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Genetic determination of cholesterolemia regulation
Vlachová, Miluše ; Kovář, Jan (advisor) ; Vrablík, Michal (referee) ; Kazdová, Ludmila (referee)
Most types of hypercholesterolemia are of polygenic origin. Some genes related to hypercholesterolemia are known, although all genes responsible for cholesterolemia regulation have not been characterised yet. To identify these new genes, animal models with spontaneous defects in cholesterol metabolism could be very useful. Moreover, a number of variations and polymorphisms have been found to influence blood cholesterol levels in humans. Some may also affect cholesterolemia responsiveness to dietary fat. The Prague hereditary hypercholesterolemic (PHHC) rat is a unique model of hypercholesterolemia induced by dietary cholesterol alone (without administration of cholic acid or thyrotoxic drugs). It exhibits modestly increased cholesterolemia when fed chow and responds to a diet containing cholesterol with a several-fold increase of cholesterolemia to concentrations comparable to those observed in hypercholesterolemic patients. Hypercholesterolemia in this model is characterised by accumulation of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) enriched by cholesterol. In an experiment with tyloxapol (an inhibitor of lipoprotein lipase) we found that PHHC rats on a cholesterol diet incorporated twice as much cholesterol into VLDL as Wistar rats, although liver...
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Analysis of selected genetic markers in patients after heart transplant
Petříková, Nikola ; Hubáček, Jaroslav (advisor) ; Vrablík, Michal (referee)
Heart transplantation is performed in patients with end-stage heart failure, in whom all other methods of treatment failed. The most common causes of end-stage heart failure are dilated cardiomyopathy and coronary artery disease. The destiny of these patients is highly variable. Prediction of long term survival in patients after heart transplantation is not satisfactory and up to now has not been found reliable marker. Most of the patients die after heart transplantation due to cardiovascular disease. This thesis is focused on molecular genetics and statistical analysis of four single nucleotide polymorphisms, namely rs17817449 (16q12.2, FTO gene), rs2943634 (2q36.3; intergenic region), rs6922269 (6q25.1; MTHFD1L gene), and rs10757274 (9p21.3; intergenic region). According to genome wide association studies are these SNPs assosiated with cardiovascular diseases. We genotyped DNA samples of 364 heart donors and 364 heart recipients. The results were statistically compared (using OR and Pearson's χ2 test) with the control group, which consisted of samples of individuals from the general population MONICA study. We examined the genotype in patients whose hearts failed due to dilated cardiomyopathy or coronary artery disease and then in patients with cardiac allograft vasculopathy. Furthermore, we focused on...
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Evaluation of animal fat consumption of patients with cardiovascular disease, diabetes mellitus
Šťovíčková, Jana ; Vrablík, Michal (advisor) ; Šnejdrlová, Michaela (referee)
This bachelor's thesis is focused on animal fat consumption of patients with cardiovascular disease (CVD) and diabetes mellitus (DM). Content of thesis is divided into theoretical and practical part. The main objective of theoretical part is to provide a general description of lipids in terms of distribution, structure, characteristics and their role in human organism. In the following chapters metabolism and transport of lipids is described with more attention to details. The last part of theoretical part deals with animal fats in nutrition, mostly risk factors as a consequence of their increased consumption, and dietary measures as a prevention and therapy of CVD and DM. The practical part of bachelor's thesis is based on assessment survey. The object of this survey was the evaluation of eating habits, mainly the measure of animal fats consumption of patients with CVD and DM. Next object of interest was the evaluation of awareness, knowledge and education these patients have about dietary measures in relation to their disease. Question about the way how are these measures followed by patients was also examined. The survey was conducted in the diabetological center and also in the centre of preventive cardiology of General Teaching Hospital in Prague on patients with CVD and DM. Key words: lipids,...
