Lviv Clinical Bulletin

8-14

Authors: KIovalyova O., Ashcheulova T., Kysylenko K.

Introduction. Hypertension is the most common chronic disease that has up to 20.0-30.0 % of the adult population of the planet. The presence of concomitant diseases, including obesity worsens the course and prognosis of Hypertension. Therefore, one of the pressing and studying problems at this time in the whole World is obesity and diseases associated with it. Along with obesity, an important factor in the risk of cardiovascular events, is a lipid metabolism disorder. In recent years, the concept has been formulated, according to which in the pathogenesis of lipid metabolism disoder an important role is played by the inflammatory process, mediated by cytokines. Interleukin-22, as shown by the results of previous studies, has a direct positive relationship with many cardiometabolic risk factors, including sex, smoking, and body mass index. However, the issue of interleukin-22 implication in the pathogenesis of obesity, dyslipidemia, especially in relation to exogenous postprandial hyperlipemia, is not sufficiently studied on the clinical level in hypertensive patients whis obesity. Aim. The study is devoted to determining the parameters of the lipid metabolism and the serum level of interleukin-22, as well as the relationship between them, in patients with hypertension, depending on the presence of excess body weight or concomitant obesity. Materials and methods. 80 patients with hypertension were examined. All patients were divided into three groups: group 1 (n = 19; 23.8 %) – patients with hypertension whis normal body weight, group 2 (n = 30; 37.5 %) – hypertensive patients with excess body weight, group 3 (n = 31; 38.8 %) – hypertensive patients with obesity. The control group included 12 healthy individuals. Levels of serum interleukin-22 were studied by using set Bender Medsystems® Human IL-22 Platinum ELISA. Results. According to the results of the study, in patients with hypertension of the third group there is a maximum content of total cholesterol, triglycerides, low-density lipoprotein cholesterol, very low density lipoprotein cholesterol, atherogenic index, remnant cholesterol and apolipoprotein B. The minimum content of high-density lipoprotein cholesterol is observed in the second and third groups of patients with hypertension. When comparing the parameters of lipid metabolism in the main groups of patients with hypertension and the control group, a significant increase in all atherogenic parameters in the main groups was revealed (p < 0.001). These data suggest that dyslipidemia is directly or indirectly involved in the mechanism of increasing blood pressure and the development of hypertension. Thus, hypercholesterolemia and dyslipidemia can directly affect the tone of peripheral vessels and, accordingly, on indicators of arterial pressure. It was noted that in hypertensive patients with excessive body weight and obesity revealed basal hypercholesterolemia, hypertriglyceridemia, hypoalphacholesterolemia, increased cholesterol levels of low density lipoprotein and cholesterol of very low density lipoprotein, and also the disturbance of lipid metabolism tolerance in the postprandial period, which is manifested by an increase the content of total cholesterol, triglycerides, cholesterol of low density lipoprotein, cholesterol of lipoproteins is very low density and decrease cholesterol of high density lipoprotein. More significant positive correlations of interleukin-22 with lipid metabolism parameters (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high density lipoprotein cholesterol, remnant cholesterol and atherogenic index) in patients with hypertension with concomitant obesity were found compared with a group of hypertensive patients without no signs of excessive body weight or obesity. Conclusions. Thus, the data obtained may indicate an interleukin-22 hypertensive effect. And the presence of close correlation relations of the investigated cytokine with parameters of the lipid spectrum may indicate that it is involved in increasing the severity of lipid metabolism disorders.

25-29

Authors: Skrypnyk I., Maslova G., Shcherbak O.

Introduction. An excessive activation of lipid peroxidation (LP) plays a significant role in pathogenesis of either ischemic heart disease (IHD) or nonalcoholic steatohepatitis (NASH) that in chronic conditions leads to depletion of antioxidant protection (AOP) enzymes with increased risk of cell damage resulted from the influence of aggressive free radicals. Aim. To investigate the dynamics of lipid peroxidation and antioxidant protection activity in patients with ischemic heart disease and comorbid nonalcoholic steatohepatitis under the pathogenetic treatment. Materials and methods. 59 patients with IHD associated with NASH were examined, 11 (18.6 %) of them were women and 48 (81.4 %) – men. An average age was 53.7 ± 8.5 years. An efficiency of treatment was assessed in 1-month and 6-month periods. Activity of alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (AP), gamma-glutamyltranspeptidase (GGTP) and total bilirubin content were analyzed in blood serum. Serum thiobarbituric acid-active (TBA-active) products, activity of superoxidedysmutase (SOD) were evaluated. Depending on prescribed therapeutic scheme patients were divided on groups: І (n = 31) – rosuvastatin 20.0 mg per day, ursodeoxycholic acid (UDCA) 15.0 mg/kg/day for 6 months, and L-carnitine 1.0 g bid for 3 months; ІІ (n = 28) – rosuvastatin 20.0 mg per day and UDCA 15.0 mg/kg/day, 6 months. Results. 1 month after the treatment with rosuvastatin 20.0 mg per day in combination with UDCA and L-carnitine in patients of the group І ALT activity decreased 1.8 fold, AST – 2 fold, GGTP – 2.8 fold in comparison with the indexes before the treatment. Among the patients of the group ІІ, who received treatment with rosuvastatin 20.0 mg per day in combination with UDCA, serum ALT decreased 1.5 fold, GGTP – 1.8 fold. In 6-month period serum ALT activity decreased 2.3 fold, AST – 2.4 fold, GGTP – 2.9 fold in patients of the group І in comparison with the indexes before the treatment. GGTP, AP and bilirubin levels were normal. In patients of the group ІІ ALT activity decreased 1.7 fold, AST – 2 fold, GGTP – 2.2 fold in comparison with the indexes before the treatment. In patients of the group I in 1-month and 6-month periods of treatment serum TBA-reactants decreased 1.9 fold and 2.8 fold respectively with simultaneous SOD activity rise 1.9 and 2.2 fold respectively in comparison with primary evaluation. In patients of the group II in 1-month treatment period content of TBA-reactants decreased 1.7 fold and in 6-month period – 2.9 fold in comparison with the indexes before the treatment. Yet, SOD activity increased 1.9 fold only in 6 months after the treatment. Conclusion. Combination of ischemic heart disease and nonalcoholic steatohepatitis is accompanied by thiobarbituric acid reactants 3-fold increase and superoxide dismutase 2.3-fold decrease in blood serum in comparison with norms on the background of elevated transaminases. Additional prescription of ursodexoycholic acid and L-carnitine combination for 6 months on the background of pathogenetic therapy allows to decrease thiobarbituric acid reactants 2.8 fold and to increase superoxide dismutase – 2.2 fold.

