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Functional analysis of endothelial dysfunction in mice aorta following high-fat diet administration
Martínková, Adéla ; Němečková, Ivana (advisor) ; Vitverová, Barbora (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Supervisor: RNDr. Ivana Němečková, Ph.D. Author: Adéla Martínková Title of Thesis: Functional analysis of endothelial dysfunction in mice aorta following high-fat diet administration Background and aim: Endothelial dysfunction is associated with the impairment of vasodilatory response of vessel wall mediated by nitric oxide which is produced by endothelial cells under physiological conditions. Endothelial dysfunction can be induced by high fat diet (HFD) feeding in experimental animals. The aim of this diploma thesis was to determine the effect of HFD on the functional parameters of aorta, especially the effect of the vasodilatory factor acetylcholine on endothelial cells of the thoracic part of the mouse aorta. Methods: The 7 months old C57BL/6J male mice were fed high fat diet containing 42 % kcal fat for 12 weeks to induce endothelial dysfunction in the aorta. The control group was fed a standard laboratory diet during the whole experiment. Functional parameters of aorta were assessed with wire myograph 620M. Results: At the end of the experiment, the weight of the animals was statistically significantly lower in the HFD group compared to the control group of mice fed the standard...
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Histological analysis of selected markers in cardiometabolic diseases 2
Zemánková, Lucie ; Vitverová, Barbora (advisor) ; Němečková, Ivana (referee)
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease of the liver tissue. More advanced stages of NAFLD are characterized by the development of fibrosis. The fibrotic process occurs at the stage of nonalcoholic steatohepatitis and is usually accompanied by inflammation. The aim of this study was to analyze the expression of fibrosis markers (α - SMA, galectin - 3 and collagen). As part of the study design, mice were divided into two groups, namely a control group fed a standard laboratory diet (chow diet) and an experimental group fed a CDAA diet. CDAA diet leads to the development of fibrosis through inhibition of fatty acid oxidation in hepatocytes, increase in lipid synthesis and development of oxidative stress and inflammation. Mice were fed for 4 weeks. The expression of selected fibrosis markers was detected and evaluated by indirect immunohistochemistry using the ABC method. The results of this thesis show that α-SMA marker positivity was stronger in the experimental model and was also detected in activated hepatic stellate cells and myofibroblasts in the liver. Galectin-3 staining was also more pronounced in the experimental group than in the control group. Sirius Red staining for the detection of collagen fibers was also more intense in the experimental group, where the analysis...
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Histological analysis of selected markers in cardiometabolic diseases 1
Bůtorová, Kateřina ; Vitverová, Barbora (advisor) ; Němečková, Ivana (referee)
Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of excess fat in the liver that is not accompanied by excessive alcohol consumption. In the first stage, there is a simple fatty liver (steatosis) due to excessive fat deposition in the liver cells. As the disease progresses, there is the development of an inflammatory response and the transition to non-alcoholic steatohepatitis. The aim of this study was to evaluate whether there is the development of an inflammatory response and endothelial dysfunction after administration of a CDAA diet. To clarify this hypothesis, the analysis of VCAM-1, ICAM-1, and endoglin expression was selected. In this study, male C57BL/6 mouse model was used. The control group was fed a standard laboratory diet, and the experimental group received the CDAA diet to induce NAFLD for 4 weeks. Administration of the CDAA diet reduces the oxidation of fatty acids in hepatocytes, increases lipid accumulation, induces oxidative stress, and causes steatosis and the development of inflammation in liver tissue. The expression of selected markers of inflammation and endothelial dysfunction was detected using indirect immunohistochemistry. The results of this study showed a significant difference in the expression of the proinflammatory VCAM-1...
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Functional analysis of endothelial dysfunction in mice aorta following high-fat diet administration
Martínková, Adéla ; Němečková, Ivana (advisor) ; Vitverová, Barbora (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Supervisor: RNDr. Ivana Němečková, Ph.D. Author: Adéla Martínková Title of Thesis: Functional analysis of endothelial dysfunction in mice aorta following high-fat diet administration Background and aim: Endothelial dysfunction is associated with the impairment of vasodilatory response of vessel wall mediated by nitric oxide which is produced by endothelial cells under physiological conditions. Endothelial dysfunction can be induced by high fat diet (HFD) feeding in experimental animals. The aim of this diploma thesis was to determine the effect of HFD on the functional parameters of aorta, especially the effect of the vasodilatory factor acetylcholine on endothelial cells of the thoracic part of the mouse aorta. Methods: The 7 months old C57BL/6J male mice were fed high fat diet containing 42 % kcal fat for 12 weeks to induce endothelial dysfunction in the aorta. The control group was fed a standard laboratory diet during the whole experiment. Functional parameters of aorta were assessed with wire myograph 620M. Results: At the end of the experiment, the weight of the animals was statistically significantly lower in the HFD group compared to the control group of mice fed the standard...
