) and (22,6 ± 0,8) ×103 microbial cell /mm3; spontaneous test of the renovation of nitroblue tetrazolium (sNBT) (42,1 ± 1,3) and (48,1 ± 1,2) and (50,6 ± 0,3) %; induction test of the renovation of nitroblue tetrazolium (іNBT) (63,4 ± 1,6) and (53,4 ± 0,8) and (51,7 ± 0,7) %. In the patients with true eczema (TE), they revealed a similar regularity of phagocytosis inhibition, most pronounced in patients with a severe disease course (p ≤ 0,05), but with a slightly smaller degree of difference between the indicator values of phagocytosis compared with the group of healthy individuals, respectively: PhА (74,8 ± 1,3) and (78,1 ± 1,4) %; PhN (4,5 ± 0,1) and (5,3 ± 0,2) abs. num.; PhI (5,9 ± 0,2) and (6,8 ± 0,9) abs. num.; sНСТ (46,0 ± 0,6) and (42,1 ± 1,3) %; іНСТ (51,8 ± 0,8) and (63,4 ± 1,6) %. Conclusions. The results of identification of phagocytosis in patients with allergodermatosеs using the standard culture of S. aureus ATCC 25923 generally reflect the described regularities of inhibition in patients of the cellular level of nonspecific immunity, but are less presentable for their identification in comparison with the autostrains. Keywords: allergic dermatoses, severity of the course, S aureus autostrains, S. aureus ATCC 25923, antimicrobial resistance.

STUDY OF VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p < 0.001) and 2.6 times more often than PFE (c2 = 31.5; p < 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p < 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p < 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p < 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p < 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.

DOSE-DEPENDENT EFFECTS OF LEVOTHYROXINE IN HEART FAILURE IN PATIENTS WITH CONCOMITANT THYROID PATHOLOGY

Currently, the use of thyroid hormones in the setting of heart failure (HF) is still an "open book". There are several unanswered questions: the regimen, doses and schedule of drug use, as well as the consequences of such therapy. Large clinical studies can provide information on the effect of these hormones on the long-term prognosis in patients with heart failure. At the same time, the presence of comorbid thyroid pathology, which requires the prescription of levothyroxine (LT), makes it possible to partially answer these questions. The aim is to study of the dose-dependent effect of LT on the course of HF in patients with autoimmune thyroiditis (AIT). Material and methods. The study included 218 patients with HF on the background of post-infarction cardiosclerosis. 109 (50.0 %) patients with AIT received LT due to hypothyreosis in the past. These patients intake LT during 2 years before included in the study and have euthyreosis. Whether the levels of thyroid stimulating hormone (TSH), free triiodthyronine (FT3) and free thyroxine (FT4) were determined. Results. Patients who used LT, comparing with patients without this drug, had smaller end-diastolic diametr (EDD) and end-systolic diametr (ESD) and end-diastolic volum (EDV) and end-systolic volum (ESV) of left ventricle (LV) and 22.9 % greater LV ejection fraction (EF) (+ 22.9 %, p = 0.0001), as well as higher low serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level (- 26.3 %, p = 0.009). In the subgroup of patients taking LT at a dose of 0.1 to 0.69 μg/kg, ejection fraction of left ventricle (LVEF) did not differ from patients without this tritment. At a dose of 0.7-1.19 μg/kg, LVEF is higher compared with that of patients who did not take LT (+ 37.9 %, p = 0.0001) and patients who took LT at a dose 0.1 - 0.33 μg/kg (+ 36.9 %, p = 0.0001). LVEF was the highest in patients taking LT at a dose of > 1.20 μg/kg. The use of LT for 2 years reduces the risk of re-hospitalization (RH) due to decompensation of heart failure (Odds ratio = 0.490 (0.281-0.857), p = 0.018) and a tendentious decrease in the risk of combined endpiont achieving (- 27.9 %, p = 0.074). The ROC analysis showed that the risk of RH in patients with heart failure due to decompensation of the disease decreases with the use of LT at a dose of > 0.53 μg/kg (sensitivity – 56.62 %, specificity – 60.98 %, p = 0.016). Conclusions. The use of LT in patients has a dose-dependent positive effect on LVEF. The largest LVEF is observed in patients taking the drug at a dose of > 1.2 μg/kg. The use of an LT dose of > 0.53 μg/kg leads to a significant decrease in the frequency of re-hospitalization due to decompensation of heart failure during 2 years. Keywords: heart failure, autoimmune thyroiditis, levothyroxine, left ventricular, ejection fraction.