35-39

Authors: Katerenchuk O., Zhdan V., Katerenchuk I.

Introduction. Coronary arteries disease or, as it still often named, ischemic heart disease is responsible as for premature death in acute conditions (occurrence of acute coronary syndromes) as for premature death caused by progression of chronic heart failure (CHF) of ischemic etiology. The pathophysiological mechanisms that lead to the occurrence and progression of psychosomatic and autonomic disorders (in particular, depression) in patients with CHF coincide with the mechanisms of progression of the syndrome of CHF per se. The solution of this problem lays in adequate primary and secondary prophylaxis of heart function deterioration in patients with coronary arteries disease by taking into account psycho-autonomic disturbances that should be used as markers of increased risk for heart failure decompensation. Aim. To evaluate diagnostic and predictive value of psycho-autonomic dysfunction as factor of CHF progression in patients with coronary arteries disease. Materials and methods. The state of autonomic tonic activity was evaluated by analyzing heart rate variability using the diagnostic complex Fasagraf. Psychosomatic misbalance was estimated by filling the Hospital Anxiety and Depression Scale. The calculation of relative risk was carried out by constructing four-squared tables. Results. The study included 151 patients, divided into 4 groups, depending on the presence of isolated or combined vegetative and psychosomatic disorders. In 3 and 6-month periods, the occurrence of signs of decompensation of heart failure was assessed. The presence of a combined psycho-autonomic imbalance was characterized by a statistically significant increase in relative risk for occurrence of all signs of CHF progression (exception only for hospitalizations) compared with the control group in 3-months period of observation. The presence of isolated tonic hypersympathetic exertion resulted in elevated relative risk of edema progression, increasing in body weight due to congestion, for dyspnea progression and NYA class worsening. The presence of isolated psychosomatic imbalances led to a statistically significantly greater relative risk for the progression of edema and the stage of CHF and for progression of shortness of breathing with an increase in CHF NYHA class. The presence of combined psycho-autonomic misbalance during the 6-month period of observation resulted in statistically significant increased relative risk for all parameters of CHF progression, even with the slight increase of it compared to the relative risk in the 3-months period. In a group with solid psychosomatic disorders, the relative risk did not have statistically significant differences compared to the control group. In the group of patients with solid tonic sympathetic exertion tone the relative risk was higher for progression of shortness of breath and CHF NYHA class, edema and CHF stage worsening and for the increasing needs for more aggressive therapeutic tactic. Conclusions. The presence of combined psycho-autonomic disorders or tonic isolated hypersympathetic state causes an increased risk of CHF progression in 3- and 6-months periods. The presence of isolated psychosomatic disorders is characterized by a decrease in the relative risk of progression of dyspnea, edematous syndrome, NYHA functional class and the stage of heart failure during 6-months follow-up period due to regular aerobic exercises and optimal pharmacological treatment.

54-59

Authors: Мarkin L., Besedin О., Іsayeva K.

Introdaction. Nowadays, the combination of pregnancy and uterine leiomyoma has been increased by 20 %. The presence of uterine leiomyoma is associated with a high risk of obstetric and perinatal complications. A lot of studies are dedicated to the search for modern treatment methods. But many issues remain unsolved and controversial, especially regarding surgical treatment of pregnant women with leiomyoma. Aim. To improve methods of conservative and surgical treatment of pregnant women with uterine leiomyoma in the complicated course of pregnancy due to accomplish maternal and perinatal consequences. Materials and methods. 47 pregnant women with uterine leiomyoma underwent inpatient treatment due to complicated course of pregnancy and were under observation. Surgery was conducted in 20 (42.6 %) among these patients. The analysis of complaints, anamnestic data, peculiarities of the course of pregnancy and its complications, indications for operation, the course of operation and postoperative period, pathological and anatomical conclusions, the condition of intrauterine fetus and a newborn was conducted to solve tasks. Results. Previous violation of reproductive function was observed in 78.7 % of pregnant women. The term of pregnancy was in the range from 7 to 36 weeks. All examined women had various pregnancy complications. Threatened miscarriage and threatened preterm labor were in 93.6 % of cases, late gestosis – in 59.6 %, FGRS – in 21.3 %, malposition, malpresentation – in 14.8 %, anemia of pregnant women – in 23.4 % of cases. Complications regarded to leiomyomatous nodes were marked in 32 (68.1 %) of pregnant women, corresponding to the diagnosis of complicated uterine leiomyoma. Prognostically unfavorable course of pregnancy was on the background of large and huge leiomyomatous nodes, multiple uterine leiomyoma particularly with interstitial and subserous interstitial localization. Pregnancy had been prolonged using pathogenetically-based schemes of treatment and surgical treatment in 45 of pregnant women with uterine leiomyoma and complicated course of pregnancy; subsequent parturition through natural birth happened in 12 (25.5 %) of cases and Caesarean section was conducted in 28 (59.5 %) of cases. Another 5 pregnant women are under observation. Pregnancies have been completed by the birth of living newborns in 40 (95.2 %) of cases. Conclusions. Apparently, the relevant operating techniques, tactics, post-operative care, preventive and therapeutic measures allow avoiding many intra- and postoperative complications. Leiomyomectomy should be a choice option for pregnant women, which allows prolonging pregnancy and maintaining the reproductive function. This problem remains relevant and requires further randomized controlled trials to provide the most reliable data and to create regulatory framework with the aim to optimize tactics of conducting pregnant women with this pathology despite significant progress in improving diagnostic and treatment methods of uterine leiomyoma.

