ASSOCIATIONS OF POLYMORPHISMS NOS3-T-786C, MTHFR-C667T, P2RY12-T-744C, (GPIBα) -C482T AND GENE INTERACTIONS IN MACROANGIOPATHIES IN PATIENTS WITH COMBINED HYPERTENSION AND TYPE DIABETES MELLITUS 2.

OBJECTIVE: The aim: To establish the role of allelic polymorphisms NOS3-T-786C, MTHFR-C667T, P2RY12--744C, (GPIbα)-C482T in the development of vascular lesions in patients with hypertension and diabetes mellitus type 2. PATIENTS AND METHODS: Materials and methods: The study included 100 patients with hypertension and diabetes mellitus type 2 (main group) and 50 patients without type 2 diabetes (control group). Patients underwent echocardiography, color duplex scanning of extracranial, brachiocephalic and femoral vessels. The distribution of allelic polymorphisms was investigated by isolation DNA from leukocytes and polymerase chain reaction (PCR). RESULTS: Results: The risk of vascular damages increases 2-fold when carrying all 4 risk alleles in monozygotic genotypes of polymorphic loci in patients with hypertension with concomitant type 2 diabetes (p<0,05). In gene-gene interaction, the values of contributions and directions of interaction between alleles of polymorphic loci are established (p<0,05). Genes create a paired hierarchy of interaction according to their functional activity; the largest contribution to the probable vascular damage depends on the allelic polymorphism NOS3-786CT (p<0,05), the lowest - on the allelic polymorphism P2RY12-744CC (H2H2). The genetic polymorphism of the MTHFR gene is independent of the influence of other studied polymorphisms (p<0,05); the genes P2RY12-744CT and GPIbα 482CT act synergistically with the gene NOS3-786CT, being in a weak negative interaction with each other. CONCLUSION: Conclusions: Phenotypic manifestations of endothelial dysfunction may be modified by allelic polymorphism of genes associated with endothelial and platelet functions with the risk of vascular complications.

The relationship between prolactin levels and the results of holter monitoring in patients with stable angina of tension and gastroesophageal reflux disease.

OBJECTIVE: The aim: Determine the possible relationship between prolactin levels and the results of Holter monitoring in patients with stable angina of tension and gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: Materials and methods: The study included 118 patients with stable angina of tension of I-II functional class. Of these, 88 patients with stable angina of tension with comorbid GERD (A, B, C), who were included in the second group of the study and 30 patients with isolated stable angina of tension which formed the 1st group. All patients who were included in the study prior to treatment were evaluated for serum prolactin levels and Holter monitoring. RESULTS: Results: In patients with stable angina of tension and GERD, prolactin levels exceed the norm levels and are higher than the level of prolactin in the group with isolated stable angina (p<0,05), as well as the number of episodes of painful and painless myocardial ischemia and their duration (p<0,05). The presence of a comorbidity with GERD provokes an increase in the total duration of episodes of ischemia per day in patients with stable angina compared to those in patients with no GERD. A direct linear relationship was founded between prolactin serum levels and the number of episodes of pain in myocardial ischemia in patients with stable angina and GERD per day, and between the total duration of episodes of myocardial ischemia and prolactin levels. CONCLUSION: Conclusions: In patients with stable angina and GERD, in 70.4% of cases, the level of prolactin exceeds the norm in 2,6 times, and is higher than the level of prolactin in the isolated group of stable angina. For the comorbidity of stable angina and GERD, the number of episodes of painful, painless myocardial ischemia and their duration is more than once in the group of patients with stable angina without GERD (p<0.05).

Features of some anthropometric indices and indices of insulin resistance in patients with non-alcoholic steatohepatitis on the background of obesity and osteoarthritis.

OBJECTIVE: The aim: To estimate the diagnostic and predictive value of anthropometric indices indicating obesity and glycemic parameters in the progression of NASH due to comorbidity with OA and OB. PATIENTS AND METHODS: Materials and methods: 90 patients were examined and distributed into three groups: group 1 included patients suffering from OA, grade II-III according to Kellgren and Lawrense classification, with normal body mass, group 2 -patients with NASH and obesity without OA, group 3 -patients with OA, NASH and obesity. The control group consisted of 30 healthy individuals of the corresponding age. RESULTS: Results: There was a correlation between lipid and carbohydrate metabolism. This fact was confirmed by the evidence that under the influence of IR there was an increase in the level of lipoproteins enriched in triglycerides, the concentration of cholesterol of low density lipoprotein and reduction in level cholesterol of high density lipoprotein, which led to the progression of the clinical course of NASH. It was established that anthropometric indices of patients with comorbid flow of NASH, OA and OB were significantly (p <0.05) higher than in experimental groups. A positive correlation was found between some anthropometric indices and the following glycemic parameters: fasting blood glucose, HOMA-IR suggested that insulin resistance contributed to the growth of glycated compounds leading not only to the progression of NASH and affect the dysfunction of chondrocytes, but also influencing destruction of subchondral bone in osteoarthritis. CONCLUSION: Conclusions: The outcomes of the study result in the necessity of studying the metabolic status in patients with a comorbid progression of NASH, OB and OA for timely correction of the revealed disorders, which will reduce the run of NAFLD.

