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Genetic factors of familial hyperlipidemia and prevention of cardiovascular diseases
Todorovová, Veronika ; Češka, Richard (advisor) ; Blaha, Vladimír (referee) ; Karásek, David (referee)
Familial hyperlipidemias are still a current cause of premature development of atherosclerotic cardiovascular disease (ASCVD). Heredity plays an important role in the development of these diseases. Genetic testing helps to specify a definite variant of a given disease and thus the degree of genetic family burden. Together with the clinical examination, it defines the exact diagnosis of the patient and reduces the risk of developing ASCVD in individual specialized care. In the theses, we focused on biochemical and genetic differences and their risk factors for the development of ASCVD in long-term monitored patients with familial hypercholesterolemia (FH), in receptor-mediated FH and familial defect of apolipoprotein B- 100 (FDB). Efficacy, safety, and tolerability of therapy were evaluated in a subgroup of FH patients with PCSK9i therapy. Furthermore, the polygenic genetic risk score (GRS) in patients with the APOE2E2 genotype and its influence on the early detection of the development of familial dysbetalipoproteinemia (FD) were analyzed. Receptor-mediated FH patients carry a mutation in LDLR while FDB patients have a prevalent mutation in APOB. LDL-C and TC levels are high in both groups, although levels are slightly higher in receptor-mediated FH patients. APOE genotype and risk factors such as...
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Fotochemická degradace hypolipidemika atorvastatinu s využitím heterogenní fotokatalýzy.
VONEŠOVÁ, Adéla
The Bachelor s thesis is focused on hypolipidemic drugs statins and their representative atorvastatin. In the theoretical part of the thesis, the function of statins is introduced, studies about statins toxicity for freshwater organisms are presented, fundamentals of heterogeneous photocatalysis are explained and examples of usage of the method for pollutants degradation are given. Experimental part presents kinetics of atorvastatin degradation on TiO2 photocatalyst and a test of toxicity of atorvastatin photoproducts on a water plant (Lemna minor).
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Statiny - jejich použití, mechanismus účinku, vedlejší efekty. Atorvastatin a možnosti jeho fotochemické degradace v přírodních vodách.
PETRÁŇOVÁ, Pavla
The Bachelor´s thesis deals with a group of hypolipidemic drugs, statins. In the theoretical part, their development, characteristics, mechanism of action and side effects are presented. The experimental part is focused on one representant of statins, atorvastatin, its possible photochemical degradation in aqueous solution under light conditions relevant to natural waters, and a potential toxic effect of atorvastatin itself and of the mixture of products of atorvastatin photochemical degradation on a water plant Lemna minor.
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Effect of statin treatment on macrophage polarisation in vitro
Muffová, Barbora ; Kauerová, Soňa (advisor) ; Krulová, Magdaléna (referee)
Statins are widely used for their eminent hypolipidemic effect as anti-atherosclerotic drugs from the 90's of the 20th century. Even though there are new approaches, statins are still the first choice in the prevention of cardiovascular diseases. At the beginning of the 21st century, the anti- inflammatory effect independent of lipid-lowering properties was discovered. This diploma thesis deals with the effect of statin treatment on macrophage polarisation in vitro. Macrophages differentiated from blood monocytes were used in this thesis. The effect of statin treatment on the expression of surface markers (CD16, CD15, CD36, CD163, CD206, ABCA-1 and Trem-2) was evaluated by flow cytometry. The qPCR method was used to quantify the effect of statin treatment on the gene expression of inflammatory genes (NFκB, IL-1β, IL-6, TNFα and iNOS), anti- inflammatory genes (Arg-1, TGFβ) and genes which play a role in the adhesion and migration of monocytes and macrophages to vessel intima (VCAM-1 and MCP-1). Griess method was used to evaluate the effect of statin treatment on the inducible NO-synthase activity. Last, but not least, the effect of statin treatment on proteosynthesis of inflammatory cytokines (IL-1β, IL-6 a TNFα) and anti-inflammatory cytokine IL-10 was measured. Flow cytometry results show that...
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Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
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Ionotropic glutamate receptors and excitotoxicity
Skřenková, Kristýna ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and its excitatory role is mediated trough activation of glutamatergic ionotropic receptors which are responsible for synaptic transmission and play an important role in learning and memory formation. However, excessive exposure to glutamate can result in excitotoxicity which may lead to cell death. The following text is focused on one group of glutamate receptors - NMDA receptors. The study of the receptors is in the centre of current neurobiology research because there is a series of experimental and clinical evidences that they directly participate in the development of serious diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and may cause neuronal damage in trauma, hypoxia and embolia. The aim of this bachelor thesis is to give a brief overview of current knowledge about the structure and function of NMDA receptors and mechanisms of their activation which leads to excitotoxicity and related neuroprotection.