8-13

Authors: Emelyanova N.

Introduction. The priority of modern dentistry is a constant research of pathological changes in oral cavity occurring in patients with (COPD). Today under COPD we understand the growing abuse of lung function that caused lung tissue inflammatory response to stimulation by various agents. We know that more than 55.0 % of COPD cases are comorbid with coronary heart disease (CHD). COPD and CHD are accompanied by the emergence of systemic hypoxia, which in addition to the existing metabolic disorders of oxygen deficiency in periodontal tissues depresses regeneration and reparative processes. Results of clinical studies suggest that fairly simple methods of non-invasive exfoliative cytology allow us to determine the impact of various systems and external factors on the parameters of cells and cellular structures in the presence of various states of gums pathology. Both diseases have direct effect on periodontal tissue manifesting in cell anomalies such as micronucleus, binuklear cells, karioreksis, kariolisis, protrusion, vacuolization, and halo (coylocytosis). Aim. To find out the frequency and nature of epithelial cell nucleus in patients with COPD comorbid with CHD. Materials and methods. We examined 239 patients aged 45 to 65 years (157 men and 82 women) with verified diagnosis of COPD and CHD. They were divided into groups depending on the underlying disease: the main group – 130 patients with COPD comorbid with CHD, comparison group N 1 – 38 patients with COPD, and comparison group N 2 – 71 patients diagnosed with CHD. Cytology was performed on the gingival epithelium scrapes using light microscope. Also we used digital videocamera CAM 2800 with light microscopy to take photos of cells. Abnormal cells rate was determined in 1/1000 terms. Statistical analysis was performed with “SPSS 13” computer. Results. All patients with somatic disorders have significant morphological changes of epithelial cells, increased number of non-nuclear cells, and cells with large nuclei evenly colored. At the same time the nucleus of epithelial cells from healthy donors were small and compact. Patients of the main group showed the highest level with micronuclei cells determined pathological processes and violation of apoptosis. In addition, patients of the main group and the comparison group number 1 had more than 2 times higher rate of binuclear cells in comparison with the control group, and also with group of patients with coronary artery disease. The highest rate of core protrusions was also inherent in the study group, whish frequency in patients with COPD increased significantly and exceeded targets by more than 9 times. COPD and CHD may contribute to the presence of hypoxia, microcirculatory disorders and vascular permeability, increased lipid peroxidation. Most likely is the probability of rise above violations and growth in the epithelium of patients with increased number of cells vacuolization, which is a sign of an early destruction of cells, including destructive changes of cell membranes, reducing their barrier and transport functions. Conclusions. Results of the study indicate that the most significant changes of cells nucleus were found in patients with comorbid broncho-cardiac pathology and display stereotypical features of chronic inflammation. Thus, we can draw a conclusion about genotoxic impact of physical illness or its treatment of the manifestations of epithelial cell abnormalities on the patients with COPD comorbid with coronary artery disease.

21-24

Authors: Shulaia T., Kiladze N., Bulinska A., Abrahamovych L.

Introduction. Acral nevus is a benign melanocytic proliferation at the palms and soles, which occurs in approximately 4.0 % of people with white skin. Sometimes the differentiation of acral nevi and acral lentigious melanoma can be difficult, and in these cases the correct interpretation of dermatoscopic picture can be crucial. Aim. To investigate the dermoscopic features of 306 acral melanocytic nevi, to determine the most common patterns and to trace their connection with development of acral lentiginous melanoma. Materials and methods. The article presents the results of a dermatoscopy examination of 306 acral melanocytic nevi in 117 Caucasian patients with I-II skin type. For each patient was collected data of the predominant body pattern of the nevi, the number of volar lesions, the location and diameter of each volar lesion and dermoscopic patterns. Lesions located on dorsal areas were excluded. Digital dermoscopic images were captured with a Sumsung Galaxy S4 digital camera equipped with a Dermlite DL3 dermoscope. Results. In 84.0 % of cases the typical dermatoscopic pattern for acral nevi were parallel lines located in the furrows. In 14.0 % parallel lines in the furrows were connected with сrossing lines, giving the impression of reticular. As a rule, in each furrow was one pigmented line, in some cases there were two, but usually these lines were composed from dots and they were not continual. Among other elements dots, clods and structureless area were seen frequently, reticular lines less often, radial lines rarely. Among observed in 5 patients were detected 5 acral melanomas. Each nosological unit of acral lesion has its particular dermatoscopic pattern that helps to differentiate between malignant and benign proliferation. Specific dermatoscopic pattern of acral melanoma are structures of parallel line on the ridges, while for nevi typical patter are parallel lines in the furrows. Conclusions. The widespread introduction of dermoscopy into clinical practice will enable dermatologists to diagnose melanoma in its early stages and to avoid unjustified removal of benign tumors.

32-38

Authors: Serhiyenko V., Serhiyenko О.