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Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration
Široká, Veronika ; Nachtigal, Petr (advisor) ; Vitverová, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration Author: Veronika Široká Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of this diploma thesis was to analyze changes in the expression of endoglin and markers of inflammation VCAM-1 and ICAM-1 in liver in an experimental mouse model of liver fibrosis, which was induced by administration of a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC). Another aim was to elucidate the effect of carotuximab administration on the expression of these markers after fibrosis induction, and to determine whether carotuximab administration effects the process of liver fibrosis by endoglin inhibition. Methods: The experimental mice were divided into three groups - the control group, which was fed a standard (chow) diet, the DDC group, which was fed a DDC-supplemented diet, and the DDC/TRC105 group, which was administrated by carotuximab along with the DDC diet. Liver tissue samples from all three groups were subjected to histochemical staining to detect steatosis (light microscopy) and indirect...
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Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration
Široká, Veronika ; Nachtigal, Petr (advisor) ; Vitverová, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Immunohistochemical analysis of endoglin expression and biomarkers of inflammation during liver fibrosis after Carotuximab administration Author: Veronika Široká Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of this diploma thesis was to analyze changes in the expression of endoglin and markers of inflammation VCAM-1 and ICAM-1 in liver in an experimental mouse model of liver fibrosis, which was induced by administration of a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC). Another aim was to elucidate the effect of carotuximab administration on the expression of these markers after fibrosis induction, and to determine whether carotuximab administration effects the process of liver fibrosis by endoglin inhibition. Methods: The experimental mice were divided into three groups - the control group, which was fed a standard (chow) diet, the DDC group, which was fed a DDC-supplemented diet, and the DDC/TRC105 group, which was administrated by carotuximab along with the DDC diet. Liver tissue samples from all three groups were subjected to histochemical staining to detect steatosis (light microscopy) and indirect...
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Soluble endoglin role in the pathogenesis of endothelial dysfunction
Vitverová, Barbora ; Nachtigal, Petr (advisor) ; Vrablík, Michal (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: Msc. Barbora Vitverova Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Soluble endoglin role in the pathogenesis of endothelial dysfunction The endothelium is a major regulator of vascular homeostasis and exerts a number of vasoprotective effects, including production of vasodilating agents, suppression of smooth muscle cell growth, or inhibition of inflammatory responses. Most of these effects are mediated by nitric oxide (NO), the most effective endogenous vasodilator. Decreased NO production or its activity is a hallmark of endothelial dysfunction leading to an impaired endothelial-dependent vasodilation. Endothelial dysfunction is the first and key step in the development of atherosclerosis and can be detected before structural changes in the vessel wall. Atherosclerosis is a complex inflammatory disease underlying many cardiovascular disorders including ischemic heart disease and represents the major cause of morbidity and mortality in developed countries. Statins are drugs of choice in the treatment of atherosclerosis and ischemic heart disease, which have been shown to reduce LDL cholesterol levels and modulate endothelial function with their...
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Soluble endoglin role in the pathogenesis of endothelial dysfunction
Vitverová, Barbora ; Nachtigal, Petr (advisor) ; Vrablík, Michal (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: Msc. Barbora Vitverova Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Soluble endoglin role in the pathogenesis of endothelial dysfunction The endothelium is a major regulator of vascular homeostasis and exerts a number of vasoprotective effects, including production of vasodilating agents, suppression of smooth muscle cell growth, or inhibition of inflammatory responses. Most of these effects are mediated by nitric oxide (NO), the most effective endogenous vasodilator. Decreased NO production or its activity is a hallmark of endothelial dysfunction leading to an impaired endothelial-dependent vasodilation. Endothelial dysfunction is the first and key step in the development of atherosclerosis and can be detected before structural changes in the vessel wall. Atherosclerosis is a complex inflammatory disease underlying many cardiovascular disorders including ischemic heart disease and represents the major cause of morbidity and mortality in developed countries. Statins are drugs of choice in the treatment of atherosclerosis and ischemic heart disease, which have been shown to reduce LDL cholesterol levels and modulate endothelial function with their...
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Evaluation of elastic recovery of tablets containing theophylline
Vitverová, Barbora ; Šklubalová, Zdeňka (advisor) ; Ondrejček, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: Doc. PharmDr. Šklubalová Zdeňka, Ph.D. Student: Barbora Vitverová Title of Thesis: Evaluation of elastic recovery of tablets containing theophylline This diploma thesis deals with evaluation of elastic recovery of tablets containing theophylline. The axial and radial elastic recovery is evaluated. Used materials are characterized in a theoretical part. It concerns microcrystalline cellulose Comprecel 102, lactose SpheroLac 100, calcii hydrogenphosphas anhydrous Di- Cafos A150, calcii hydrogenphosphas dihydrate Di-Cafos D160, magnesii stearas and theophylline. Further, compression process and its evaluation are described and also the elastic recovery of tablets after compression, its calculation and factors which can influence it. The experimental part of thesis deals with the elastic recovery of tablets. The tablets were compressed by compression strength 10 kN and the height and diameter were measured after 0, 3, 6 and 24 hours after compressing. The elastic recovery of tablets was calculated from these values. The dimensions of tablets at the maximal compression strength 10 kN were used as the initial values. From results is obvious that the highest elastic recovery is...
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