FIBROSIS: POLYETIOLOGIC COMPLICATION WITH COMMON DENOMINATOR

State of the problem. The growth of fibrous connective tissue is a common complication of various pathological processes, which significantly complicates recovery and is one of the leading causes of death. Despite many years of research, the process of fibrosis development remains insufficiently studied and contains a large number of “white spots”. Fibrosis is characterized by unpredictability, propensity to grow and low level of the replacement by normal connective tissue. The structure of fibrous tissue, its differences from normal and the reasons for the formation of these differences deserve no less attention. The formation of fibrous tissue is preceded by the process of endogenous intoxication – the formation and accumulation of various abnormal metabolites. Among the latter, the leading place belongs to proteins and peptides, whose structure is disrupted and destabilized. It is known that destabilized proteins are prone to aggregation. This process, contrary to popular belief, is not chaotic, but is subject to certain laws and is aimed at minimizing of free energy. With regard of the latter circumstance a definite favorite is the formation of β-structured fibrils, which occupy almost the lowest energy level among protein conformational states. Such fibrils are characterized by insolubility, resistance to proteolysis, immunogenicity and the ability to autochthonous growth due to sorption and conformational rearrangement of soluble proteins. A classic example of such aggregation is amyloid formation, but there are good reasons to assume similar processes in the formation of other pathological tissues. The aim of the work was to verify experimentally the presence of β-structured protein aggregates in fibrous tissues, which differ in etiology. The methodical part included the selection of surgical material, its fixation in 10 % formaldehyde solution, preparation of Congo-stained red histological specimens and microscopic examination in light, polarization and fluorescence modes. Results. The presence of β-structured protein aggregates in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of drugs has been proven experimentally. The identified phenomenon allows us to approach the understanding of the mechanisms of fibrosis development and to postulate a key role of regular aggregation of destabilized proteins. Conclusions. The obtained data testifies to a general and integral participation of β-structured protein aggregates in the formation of fibrous tissues of different etiologies. The presence of these deposits in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of the cytostatic doxorubicin has been shown. The leading role of violation of protein homeostasis and local accumulation of structurally damaged proteins as a prerequisite for autochthonous aggregation process is discussed. The expediency of fluorescence microscopy has been shown, which significantly expands the possibilities of detecting with the help of the Congo red of nanosized β-structured protein aggregates, which are invisible due to Abbe's limitations in light and polarization microscopy. Key words: fibrosis, keloidosis, Peyronie’s disease, Covid-19, cytostatics, nanoparticles.

Pesticides as endocrine distruptors of the reproductive system (literature review and own research)

Currently, one of the main threats to human health is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of homeostasis maintenance, controlled by the endocrine system, the purpose of which is to maintain normal functions and development in a constantly changing environment. Pesticides can disrupt the physiological functioning of many endocrine axes, including the endocrine mechanisms that ensure reproductive health. It should be noted that research aimed at preventing chemically induced reproductive disorders in the human population is one of the central areas of preventive medicine, both in terms of their importance and the complexity of the tasks being solved. Analysis and generalization of the results of our own long-term studies have shown that the selective, and, therefore, the most dangerous toxicity of pesticides for the reproductive system is determined by endocrine-mediated mechanisms of etiopathogenesis. The low level of doses inducing pathological changes in reproductive function in our studies fully confirms one of the universal signs inherent in endocrine-distruptive compounds. The above examples demonstrate a wide range of possible endocrine-mediated mechanisms of reproductive toxicity of pesticides - endocrine disruptors. However, it is very important to note that low doses may be more effective in changing some endpoints compared to high (toxic) doses. Currently, several mechanisms have been identified and studied that demonstrate how hormones and ED induce non-monotonic reactions in animal cells, tissues and organs. The reproductive system, the functioning of which is ensured by a fine balancing of the action of androgens and estrogens, is one of the systems that presents a unique opportunity for modeling a non-monotonic dose dependence. All of the above indicates the extreme danger of the impact of hormonally active agents on the reproductive health of a person and his offspring. At the same time, the threat of endocrine-mediated disorders for subsequent generations can also be realized through the induction of mechanisms of development of epigenetic transgenerational effects. Taking into account the results of studies of the mechanisms of the ED destructive action, as well as their ability to induce non-monotonic dose dependence at an extremely low dose level, it should be admitted that, apparently, there is a need to revise the paradigm of methodological approaches to the regulation of pesticides with endocrine-disruptive properties. Key words: pesticides, endocrine disruptors, reproductive system