Introduction. Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM), that is strongly associated with increased risk of cardiovascular mortality. CAN among type 2 DM (T2DM) patients, is characterized by lesion of nerve fibers in the sympathetic and parasympathetic divisions of the autonomic nervous system, is diagnosed unsatisfactorily and may be accompanied by severe postural hypotension, decreased tolerance to the physical loadings, and cause the cardiac arrhythmias, ischemia of coronary vessels, ″silent″ myocardial infarction (MI), sudden death syndrome. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heard rate to development of ″silent″ MI. Although it is a common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. The pathogenetic treatment of CAN include lifestyle modification, intensive glycemic control, treatment of dyslipoproteinemia (DLP), correction of metabolic abnormalities in the myocardium, thrombosis prevention, prescription of α-lipoic acid, aldose reductase inhibitors; γ-linoleic acid, acetyl-L-carnitine, antioxidants, long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), vasodilators, vitamin B1 and some other substances. American Diabetes Association (2016) recommend the prescription of ω-3 PUFAs in algorithms of DLP treatment among patients with T2DM and cardiovascular diseases. However, the data about the ω-3 PUFAs effectiveness are incomplete, the future investigation are needed. The aim of the study was to investigate the content of some pro- and anti-inflammatory factors, insulin resistance parameters in patients with T2DM and CAN, influence of ω-3 PUFAs on these parameters. Materials and methods. The study involved 48 patients with T2DM (16 women, 32 men, patients were aged between 50-59 years), among them: 1) 12 patients with T2DM without CAN; 2) 36 (aged 50-59 years, disease duration 1-6 years, glycated haemoglobin (HbA1c) level (7,1 ± 0,6) %) – with functional CAN stage. Control group – 15 healthy people of median age (51,9 ± 3,2) years. The concentration of glucose, immunoreactive insulin (IRI), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8 and IL-10 in the blood were determinate; insulin resistance index (HOMA-IR) and TNF-α/IL-10 ratio were calculated. Patients with T2DM and functional stage of CAN were divided into 2 groups: patients of 1nd group (n = 21) received one capsule/day of the ω-3 PUFAs in addition to standard treatment, each one gram capsule of the ω-3 PUFA contains approximately 465 mg of eicosapentaenoic and 375 mg of docosahexaenoic acid and 4,0 g of tocopferol acetate; patients of 2nd group (n = 15) received standard glucose lowering therapy (control group). The duration of the study was 3 months. Results. According to the results of our study there can be seen the increase of IRI, HOMA-IR levels are accom- panied with increase of hsCRP, TNF-α, IL-6, IL-8 and IL-10 (compared to the control). The development of func- tional stage of CAN was accompanied with statistically significant increase of IRI, hsCRP, TNF-α, IL-6, IL-8, IL-10 and TNF-α/IL-10 levels (compared to patients with T2DM without CAN). Obtained results could witness about the violation of cytokines dysbalance, development of compensative type of cytokine dysbalance. The administration of ω-3 PUFAs to patients with T2DM and CAN promoted to the statistically significant decrease in hsCRP, TNF-α, IL-6 and IL-8 levels and TNF-α/IL-10 ratio; but no statistically significant changes of IL-10, HbA1c, IRI and HOMA-IR was found. Conclusions. Obtained results could witness, that prescription of ω-3 polyunsaturated fatty acids leads to decrease of the proinflammatory immune response activity and allows to consider ω-3 polyunsaturated fatty acids as a promising medicine in the treatment of cardiac autonomic neuropathy in patients with type 2 diabetes mellitus.

44-47

Authors: Mashkarynets O.

Introduction. More than 60.0 % of girls of pubertal period of growth suffered from different disturbances of menstrual functions. It is known that pathological processes in periodontal tissues are diagnosed more often among girls with disturbances of menstrual function comparing to the girls of the same age with regular menstrual cycle. Aim. To investigate the frequency and clinical appearance of the chronic catarrhal gingivitis in girls with disturbances of menstrual cycle and healthy girls. Materials and methods. There were examined 91 girls of 15-16 years in order to study the frequency of periodontal tissues diseases. Examined girls were on the dispansary account in teenager gynecology rooms of Lviv Municipal Polyclinic N 4, 5, 6 and on the treatment in the teenager gynecology department of Lviv Regional Pediatric Specialized Clinical Hospital. Control group consisted of 112 healthy girls of the same age from schools N 1, 7, 19, 91, 21 from Lviv. Diagnostics of periodontal tissues diseases was carried out according to M. F. Danylevskiy’s classi- fication. The colour, relief, the state of the gindival papillae, presence of local irritating factors was determined during oral cavity examination. Pathological changes in periodontal tissues, the stage of process severity were estimated with the help of the following indicis:papillar-marginal-alveolar index; index of bleeding; index of S. P. Ramfjord; complex periodontal index; community periodontal index. Results. Pathological processes in periodontal tissues in girls with pathological course of menstrual cycle (MC) have been studied insufficiently. There were examined 91 girls of 15-16 years with MC disturbances and 112 healthy girls of the same age (control group). It was found that the prevalence of inflammatory periodontal diseases in the group of girls with pathological course of MC is significantly higher (87.85 ± 3.15 %), comparing to the control group (53.63 ± 3.36 %), (p < 0.001). Catarrhal gingivitis was diagnosed mostly among examined girls from both groups. The prevalence of catarrhal gingivitis in the group of girls with pathological course of MC is higher (79.40 ± 3.91 %) comparing to the same index of the girls from the control group (50.9 ± 3.37 %), (p ˂ 0.001). It was established that the chronic catarrhal gingivitis prevailed (88.63 ± 3.27 %) among all gingivitis. Hypertrophic gingivitis in girls with menstrual cycle disturbances was diagnosed in 2.79 ± 1.59 % persince and was abcesnt in healhy girls. The periodontitis frequency in girls with menstrual cycle disturbances and healhy girls is 5.64 ± 2.52 % and 2.71 ±1.10 %, accordingfly (р > 0.05). Clinical investigations with using of periodontal indices let us to reveal significantly higher indicis in girls with pathological course of MC comparing to the control group. Conclusions. The prevalence of periodontal tissue diseases in girls with a pathologic course of the menstrual cycle (87.85 ± 3.15 %) is significantly higher in comparison with the group of practically healthy girls (53.63 ± 3.36 %). Among gingivitis, the chronic catarrhal gingivitis predominates (88.63 ± 3.27 %). Also periodontal indices are significantly higher in girls with menstrual disorders, compared to practically healthy girls. The results can be used to determine the need of preventive care and treatment for the girls with menstrual disorders). Recived data is a base for determination of need of preventive help and treatment in girls with menstrual cycle disturbances.