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Evaluation of vegetable fats consumption of patients with cardiovascular disease, diabetes mellitus, dyslipidemia
Kubecová, Markéta ; Vrablík, Michal (advisor) ; Šnejdrlová, Michaela (referee)
The thesis deals with intake of vegetable fats in patients with CVD (Cardiovascular Disease), DM (Diabetes Mellitus) and dyslipidemia. The theoretical part deals with the distribution of lipids, as well as sources ofvarious fatty acids in the diet and their effects on our organism. The next part describes the use of vegetable oils as well as aspects of digestion of fatty acids, their absorption, transport and metabolism. The last chapter of the introduction is dedicated to diseases, in which it is necessary not only to monitor fat intake but, also, choosing those, that can postively impact onthe disease progression. The nutritional (medical) study is made on the basis of a questionnaire survey, which monitors the consumption and use of vegetable fats andfoods containing vegetable fats. Results summarize whether patients are informed and following proper diet regimen and identify mistakes they have been making. Data collection was conducted at the 3rd Department ofInternal Medicine, 1st Faculty of Medicine and General Teaching Hospital in Prague. Keywords: fatty acids, nutrition, metabolism, diet in disease, eating habits
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Pharmacological Influence on Atherogenesis in Experimental Animal Models of Atherosclerosis
Rathouská, Jana ; Nachtigal, Petr (advisor) ; Vrablík, Michal (referee) ; Vohnout, Branislav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Mgr. Jana Rathouská Supervisor: Doc. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Pharmacological influence on atherogenesis in experimental animal models of atherosclerosis Atherosclerosis is a slow inflammatory process in arterial walls which is, as a part of cardiovascular diseases, the main source of morbidity and mortality in developed countries. However, searching for the possibilities of atherosclerosis treatment requires detailed knowledge of pathogenesis of the disease itself. The use of mouse models offers one of the possibilities of studying the pathogenesis of atherosclerosis, which enables a number of interventions that would not be acceptable in human medicine. By using the high content lipid diet, we are able to induce the changes of lipid spectrum in mice. Moreover, if a targeted genetic manipulation is used, one can reach considerably advanced plaques in a relatively short time period. It is also possible to interfere in the process of atherogenesis in mouse models by using some hypolipidemic drugs, for example from the statin group that were represented in our studies by atorvastatin. By observing the vessel's reactivity to atorvastatin dosage,...
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Evaluation and consumption of animal fat in patients with CVD and DM
Opravilová, Jana ; Vrablík, Michal (advisor) ; Horák, Pavel (referee)
The Bachelor thesis deals with the evaluation of consumption of animal fat in patients with CVD and DM. The theoretical part deals with the distribution of lipid, lipid metabolism, the quality of each animal fats, foods containing them and their cooking. The practical part consists of a questionnaire study that tracks the incidence of animal fat and method of preparation in the diet of patients with CVD and DM. Data for this study were taken at III. Internal Medicine, 1st Faculty of Medicine. Keywords Animal fats, nutrition, obesity risks
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Regulation of lipoprotein lipase activity in circulation
Zemánková, Kateřina ; Kovář, Jan (advisor) ; Vrablík, Michal (referee)
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism. The enzyme catalyzes hydrolysis of triacylglycerols (TG) of chylomicrons and of very low density lipoproteins (VLDL). However, the mechanisms involved in the regulation of this protein are not fully understood yet. Therefore, the aim of the theses is to study selected aspects of LPL activity regulation. Recently discovered apolipoprotein A-V (apo A-V) substantially affects triglyceridemia and it is presumed that it may function as LPL activator. However, its concentration in the blood is extremely low and we therefore investigated whether most of apo A-V could be bound to the heparan sulfate proteoglycan (HSPG) of vascular wall similarly to LPL. Intravenous heparin application in healthy volunteers resulted in an expected increase in LPL activity but apo A-V concentration did not change. Our results do not support the hypothesis that most of apo A-V is bound to HSPG of the capillary endothelium. An alcohol consumption plays also a role in LPL regulation - the long-term moderate alcohol consumption is known to increase enzyme activity; on the contrary, it is presumed that LPL activity is inhibited immediately after alcohol consumption. However, the direct evidence for such a premise is missing. The other aim of the theses was to...
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