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Evaluation of endoglin and VCAM-1 expression and co-expression in aortas of apoE-deficient mice
Minaříková, Lucie ; Rathouská, Jana (advisor) ; Fikrová, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Evaluatiton of the expresion and co-expresion of endoglin and VCAM-1 in the aorta on apoE- deficient mice Diploma thesis Lucie Minaříková Supervisor: Mgr. Jana Rathouská Background: The aim of this work was to monitor the expression and a possible co-expression of endoglin (TGF-β receptor III) and VCAM-1 in mouse aortic endothelium. As an experimental model, we used the mouse strain C57BL/6J, that was genetically modified, and is characteristic by a deficit of apolipoprotein E. Methodes: In the study, we focused on testing the mouse strain C57BL/6J with gene knockout for apolipoprotein E in different stages of the atherosclerotic process. 10 weeks old female mice were divided into three groups and fed diets with different content of cholesterol. One experimental group was fed a standard diet (called "chow type diet") for a period of two months. The other two groups were fed a diet containing 21% fat (called "Western type diet") for a period of two and four months. For the determination of the levels of total cholesterol, a biochemical analysis of blood was performed. Obtained parts of ascending aorta were analyzed by ImmPRESSTM immunohistochemical method with the detection reagent DAB....
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The coronary atherosclerosis regression during hypolipidemic therapy
Kovárník, Tomáš ; Aschermann, Michael (advisor) ; Rokyta, Richard (referee) ; Pudil, Radek (referee)
Background: There is no study focusing on changes of coronary atherosclerosis during dual hypolipidemic therapy with statin and ezetimibe. Methods: 107 patients with stable angina were enrolled and the final analysis was performed in 89 patients. Randomization was 1:1 to the group A (atorvastatin 80mg and ezetimibe 10mg) and to the standard group S. Treatment period was 12 months. Results: Changes of percent atheroma volume (PAV) were -0,4% in group A and + 1,4% in group S, p=0,014. Combine atherosclerosis regression (increase of lumen volume together with decrease of PAV) was found more frequent in group A (40,5%) than the group S (14,9%), p=0,007. The target LDLc level < 2mmol/l, presence of at least four of five atherosclerotic risk factors, and decrease of VCAM level were independent predictors for plaque regression. There were no significant differences in plaque composition between the two groups over the duration of the study. However during analysis the two groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusion: The dual hypolipidemic therapy starts atherosclerosis regression. Despite significant decrease of lipid levels the continuous plaque shift from fibro and fibro-fatty to necrotic with calcification...
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The importance of biosynthetic and catabolic pathway of cholesterol in inflammatory and tumor diseases
Leníček, Martin ; Vítek, Libor (advisor) ; Haluzík, Martin (referee) ; Mareček, Zdeněk (referee)
This thesis focuses on the importance of intermediate products of biosynthetic and catabolic pathway of cholesterol. The aim of the first part of the thesis is mainly to investigate, whether statins (HMG- CoA reductase inhibitors) possess antitumor properties and to compare the differences in antitumor potential of individual statins. The other part of the thesis aims at the utilization of 7α-hydroxycholest-4-en-3-one (C4), a promising marker of cholesterol 7α-monooxygenase (CYP7A1) activity and bile acid malabsorption. We demonstrated antitumor effect of statins on an experimental model of pancreatic cancer. Individual statins, however, differed significantly in their efficacy, depending on their physico-chemical properties. Our data suggests, that the most likely (but not the only) mechanism of antitumor effect of statins is decreased prenylation of signaling proteins, especially Ras protooncogene. We set up a reliable method for measurement of C4, which facilitated our research in CYP7A1 regulation. We demonstrated, that promoter polymorphism -203A>C might affect CYP7A1 activity, that diurnal variability of CYP7A1 activity might be triggered by insulin, and that insulin resistance in patients with non-alcoholic fatty liver disease impedes the feedback regulation of CYP7A1, which may lead to disease...
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Importance of diet in influencing the risk factors of CVD in patients treated with statins
Bártová, Kateřina ; Vrablík, Michal (advisor) ; Vaclová, Martina (referee)
Diet and other regimens are part of the treatment of dyslipidemia, where the objective is trough modification lipid and lipoprotein metabolism, to influence the cardiovascular risk and to reduce the risk of atherothrombotic compliations. The aim of this work was to investigate the importance of different diets in influencing the risk factors of KVO in patients treated with statins, i.e. to assess the dietary habits of these patients by means of a questionnaire and to monitor the changes, from before to after, of the selected anthropometric and laboratoty parameters. The study included 41 patients of an average age of age of 50 years ± 11. The duration of statin therapy: 88 % of them over half year, 12 % of them less than six months. 73 % of them do not smoke, 27 % were smokers. The dietary habits questionnaire was completed by the patient prior to education and subsequently evaluated. The monitored parameters - weight, waist circumference, blood pressure, total cholesterol, HDL-c, non- HDL-c, LDL-c, triglycerides, glycemia, glycated hemoglobin in diabetics were evaluated before and after 2-3 months of education. Patients were predominantly familiar with the basic rules of a low fat diet but over 30% patients consume food inappropriately for the diet and over 30 % of patients did not consume foods...
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