53-72

Authors: Farmaha M., Abrahamovych M., Ferko M.

Introduction. Liver cirrhosis has a significant place among the diseases of internal organs and its comorbid syntropic lesions of the circulatory system are a common cause of disability, and often death of patients, determining the actuality, health, socio-economic importance and need for improvement of the principles of its integrated differential treatment, taking into account the state of the cardiovascular system. Aim. To analyze the studies on frequency, pathogenesis, clinics, diagnostics and treatment of polymorbid syntropic extrahepatic lesions of the cardiovascular system in patients with liver cirrhosis published until now. Materials and methods. We have worked on clinical research data for previous years and have analyzed a case of the disease of a particular patient who was under our observation. Results. Diseases of a liver as a key organ of the interorgan and intersystem relationships, lead to the circulatory system disorders. It appears, first of all, by the hemodynamics disorders with the formation of stable arterial hypotension and, consequently, microcirculatory disorders, functional failure of almost all organs and also myocardial damage resulting into cirrhotic cardiomiopathy with systolic and diastolic heart failure and changes of the heart’s parameters. The study of this problem started in Cappadocien Aretacus and Claudius Galenus, but there were only isolated reports. Detailed study of this problem began in the twentieth century. However, despite the lengthy study, today there is no there is no final answer to the questions of pathogenesis of the circulatory system lesions in patients with cirrhosis. At this moment, it is well known that cardiovascular homeostasis in patients with liver cirrhosis is associated with the presence and severity of portal hypertension and hepatocellular insufficiency, and among the molecular mechanisms the leading role is given to endothelial dysfunction with an imbalance in the system of vasoconstrictors (endothelin-1) and vasodilators (nitric oxide, carbon monoxide, hydrogen sulfide, prostacyclin, kanabioids, endogenous opioids and others), disorders in the renin-angiotensin-aldosterone system and in the autonomic nervous system. An imbalance in the mentioned system leads to the systemic vasodilation, which is the most pronounced in splanhnic vessels, causing arterial hypotension and subsequent changes in the bloodstream and in the end, leads to polyorganic failure. These vasoactive substances are able to make the cardiodepressive effect and potentially participate in the pathogenesis of cardiomyopathy in the cirrhotic patients. Clinical signs of liver cirrhosis with the involvement into the process organs of the cardiovascularsystem is poor and, most importantly, non-specific. Most often there are no complaints or regarded as a manifestation of liver disease and the results of physical, laboratory and instrumental examination are of low information. The most specific is a high heart rate, presence of «chronotropic insufficiency», the level and daily fluctuations of blood pressure. Specific treatment of the cardiovascular system lesions in case of liver cirrhosis have been not developed till now. Treatment of such patients should be individualized, aiming at the support of myocardial function and prevention of circulatory decompensation. Conclusions. According to a literature review the injury of a liver as a key organ of interorgan and intersystem relationships, leads to the disorders of the circulatory system and manifests with the hemodynamics violation resulting into the formation of stable arterial hypotension and myocardial damage known as cirrhotic cardiomiopathy with systolic and diastolic heart failure and changes of the parameters of the heart. However, disorders of blood flow in patients with liver cirrhosis require further elucidation of features of the pathogenetical mechanisms of its appearance, which will justify the new principles of the effective treatment of this category of critically ill patients.

7-11

Authors: M. A. Stanislavchuk, A. Al Salim

Objective. To establish the features of cardiac remodeling in patients with postinfarction cardiosclerosis and type 2 diabetes based on gene polymorphism leptin receptors LEPR Q223R. Materials and methods. The study involved 147 patients with stable coronary heart disease (CHD) with postinfarction cardiosclerosis (100.0 % of men aged 53.0 ± 7.83 years). Type 2 diabetes was detected in 64 (43.5 %) patients. CHD was established regarding the recommendations of the AHA/ACC (2014) and ESC (2013), verification of the diagnosis of type 2 diabetes was conducted under the existing criteria. Gene polymorphism LEPR Q223R determined by PCR mode Real­Time. Echocardiographic studies were performed in M­, B­ and D­mode on the ″Logic 500 Sono Series″ (General Electric, Korea). Results and discussion. In CHD patients with type 2 diabetes size of the left atrium was significantly higher than those in patients with CHD without diabetes. In men with postinfarction cardiosclerosis and type 2 diabetes was registered significantly higher myocardial mass, wall thickness, end systolic and diastolic dimensions than in patients without diabetes. In patients with CHD with type 2 diabetes final systolic size, end systolic volume, and end systolic extent index were significantly higher than in patients with CHD without diabetes. Presence of type 2 diabetes in patients with CHD was associated with the increase of end­diastolic volume, and left ventricular mass. In patients with postinfarction cardiosclerosis and type 2 diabetes was noted a significant worsening of cardiac systolic function: the degree of shortening of the anteroposterior size of the left ventricle (ΔS) in systole and ejection fraction were 7.4 and 6.6 % lower than in patients without diabetes. Among patients with CHD there were revealed 25.2 % homozygotes QQ, 42.4 % ­ QR ­ heterozygotes and 32.7 % ­ RR homozygotes. RR genotype was associated with a higher frequency of maladaptive remodeling type characterized by the dilation of the heart’s chambers and thinning of the myocardium walls, especially in patients with type 2 diabetes. The frequency of the eccentric hypertrophy in homozygotes RR was 77.0 % and was significantly higher than among carriers of allele Q (OR = 4.60, 95,0% CI 2.13­9.94), while the frequency of concentric left ventricular hypertrophy was significantly lower (2.3­2.5 times, p < 0.05). Based on the multiple linear regression analysis it was confirmed that the genotype RR gene LEPR Q223R is an independent predictor of decrease of ejection fraction in patients with CHD associated with Type 2 diabetes. Conclusions. Gene polymorphism of LEPR Q223R is a predictor of maladaptive type of cardiac remodeling in patients with postinfarction cardiosclerosis and type 2 diabetes.