INFLUENCE OF ATP-LONG AND MOLSIDOMINE COMBINATION ON THE BIOELECTRIC ACTIVITY OF THE MYOCARDIAL OF YOUNG AND OLD RATS IN CHRONIC SOFT STRESS

Introduction. Age-related changes in the cardiovascular system lead to a decrease in its reserve adaptive capabilities and an increase in the likelihood of developing diseases under stress and overstrain. A number of experiments have proven the significant role of emotional overstrain and stress in the development of cardiovascular diseases. The high incidence of the circulatory system, the long course and severity of diseases in elderly and old people determine the relevance of the search for treatment using effective and safe drugs. Aim: iinvestigate the effect of a combination of ATP-LONG and molsidomine on the functional state of the myocardium of young and old rats under chronic soft stress. Materials and methods. In experiments on young (10 months) and old (24 months) male Wistar rats, the cardiotropic and cardioprotective activity of the combination of the metabolic cardioprotector ATP-LONG and the vasodilator molsidomine was studied under conditions of chronic soft stress. Results. The negative impact of chronic soft stress on the bioelectrical activity of the myocardium – a violation of the processes of repolarization, conduction and contractility of the heart was found in young rats. The combination of ATP-LONG and molsidomine normalized the bioelectrical activity of the myocardium and increased its resistance to stress factors. In old rats under the influence of chronic stress, signs of impaired repolarization and electrical instability of the heart were more significant than in young animals. The combination ATP-LONG and molsidomine prevented the damaging effect of chronic stress and contributed to the normalization of the electrophysiological parameters of the myocardium of old rats. Conclusions. The results of experiments indicate the pharmacological cardiotropic activity of the combination of ATPLONG and molsidomine in young and old rats with chronic soft stress. Keywords: young rats, old rats, chronic soft stress, myocardium, electrocardiogram, bioelectrical activity of the heart, ATP-LONG, molsidomine, cardioprotective effect.

EVALUATION OF THE TUMOR PROLIFERATIVE ACTIVITY INDEX PCNA IN A VARIETY OF ROUTES OF DELIVERY OF CHEMOTHERAPEUTIC DRUGS IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER

Introduction. Breast cancer is one of the most live issue of the modern oncology, as it holds the leading position among the causes of female mortality and disability. A special place in the structure of this pathology is occupied by locally advanced forms of malignant tumor in which the effectiveness of the treatments used is unfortunately very low, therefore the prognosis is rather unfavorable. This determines there levance of them search for new methods of diagnosis and treatment in such patients. In the context of this research, we identified the role of neoadjuvant selective intra-arterial polychemotherapy in adverse primary inoperable forms of breast cancer. To determine and predict the effectiveness of this treatment, we used tumor proliferative activity. The research examined the expression of a PCNA nuclear proliferation marker for prognostic and diagnostic evaluation in the light of unsatisfactory literature on the subject in the context of determining similar parameters by other criteria. PCNA level was taken as the main dichotomous point of prognostic assessment of neoadjuvant therapy based on the results of retrospective analysis of the efficacy of preoperative treatment and determination of statistically significant difference between the results in the subgroups with lower and higher marker levels, which in our study were divided according to the median value of the immunohistochemical parameter level in the total sample of 25 %. Objective. Evaluation of the effectiveness of neoadjuvant treatment using systemic and selective intraarterial routes of chemotherapy administration in patients with locally advanced breast cancer using the tumor proliferative index based on the PCNA marker. Materials and methods. A retrospective analysis of the results of a comprehensive treatment of patients with initially inoperable locally advanced breast cancer based on selective and systemic routes of administration of chemotherapy was performed. The study included 63 patients. The sample was divided into 2groups depending on the selected type of neoadjuvant polychemotherapy: 1st group – control group were formed (based on systemic therapy) and 2nd group – study group (the selective intraarterial delivery route was used). The control group consisted of 22 patients, the study – 41 patients. All patients revealed stage IIIb of the disease. In accordance with the clinical manifestations, the patients were distributed as follows: control group include 12 patients with сT4bN1M0, 6 patients with сT4aN1M0 and 4 patients with сT4cN1M0; study group include 23 patients with сT4bN1M0, 7 patients with сT4aN1M0 and 11 patients with сT4cN1M0. All patients included in the study had luminal type B. In parallel with routine methods, the dynamics of proliferative activity of the tumor by the PCNA nuclear antigen was additionally studied in all patients. This study demonstrates the level of the PCNA marker at the start of treatment and after the completion of polychemotherapy (PCT). After PCT, all patients underwent surgical intervention. Taking into account the pathological examination, the patients were reassigned as follows: in the control group, 4 patients has pT4aN0M0, 2 patients – pT4aN1M0, 4 patients – pT4bN0M0, 8 patients – pT4bN1M0, 1 patient – pT4cN0M0 and 3 patients – pT4cN1M0; in the study group, 3 patients has PT4aN1M0, 4 patients – PT4aN0M0, 15 patients – PT4bN1M0, 8 patients – PT4bN0M0, 6 patients – PT4cN1M0 and 5 patients – PT4cN0M0. Since the patients belonged to the group with Luminal type of tumor, each of them received hormone therapy in an adjuvant regimen. Patients of reproductive age were treated with the group of estrogen antagonists, while postmenopausal patients received aromatase inhibitors. Targeted therapy was not used in the study. A statistical analysis was performed between the comparison groups; the median marker level in 25 % was taken as the critical value. Results. According to the degree of PCNA regression, it was determined that selective intra-arterial chemotherapy for breast cancer with a low proliferative activity index has a statistical advantage in overall survival and average life expectancy (p < 0.05) compared with control group. Conclusions. Using the PCNA indicator, one can reliably evaluate the proliferative activity of the tumor, thus predicting the effect of neoadjuvant chemotherapy and choosing the optimal tactics of complex treatment. Keywords: locally advanced breast cancer, proliferative activity index, marker of nuclear antigen of proliferating cells, systemic polychemotherapy, selective intra-arterial polychemotherapy.

THE ROLE OF THE INFECTIOUS FACTOR IN THE DEVELOPMENT OF CHOLANGITIS

Introduction. The problems of the pathogenesis of cholangitis have not been finally clarified to date. Aim: to investigate the dynamics of microbial contamination of the biliary tract in obstructive jaundice before and after decompression. Materials and methods. To determine the significance of the infectious factor in the development of acute cholangitis, bile from the common bile duct was examined in 40 patients with the biliary tract obstruction, which were divided into three groups according to the clinical course of the disease. Results. The quantitative infection indicators of the common bile duct were studied in asymptomatic choledocholithiasis, in obstructive jaundice without clinical manifestations of cholangitis and in a developed clinic of cholangitis. It has been proven that endoscopic decompression of the biliary tree allows to obtain an almost instant therapeutic effect, the number of colony-forming units of the pathogen decreases by almost three orders of magnitude within 3 days. However, in phlegmonous inflammation of the bile duct wall patients, this period was significantly lengthened, and the course of the disease, according to the Tokyo Guidelines (2013), was assessed as severe. Conclusion. In the study of quantitative infection indicators in patients with a bright clinic of cholangitis, a significant decrease in the number of colony-forming units was observed already on the third day after endoscopic papilosphincterotomy due to an adequate drainage effect. When a stone is driven into the large papilla of the duodenum, the common bile duct turns into an analogue of an abscess. Opening the papilla not only frees the mouth of the duct from the stone, but also provides free passage of the contents of the common bile duct (pus) into the duodenum. This provides an almost instant healing effect. When comparing the severity of cholangitis with the histological picture of the wall of the bile ducts (common bile duct, intrahepatic ducts), data were obtained that it is in patients with a severe form of the disease that phlegmonous inflammation of the wall of the duct system takes place. When comparing the severity of cholangitis with the histological picture of the wall of the bile ducts (common bile duct, intrahepatic ducts), data were obtained that phlegmonous inflammation of the wall of the duct system is observed precisely in patients with a severe form of the disease. Keywords: cholangitis, endoscopic decompression

