After single and repeated peroral administration of bemitil to rats this drug was found in the liver, brain, kidneys, spleen, heart, skeletal muscles, lungs, adipose tissue, and testicles. After single treatment accumulation of bemitil was most pronounced in the liver. After repeated treatment the decrease in bemitil concentration in the liver was probably associated with increased elimination of the drug from liver tissue due to intensification of its biotransformation. We conclude that bemitil can accumulate in the blood, but not in tissues.
We studied experimental kinetics of ethomerzol (5-ethoxy-2ethylthiobenzimidazole hydrochloride) distribution in the liver, brain, kidneys, spleen, heart, skeletal muscles, lungs, adipose tissue, and testes of rats after its single or course administration. Peculiarities of ethomerzol distribution in various administration regimens were analyzed. Single treatment led to more pronounced accumulation of the drug in the liver. Study of ethomerzol distribution after course treatment revealed organs and tissues accumulating the drug (blood, brain, heart, kidneys, lungs, and adipose tissue).
Comparative study of experimental kinetics of distribution of benzimidazole derivatives (bemithyl, etomerzole, and thietazole) in organs and tissues was carried out after single and course treatment. The drugs intensely passed into organs and tissues from the blood after treatment by all protocols. Specific features of drug distribution were detected; for example, splenic tissue selectively accumulated thietazole during course treatment.
Introduction. According to the analysis of indicators of the hemostasis system in liver pathology, there are multidirectional data in the literature, which may be associated with the examination of patients with varying degrees of severity and etiology of the process. Aim. The aim of the study was to study the indicators of hemostasis and markers of endothelial damage in patients with non-alcoholic steatosis and liver fibrosis of viral etiology. Materials and methods. A total of 64 people were examined. The first group included 32 patients with non-alcoholic liver steatosis on the background of obesity of 1–2 degrees, with an average age of 46.3 ± 4.3 years (12 men and 20 women). The second group consisted of 22 patients with liver fibrosis on the background of chronic hepatitis C (HCV) with an average age of 36.8 ± 4.7 years (12 men and 10 women). The control group included 10 practically healthy individuals with an average age of 38.9 ± 5.3 years without liver pathology. The number of platelets, platelet aggregation with ADP inducers, collagen and ristocetin, functional activity of Willebrand factor (vWF), coagulation hemostasis and fibrinolysis system, and serum concentration of vascular endothelial growth factor (VEGF) were determined. Statistical processing of the obtained data was carried out using the program “Stat2015”. Results. Induced platelet aggregation in steatosis and liver fibrosis significantly decreased with ADP agonists and collagen against the background of a normal platelet count. In both study groups, signs of endothelial damage with a tendency to increase the functional activity of vWF and VEGF hyperproduction were found. An elongation of thrombin time was also recorded, more significantly in patients with steatosis. Conclusion. Patients with non-alcoholic liver steatosis and liver fibrosis on the background of HCV are characterized by disorders in the vascular-platelet (endothelial damage and thrombocytopathy in the form of platelet hypocoagulation) and coagulation (hypocoagulation) links of hemostasis.
The aim. To study risk factors, clinical features, anthropometric, biochemical and metabolic parameters, parameters of the functional state of the endothelium, the level of interleukin-6 (IL-6) and markers of hemostasis in patients with non-alcoholic liver steatosis in the early postmenopausal period living in Perm. Materials and methods. 100 women in the early postmenopausal period were examined: 70 patients with the clinical form non-alcoholic liver steatosis and overweight or obesity of varying severity (49.9±1.1 years) and 30 practically healthy women without obesity and liver pathology (47.3±2.6 years). Biochemical parameters, lipid spectrum, insulin, leptin, leptin receptors, interleukin-6 (IL-6), markers of endothelial dysfunction, hemostasis parameters were determined in the blood of all subjects, body mass index (BMI), free leptin index, NOMA-IR and Caro were calculated. Liver steatosis was determined by ultrasound examination. Results. General weakness (35%), severity (35%) and pain (15%) in the right hypochondrium (35%), dyspepsia - belching (25%), nausea (15%), heartburn (10%), flatulence (10%). Hypertension was observed in 60% of women, type 2 diabetes mellitus - in 24%. All patients had a genoid type of obesity. 34% of women with non-alcoholic liver steatosis were overweight, 29% were obese of the 1st degree, 23% were obese of the 2nd degree, and 14% of patients were obese of the 3rd degree. Conclusion: In the examined women with non-alcoholic liver steatosis in the early postmenopausal period living in Perm, risk factors for the development of obesity were identified: consumption of high-calorie foods with high fat and sugar content and hypokinesia, and the course of the disease was accompanied by the development of dyslipidemia, insulin and leptin resistance, inflammatory syndrome with activation of proinflammatory cytokine IL-6 and hyperfibrinogenemia, and also endothelial dysfunction, the severity of which increased during the transition from 1 to 2-3 degrees of obesity.