16-25

Authors: M. Abrahamovych, O. Abrahamovych, S. Tolopko, M. Ferko

Introduction. Engaging of the different organs and systems into the pathological process, including the organs of the respiratory system, interpretated as syntropic co­ and polymorbid lesions, including the most common ­ hepatopulmonary syndrome (HPS), in many cases determines the severity of the general condition of the cirrhotic patients, leads to a significant reduction of their life quality, disability, has a decisive prognostic value at all the stages of the treatment and is the leading cause of the death of the hepatological patients. Taking into the account the poor prognosis and high mortality (41.0 %) of the patients with the HPS, it is required the constant monitoring and paying the special attention of the physicians to such patients and also prescribing the adequate pathogenesis­based drugs to optimize the treatment. The aim of our study was to modify the treatment of the cirrhotic patients with the hepatopulmonary syndrome of different severity degrees on the base of clarifying the characteristics of their pathogenesis and to evaluate its effectiveness. Materials and methods. Into the study in randomized manner with the preliminary stratification by the presence of the HPS were involved 93 patients [26 women (28.0 %) and 67 men (72.0 %); aged 27 to 67 years, who were treated in Lviv Regional Hepatological Center during 2012­2015. To elucidate the pathogenesis of the HPS for appointing the most effective pathogenetically reasonable treatment, we have determined the content of some vasoactive humoral and metabolic factors, namely the endothelium­dependent (cyclic guanosine monophosphate (cGMP), endothelin­1 (E­1)), tumor necrotizing factor α (TNF α) and the indices of the renin­aldosterone system (renin, aldosterone) in the blood plasma of the patients by ELISA. Also there were examined the gas composition of the venous blood and the acid­base balance (ABB) state. To determine the effect of the mediators of the autonomic nervous system (ANS) on the vascular tone, we have assessed its state by the registration of the heart rate variability (HRV). After the treatment clinically and laboratory indices and life quality of the patients of the experimental group (EG) who were treated by the modified by us technique and of the control group (CG), where the patients received the standard treatment were evaluated. Results. During the study of some pathogenetic mechanisms of the HPS it was found the inverse correlative connection between the values of carbon dioxide partial pressure, bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid and the severity of the HPS, which was manifested by the progressive metabolic acidosis that required the medical correction. With the growth of the severity of the respiratory lesions the levels of cGMP, E­1, TNF α, renin and aldosterone in the blood plasma of the cirrhotic patients were significantly (p < 0.05) increased, which made theim to be the criteria to justify the appointment of the pathogenetic treatment. During the diagnosis of the ANS state in the cirrhotic patients with the syntropic respiratory lesions using HRV registration we proved the overwhelming influence of the sympathetic part over the parasympathetic in the patients with the I degree HPS with the directly proportional increase of the neurohormonal effects according to its severity. The modified by us method of the treatment of the patients considering the investigated pathogenic mechanisms of the liver cirrhosis and the HPS, its severity, as well as the conventional one, gave the positive result, but by its quality parameters the conventional medical complex significantly yielded comparing to the modified by us algorithm. Statistical analysis of the questionnaires MOS SF­36 before and after the treatment indicated a significant (p < 0.05) improvement of the physical activity, vitality, mental and general health, reducing of the pain and the role of the emotional stress in disability, resulting into the improvement of the physical and mental status of the patients treated by the modified by us technique and shows its effectiveness. Conclusions. Investigations of the indices of ABB (carbon dioxide partial pressure, levels of bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid) the endothelium­dependent (cGMP, E­1), TNF α and the indices of the renin­aldosterone system (renin, aldosterone), the state of the ANS and their dependence on the severity of the HPS substantiated the advisability of including into the medical complex of the patients with the I degree HPS in addition to the detoxification, diuretic and hepatoprotective treatment the electrolyte combined isotonic solution (sodium, potassium, magnesium, calcium chloride, acetate, malate) ­ 500.0 ml intravenously once a day, pentoxifylline ­ 1 tablet (100.0 mg) twice daily, spironolactone ­ 1 tablet (25.0 mg) twice daily, carvedilol ­ 1 tablet (3,125 mg) once a day; with the II degree HPS ­ 4.0% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 100.0 ml intravenously once daily, valsartan ­ 1 tablet (40.0 mg) once daily, spironolactone ­ 1 caps. (50.0 mg) twice a day; with the III degree HPS ­ 4.2% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 200.0 ml intravenously once a day with the transition to oral use – 1 tablet (100.0 mg) of pentoxifylline twice daily, enalapril ­ 1 tablet (5.0 mg) once daily, spironolactone ­ 1 caps. (100.0 mg) twice a day. Using the modified pathogenetic reasonable treatment in the cirrhotic patients taking into account the severity of the HPS allowed us to increase its efficiency by 13.7 % and to improve the physical activity, vitality, mental and general health, reduce pain and the role of the emotional problems in disability, leading to the improvement of physical and mental status of the patients.