CHANGES IN LIPID PEROXIDATION IN THE REPRODUCTIVE ORGANS OF MALE RATS DUE TO THE TRANSPLACENTAL ACTION OF CHEMICAL ENDOCRINE DISRUPTORS

In everyday life, people come into contact with chemical products that have hormone-like properties, for example, antiandrogenic (dibutyl phthalate, DBP) or estrogenic (bisphenol A, BPA). For a number of years, the issue of the potential harm of low doses of these endocrine disruptors (ED) for a developing fetus after entering the body of a pregnant mother has been discussed. Taking into consideration the ED ability to overcome the placental barrier, and the fact that one of the general mechanisms of the pathogenic effect of ED on humans and animals is oxidative stress, it is reasonable to study the state of lipid peroxidation (LPO) in the reproductive organs of adult male offspring, which was subjected to prenatal effects of low doses of DBP and BPA. The aim is to elucidate the prenatal effect of low doses of DBP and BPA on the content of LPO products in the ventral prostate (VP) and gonads of adult male rats. Material and methods. Wistar rats received orally an oil solution of DBP at 100 mg / kg bw. or BPA in Dorfman gel at 25 μg / kg bw per day from 15 to 21 days of pregnancy, control animals – carriers of drugs. In male offspring of 6 and 18 months of age, the contents of LPO products – malonic dialdehyde (MDA) and diene conjugates (DC) – were determined per mg of protein in the VP and testes. Results. In the testes of young rats prenatally exposed to DBP, the contents of both studied LPO products were significantly increased. The content of MDA in the VP of aging experimental rats exceeded 6 times, and DC – 1.5 times the values of control animals. The expression levels of MDA and DC in the testes of experimental animals increased by 134 % and 37 %, respectively. In the testes of 6-month-old rats exposed to BPA in utero, the contents of LPO products significantly increased in comparison with the control group: MDA by 155 %, DC – by 16 %. In the VP, the content of MDA significantly increased, DC did not differ from the control group. Conclusions. The result of oral administration of DBP to rats at a threshold dose relative to reproductive fetotoxicity during the last week of pregnancy is the activation of LPO in the testes of young and in the VP and testes of aging offspring. Oral administration of a subthreshold BPA dose to rats in the last week of pregnancy leads to the activation of LPO in the testes and the VP of young offspring. Key words: dibutyl phthalate, bisphenol A, prenatal action, lipid peroxidation, male rats, ventral prostate, testes.

MANAGEMENT OF PATIENTS WITH HEART FAILURE AND COVID-19

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Coronavirus 2 (SARS-CoV-2) severe acute respiratory syndrome. The virus was discovered in December 2019 in Wuhan, China. The advent of COVID-19 has posed challenges for healthcare professionals to quickly diagnose and provide medical care to patients. Currently, there is an intensive study of the clinical and epidemiological features of the disease, the development of new means of its prevention and treatment. The most common clinical manifestation of a new variant of coronavirus infection is bilateral pneumonia; in 3–4 % of patients the development of acute respiratory distress syndrome was recorded. In some patients, hypercoagulable syndrome with thrombosis and thromboembolism develops, other organs and systems (central nervous system, myocardium, kidneys, liver, gastrointestinal tract, endocrine and immune systems) are also affected, and sepsis and septic shock may develop. A high prevalence of concomitant diseases of the cardiovascular system has been shown, as well as their significant impact on the course of COVID-19 in such patients. Patients with pre-established medical conditions such as heart failure are at particularly high risk of morbidity and mortality from COVID-19. The risk of complications may be higher in patients with heart failure, not only because they are older and have more comorbidities, but also because of the specific characteristics of the syndrome. A correct understanding of the interaction between heart failure drugs and proposed drugs for the treatment of COVID-19 can help in the management of this category of patients. The article presents the main mechanisms of the influence of COVID-19 infection on the development of heart failure, the features of the course of this disease against the background of COVID-19. The authors describe the key methods of examining patients with heart failure with suspected COVID-19 disease, the features of the use of the main groups of drugs recommended for patients with heart failure, as well as moments of interaction between pharmacological drugs and the development of adverse side effects. Keywords: heart failure, COVID-19, SARS-CoV-2, comorbidity, pharmacotherapy.