Pathogenetic role of nitrogen monoxide efficiency of pharmacotherapy in patients with gastroesophageal reflux disease and stable angina of tension.

OBJECTIVE: Introduction: The search for new mechanisms of their interconnection and effective pharmacological correction of gastroesophageal reflux disease (GERD) for comorbidity with stable angina of tension (SAT). The aim: To establish the role of nitrogen monoxide (NO) in the pathogenesis of GERD in patients with SAT and to study the effectiveness of the correction of the basic therapy of SAT in order to eliminate the clinical manifestations of GERD and prevent its development. PATIENTS AND METHODS: Materials and methods: 88 patients with SAT with a comorbid GERD were examined. We determined clinical symptoms, the level of stable NO metabolites, calculated the number of nitroglycerin tablets taken one week. All patients (2 groups) received baseline therapy for GERD and SAT. In this case, the patients of the 2nd group (45 persons) received therapy with the exception of long-acting nitrates and, in addition, meldonium for 30 days. RESULTS: Results:With the exception of the use of nitro-containing drugs and adding to the basic therapy of SAT the drug meldonium we faster (p<0,05) achieved a regression of clinical symptoms of GERD and decrease in the level of metabolites NO molecule in patients with SAT. CONCLUSION: Conclusion: In the case of the exclusion of the intake of long-acting nitrates with the adding of meldonium to the basal therapy of the SAT and the GERD the content of metabolites of nitrogen monoxide in the blood is more normalized, which correlates with a decrease in the frequency of GERD symptoms in patients with SAT and GERD.

The role of endothelial dysfunction in the progression mechanisms of non-alcoholic steatohepatitis in patients with obesity and chronic kidney disease.

OBJECTIVE: Introduction: The study increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates the research into mechanisms of mutual burden and the search for new factors in the pathogenesis of this comorbidity progression . The aim: To establish the role of endothelial dysfunction in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 135 patients were examined: of which 52 patients with non-alcoholic steatohepatitis with obesity I degree (1 group), 53 patients with nonalcoholic steatohepatitis with comorbid obesity of the I degree and chronic kidney disease of the І-ІІ stage (group 2). The control group consisted of 30 practically healthy persons of the corresponding age and sex. The average age of patients was (45.8 ± 3.81) years. RESULTS: Results: The results of the study showed that in patients with NASH, a significant increase in the content of NO in the blood was detected in comparison with the index in PHP (p <0,05) in group 1 - in 2,1 times, in the 2nd group - in 2,6 times (p <0,05). The role of nitrosative stress in the pathogenesis of NASH was proved, the confirmation of which is the increase in the concentration of nitrosothiols, peroxynitrite and other metabolites NO in the blood. Increased peroxynitrite formation due to the generation of NO by leukocytes is an important aspect of the damaging effect and inflammation process in NASH. Pathological hyperproduction of NO by endothelial cells and leukocytes from inflammatory infiltrates in the liver contributes to the development of nitrosative stress in NASH. The established hypernitrate in blood may also be considered compensatory in response to hyperproduction of ET-1 in all observational groups. CONCLUSION: Conclusions: Confirmation of the presence of endothelial dysfunction (ED) in patients with NASH with CKD resulted in a probable growth of the number of desquamated endothelial cells (DEC) in the 2nd group of patients in 1.9 times (p2 <0.05). Generation by neutrophils during the exacerbation of NASH of a significant number of active forms of oxygen and nitrogen and hyperproduction of endothelial cells and endometrial lymphocytes with progressive damage to the endothelium (growth of DEC) leads to significant ED, accompanied by mosaic angiospasm of the arteries due to hyperproduction of ET-1 and parectic vasodilatation of the veins of the portal vein system because of the hyperproduction of NO.

The role of hydrogen sulfide in the progression of chronic obstructive pulmonary disease in patients with non-alcoholic steatohepatitis