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Authors: U. Abrahamovych, O. Abrahamovych, L. Tsyhanyk, O. Synenkyi, S. Guta

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the chronic inflammation and multisystemic damages, accompanied by lesions in osteoarticular system, including secondary osteoporosis (OP) ­ an important risk factor for low­energy fractures. The most common noninvasive osteoporosis tests currently in use in Ukraine include ultrasound densitometry and X­ray densitometry (dual­energy X­ray absorptiometry (DXA) and hand bone X­ray densitometry). The objective is to compare diagnostic values of bone mineral density tests that employ ultrasound densitometry, X­ray osteodensitometry, and dual­energy X­ray absorptiometry in premenopausal women with SLE. Materials and methods. The study randomly included 51 women aged between 21 and 53 (mean age at the time of the study – 38.21 ± 1.66) which were diagnosed with SLE according to the criteria of the American College of Rheumatology (1982, 1997); all women at the time of the study were premenopausal. 100.0 % of the patients received methylprednisolone at a dose of 4.0 to 24.0 mg/day (average dose – 11.12 ± 0.81 mg/day) and calcium supplements at a dose of 1000.0 mg/day in combination with vitamin D at a daily dose of 400.0 IU. The average duration of treatment with glucocorticoids and calcium supplements corresponded to the average disease duration. Bone mineral density was assessed through calcaneus ultrasound bone densitometry performed with SONOST-2000 device (OsteoSys Co., Ltd, Seoul, Korea), hand bone X­ray densitometry performed with “ARM­Osteoloh” application, and dual­energy X­ray absorptiometry of lumbar spine and proximal femur performed with dual­energy X­ray absorptiometer (Stratos, France). Statistical analysis of the obtained results was carried out in MS Excel and IBM SPSS Statistics applications. Results and their discussion. The results of ultrasound densitometry among 51 patients with SLE were as follows: 13 (25.49 %) women were diagnosed with osteoporosis (average T­score ­(­2.77) ± 0.08); 26 (50.98 %) women were diagnosed with osteopenia (average T­score ­ (­1.81) ± 0.08), 6 of them (11.76 %) ­ with the first degree of osteopenia (average T­score ­ (­1.25) ± 0.04), 9 of them (17.65 %) ­ with the second degree of osteopenia (average T­score ­ (­1.74) ± 0.06), 11 of them (21.57 %) ­ with third degree of osteopenia (average T­score ­ (­2.17) ± 0.02); 12 (23.53 %) women had normal BMD (average T­score ­ (­0.7) ± 0.07). The results of hand bone X­ray densitometry among all patients with SLE showed changes in bone mineral density. 20 (39.22 %) women were diagnosed with osteoporosis (average T­score ­ (­3.03) ± 0.08); 23 (45.09 %) women ­ with osteopenia (average T­score ­ (­2.01) ± 0.08), 4 of them (7.84 %) ­ with the first degree of osteopenia (average T­score ­ (­1.2) ± 0.11), 19 of them (37.25 %) ­ with the third degree of osteopenia (average T­score ­ (­2.18) ± 0.03); 8 women (15.69 %) had normal BMD (average T­score ­ (­0.38) ± 0.01). The results of lumbar spine bone density test employing dual­energy X­ray absorptiometry (DXA) were as follows: 16 (31.37 %) patients with SLE were diagnosed with osteoporosis (average T­score ­ (­3.14) ± 0.13); 21 (41.18 %) patients were diagnosed with osteopenia (average T­score ­ (­1.56) ± 0.13), 10 of them (19.61 %) ­ with the first degree of osteopenia (average T­score ­ (­1.14) ± 0.03), 7 of them (13.73 %) ­ with the second degree of osteopenia (average T­score ­ (­1.70) ± 0.07), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.35) ± 0.03); 14 patients (27.45 %) had normal levels of BMD (average T­score ­ (­0.36) ± 0.15). The results of proximal femur bone density test employing DXA were as follows: only 12 (23.53 %) patients with SLE were diagnosed with osteopenia (average T­score ­ (­1.28) ± 0.08), 5 of them (9.80 %) ­ with the first degree of osteopenia (average T­score ­ (­1.03) ± 0.03), 3 of them (5.86 %) ­ with the second degree of osteopenia (average T­score ­ (­1.65) ± 0.04), 4 of them (7.84 %) ­ with the third degree of osteopenia (average T­score ­ (­2.05) ± 0.03); 39 patients (76.47 %) had normal levels of BMD (average T­score ­ (0.2) ± 0.14). The findings demonstrate direct correlation between T­score results obtained by ultrasound heel bone densitometry and T­score results obtained by lumbar spine DXA (r = 0.72, p < 0.001) as well as T­score results obtained proximal femur DXA (r = 0.38, p < 0.05). The findings also indicate direct relationship between the results of BMD tests employing hand bone X­ray densitometry and lumbar spine DXA (r = 0.56, p < 0.001) as well as proximal femur DXA (r = 0.37, p < 0.05). There is also direct correlation between the results of the BMD tests obtained by ultrasound heel bone densitometry and X­ray hand bone densitometry (r = 0.7, p < 0.001). Both ultrasound heel bone densitometry and X­ray hand bone densitometry identified 89.0 % of patients who had lowered BMD levels according to the results of lumbar spine DXA and 100.0 % of patients who had lowered BMD levels according to the results of proximal femur DXA (sensitivity – 0.89 and 0.1 respectively). Ultrasound densitometry demonstrated higher specificity compared to X­ray osteodensitometry: it identified 57.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 31.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,57 and 0,31 respectively). X­ray osteodensitometry identified 29.0 % of the patients who had normal BMD levels according to the results of lumbar spine DXA and 21.0 % of the patients who had normal BMD levels according to the results of proximal femur DXA (specificity ­ 0,29 and 0,21, respectively). Conclusions. The study demonstrated that both ultrasound heel bone densitometry and X­ray hand bone densitometry are highly sensitive compared to dual­energy X­ray absorptiometry and acceptable methods for diagnosis of osteoporosis in patients with SLE.