Objective. To evaluate the severity of the inflammatory syndrome by the serum concentration of proinflammatory cytokines of tumor necrosis factor alpha (TNF-) and interleukin-6, endothelial dysfunction syndrome (ED) by the level of vasculoendothelial growth factor (VEGF) and the functional activity of Willebrand factor (WF) in the blood of patients with nonalcoholic liver steatosis (NALS) and liver fibrosis (LF) of viral genesis. Materials and methods. 52 patients with NALS and 27 patients with LF of viral etiology (hepatitis C) were examined. The control group included 20 practically healthy individuals. The concentrations of TNF-, IL-6 and VEGF were determined in the blood by enzyme immunoassay. The functional activity of WF was measured by the level of aggregation with the inducer ristocetin using laser aggregometer. Results. According to the results of ELISA, an increase in serum levels of proinflammatory cytokines TNF- and IL-6 was registered in patients of both study groups in comparison with the control, being more pronounced in patients with viral LF. Hyperproduction of VEGF was observed in both groups of patients, and the concentration of this marker was significantly higher in viral LF than in patients with NALS (p = 0.002). The functional activity of WF in patients with NALS and in the group with LF also significantly exceeded the control values, but there were no significant differences between the nosological forms (p = 0.675). Conclusions. The course of NALS and viral LF is characterized by the development of an inflammatory syndrome and ED, associated with an increase in the production of proinflammatory cytokines TNF- and IL-6 and hyperproduction of VEGF, more pronounced in LF. The functional activity of WF also increases in both nosological forms, but without significant differences.
Introduction. Non-alcoholic fatty liver disease (NAFLD) increases with age. The main risk factor for NAFLD and the progression of liver fibrosis is obesity. However, the disease also occurs in 7% of people with normal body weight, mainly in young women with normal levels of liver enzymes, in whom liver disease can nevertheless progress.Aim. To assess the features of clinical and laboratory manifestations of non-alcoholic hepatic steatosis (NASP) in women of reproductive age and in menopause, depending on the degree of obesity.Materials and methods. We examined 86 women with NAS and obesity, of which 49 were women of reproductive age (37.3 ± 1.7 years) and 37 patients in menopause (51.3 ± 1.0 years). Determined: transaminases, total bilirubin, glucose, lipid spectrum, insulin, leptin, interleukin-6 (IL-6), vasculoendothelial growth factor (VEGF); body mass index (BMI), atherogenicity index (AI), and HOMA-IR index were calculated. Liver steatosis was determined by ultrasound, fibrosis was excluded by fibroelastography.Results. The clinic in both groups of women was poor; there were no signs of liver fibrosis. In women with liver steatosis with concomitant obesity in reproductive age and menopause, dyslipidemia, hyperleptinemia, increased levels of IL-6 and signs of endothelial damage in the form of VEGF hyperproduction are recorded. At the same time, dyslipidemia and hyperleptinemia are significant in menopause, and in women with steatosis at reproductive age, signs of endothelial damage are more pronounced.Conclusion. In both groups of women with the clinical form of NASP, most of the studied laboratory parameters marked the transition to stage 1 obesity, leptin made it possible to differentiate almost all degrees of obesity, and the production of IL-6 and VEGF significantly increased at stages 2–3 of obesity.
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