Introduction: The steady increase in the incidence of comorbidity of chronic obstructive pulmonary disease and non-alcoholic steatohepatitis against the background of obesity in people of working age in Ukraine and in the world stipulates the need of investigation of the mechanisms of interconnection and the search for new factors of the pathogenesis of progression of this comorbid pathology. Attention to the role of hydrogen sulfide in the development of fibrosis has only been recently paid. The aim: To establish the role of hydrogen sulfide in the mechanisms of progression of chronic obstructive pulmonary disease and non-alcoholic steatohepatitis against the background of obesity. Material and methods: Materials and methods: 100 patients with chronic obstructive pulmonary disease have been examined, including 49 with non-alcoholic steatohepatitis and obesity of the 1st stage: group 1 ­ 28 patients with chronic obstructive pulmonary disease (2B GOLD); group 2 ­ 23 patients with chronic obstructive pulmonary disease (3C, D); group 3 ­ 25 patients with chronic obstructive pulmonary disease (2B) with non-alcoholic steatohepatitis; group 4 ­ 24 patients with chronic obstructive pulmonary disease (3C, D) and non-alcoholic steatohepatitis. The average age of patients was (47.3±3.1) years. There were 20 apparently healthy persons of the corresponding age and sex in the control group. Results: The received data confirm that patients with chronic obstructive pulmonary disease secondary to non-alcoholic steatohepatitis, which developed against the background of obesity, suffer from a significant increase in the synthesis of collagen and glycoproteins, accompanied by an ineffective resorption of newly formed collagen due to insufficient activation of collagenolysis and proteolysis, a significant imbalance in the connective tissue metabolism system, which leads to progressive fibrosis of the lungs and liver and disturbances of their functions. This was caused by the disorder of H2S homeostasis, confirmed by the data of correlation analysis. Conclusions: Patients with chronic obstructive pulmonary disease and non-alcoholic steatohepatitis, which developed against the background of obesity, are characterized by a significant increase in the synthesis of collagen and glycoproteins, which was accompanied by an ineffective resorption of newly formed collagen against the background of substantial activation of proteinase inhibitors (α2-MG), accompanied by the hyperproduction of nitrogen monoxide, endothelin-1, hyperlipidemia, deficiency of hydrogen sulfide liberation.

Clinical and pathogenetic features of nonalcoholic steatohepatitis for comorbidity with bronchial asthma on the background of obesity.

OBJECTIVE: Introduction: The comorbid flow of non-alcoholic steatohepatitis (NASH) and bronchial asthma (BA) on the background of obesity is often recently drawn to the attention of both practitioners and researchers . The aim of our study was to study the changes in the functional state of the liver and the dependence of the external respiration function in patients with non-alcoholic steatohepatitis in combination with bronchial asthma and obesity. PATIENTS AND METHODS: Materials and methods: The study was attended by 50 people aged from 30 to 50 years (average age 42 years), of which 40% were men and 60% women. Of these, 30 patients with obesity I degree (BMI greater than 30 kg / m2) non-alcoholic steatohepatitis was detected, and in 20 of patients, non-alcoholic steatohepatitis was combined with obesity of the I degree and persistent bronchial asthma of moderate severity. Duration of the disease was from 2 to 6 years. The control group consisted of 20 practically healthy persons (PHPs) of the corresponding age and sex. RESULTS: Results: In patients with NASH with comorbid BA and obesity I degree there are more noticed syndromes of cytolysis and cholestasis, mesenchymal inflammation, more significant changes in the liver, as evidenced by the low AST/ALT ratio in this group. Patients with non-alcoholic steatohepatitis on the background of obesity of the I degree with the addition of bronchial asthma of moderate severity and the persistent flow at the exacerbation phase, the content in the blood of markers of the activity of cytolysis of hepatocytes increases (increased activity of aminotransferases serum, p <0,05), cholestasis (increased contentof direct bilirubin in the blood, p <0,05, cholesterol activity, p<0,05, gamma-glutamyltransferase activity, p <0,05 and alkaline phosphatase, p <0,05) and mesenchymal inflammation (increase in the thyme test, p <0,05), which testifies to the aggravating factor and the impact of BA on the course of NASH. CONCLUSION: Conclusion: The presence of visceral obesity and nonalcoholic steatohepatitis in patients with bronchial asthma leads to the accumulation of its clinical course, the deepening of changes in the function of external respiration by obstructive type (a possible decrease in FEV1 and PEF, p<0.05). The presence of obesity and NASH contributed to the development of restrictive type of respiratory insufficiency in the form of a possible decrease in Vital capacity (VC, p<0,05) in patients without BA, and in patients with NASH and obesity with BA, which significantly aggravated its course.

The role of hydrogen sulfide in the progression mechanisms of non-alcoholic steatohepatitis and chronic kidney disease.

OBJECTIVE: Introduction: The steady increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine. The aim: To establish the role of hydrogen sulfide in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 114 patients with NASH were examined on the background of obesity of І-ІІ degree, including: 52 patients with NASH (group 1) (without accompanying CKD), 62 patients with NASH with a comorbid CKD І-ІІ degree (group 2). The control group consisted of 20 practically healthy persons (PHPs) of the corresponding age and sex. RESULTS: Results: The obtained data testify that a significant increase in the synthesis of collagen and glycoproteins in patients with NASH, which arose on the background of obesity, that comorbid with CKD, which was accompanied by an ineffective resorption of newly formed collagen due to insufficient activation of collagenolysis and proteolysis, a significant imbalance in the system of connective tissue metabolism. CONCLUSION: Conclusions: A significant increase in the synthesis of collagen and glycoproteins (fibronectin) in patients with NASH, which was observed on the background of obesity, was established, which is accompanied by an ineffective resorption of newly formed collagen due to inhibition of collagenolysis against activation of proteinase inhibitors (α2-MG).