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Authors: T. Butovа

Introduction. Postmenopausal women ­ one of the most critical periods in which modern woman spends a third of her life, and therefore the study of this problem is of particular interest. Today is proved the activity of steroidogenic ovarian function in postmenopausal women. It is known that one of the most biologically active forms of testosterone in men and women, which is formed from testosterone directly into the cells “respective authorities target” is dihydrotestosterone (DHT). It is also reported that testosterone may be involved in metabolic disorders glucose in healthy women and about the relationship between high levels of free testosterone incidence of type 2 diabetes mellitus (DM). The presence of the relative hyperandrogenemia may be related to the risk of cardiovascular diseases in postmenopausal women. However, despite the numerous studies of the peculiarities of androgens in the female body, until now this issue has not received its final decision. The aim of the study was to find out the features of the contents of DHT levels in postmenopausal women according to the comorbid diseases DM type 2 and hypertension (HT). Materials and methods. The study involved 137 females aged 45­60 years. Patients were stratified into three groups: 30 patients with type 2 DM (1st group), 34 patients with HT (2nd group), 42 patients with type 2 DM and HT (3rd group). Control of group ­ 31 postmenopausal women without the disease. In blood serum using ELISA methods were tested folitropin, DHT and concentration glucose and glycosylated hemoglobin (НbА1с). Results and discussion. Found that in patients with HT in postmenopausal was observed a statistically significant increase in the concentration preprandial glycemia and content НbА1с, DHT levels compared to women with postmenopausal without the disease. Joining hypertension in patients with type 2 DM accompanied by more pronounced, statistically significant increase of preprandial glycemia and НbА1с and most statistically significant DHT. Among indicators of glucose concentration, НbА1с DHT levels and there is a direct correlation, indicating a direct positive indicators of glucose dependence concentration in blood and the content НbА1с, DHT. Conclusions. In patients with HT in postmenopausal was observed a statistically significant increase in DHT concentrations in the blood compared to women with postmenopausal without the disease. At the same time in patients with type 2 DM, compared to patients with HT verified a clear increase in the content of DHT in the blood. Thus, to forecast the possibility of type 2 DM and comorbid HT during examination in postmenopausal women, should be considered the level of serum DHT.

53-59

Authors: S. Nyankovskyy, R. Furtak, M. Yatsula, O. Shpychka

Introduction. Respiratory system diseases were and continue to be a topical problem of the medicine overall and pediatrics in particular. Pneumonia is the most serious disease that kills children under 5 years old globally, taking about 1 million lives every year. Purpose of the study. To analyze the domestic and foreign literary sources of information dedicated to the role of pharmacogenetics in appearances of the severe forms and complications of pneumonia in children and also to describe a clinical case. Materials and research methods. Content­analysis, methods of systemic and comparative analysis, biblio semantic method of the actual scientific researches study about the role of pharmacogenetics in appearence of severe forms and pneumonia complications in children, analysis of a case of the disease of a particular patient who was under our observation. Source searching was done with the scientometric databases of medical information: PubMed­NC­BI, Medline, CochraneLibrary, EMBASE, ResearchGate using keywords: pneumonia, children, pharmacogenetics, xenobiotic biotransformation genes. In all, 41 sources in English, Russian and Ukrainian languages were analyzed. Results of the analysis. Pneumonia is an acute infectious inflammatory disease of the lung parenchyma, characterized by the infiltrative changes in lung tissue and respiratory failure. A lot of microorganisms can be a reason for pneumonia occurrence. Among the most common bacteria pathogens are: Streptococcus pneumoniae, Haemophilus influenzae type B, and among viruses it’s Human respiratory syncytial virus. Despite the timely diagnosis and an appropriate drug therapy the number of severe forms and complications of pneumonia is not being reduced. A lot of scientific studies of this topic during the last years are aimed at genetics exploration. Particularly, the area of pharmacogenetics is interesting and perspective part of it. About 50 % of adverse responses to drugs are caused by the genetic factors. Study of pharmacogenetic impact can serve as a basis for a creation of the individualized approach to the choice of treatment tactics and to the dosage regime. Genetic polymorphisms of xenobiotic metabolism determines the division of people into groups that differ in their ability to metabolize drugs from insufficient to ultrafast metabolisers. Genetic polymorphisms of xenobiotic metabolism can be the reason for occurrence of severe forms and complications of various diseases, including pneumonia in children. These genes include: glutathione transferases (GSTM), O­ and N­acetyltransferases (OAT, NAT1, NAT2) and others. Among the proteins which affect the speed of excretion of the pharmacological agents the special place belongs to P­glycoprotein, encoded by the gene MDR1. The research results of different authors showed that genetic polymorphism of MDR1 can be an important factor that determines the predisposition to various diseases and resistance to treatment. Conclusions. The researches of genes involved in the distribution, biotransformation and excretion of toxic products of decay of drugs, is a promising and important component of the pathogenesis and, accordingly, the diagnosis and treatment of pneumonia in children.