|
|
Pyrazine derivates as potential drugs I.
Klusoňová, Petra ; Doležal, Martin (advisor) ; Opletalová, Veronika (referee)
Title of diploma thesis: Pyrazine derivatives as potential drugs I. Review of actual worldwide problem of tuberculosis and trends in the tuberculosis treatment and chemical recherché were the parts of this work. Novel pyrazine derivatives connected via -CONH- bridge with substituted anilines were synthesized. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of twelve newly synthesized compounds were presented. All products were characterized and tested against Mycobacterium tuberculosis strain H37Rv and against eight fungal pathogen strains. Additionally, the study of inhibition of oxygen evolution rate in spinach chloroplasts and reduction of chlorophyll content in the green algae Chlorella vulgaris in the series of prepared compounds were drawn. Structure-activity relationships among the chemical structure, lipophilicity (log P), and their biological activity of the evaluated compounds were discussed as well.
|
|
|
Molecular mechanisms of insulin sensitivity in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Klusoňová, Petra (referee)
Insulin resistance is a key component of the pathogenesis of metabolic syndrome and type 2 diabetes. Skeletal muscle is an important part of energy metabolism. It recieves, stores and uses most of the glucose from blood. Insulin stimulates glucose uptake, by promoting translocation of glucose transpoters to plasma membrane. It also increases the rate of protein, glycogen and triglyceride synthesis. When muscle is unable to respond to normal levels of circulating insulin, insulin resistance occurs. Insulin resistance leads to disruption of key metabolic processes. Fatty acid transport across the membrane is upregulated, whereas the ability to oxidize fatty acids is decreased. This imbalance leads to accumulation of lipid metabolites inside the cells. Lipid intermediates may interfere with insulin signalling. Inflammatory cytokines, particularly TNF, activate kinases that may inhibit the insulin signal transmission. Insulin resistance may be treated pharmacologically, but also physical activity and decrease of energy intake are important part of therapy. Also polyunsaturated fatty acids have beneficial effects on muscle insulin sensitivity.
|
|
|
Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
|
|
|
Molecular mechanisms of insulin sensitivity in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Klusoňová, Petra (referee)
Insulin resistance is a key component of the pathogenesis of metabolic syndrome and type 2 diabetes. Skeletal muscle is an important part of energy metabolism. It recieves, stores and uses most of the glucose from blood. Insulin stimulates glucose uptake, by promoting translocation of glucose transpoters to plasma membrane. It also increases the rate of protein, glycogen and triglyceride synthesis. When muscle is unable to respond to normal levels of circulating insulin, insulin resistance occurs. Insulin resistance leads to disruption of key metabolic processes. Fatty acid transport across the membrane is upregulated, whereas the ability to oxidize fatty acids is decreased. This imbalance leads to accumulation of lipid metabolites inside the cells. Lipid intermediates may interfere with insulin signalling. Inflammatory cytokines, particularly TNF, activate kinases that may inhibit the insulin signal transmission. Insulin resistance may be treated pharmacologically, but also physical activity and decrease of energy intake are important part of therapy. Also polyunsaturated fatty acids have beneficial effects on muscle insulin sensitivity.
|
|
|
Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
|
|
|
Pyrazine derivates as potential drugs I.
Klusoňová, Petra ; Doležal, Martin (advisor) ; Opletalová, Veronika (referee)
Title of diploma thesis: Pyrazine derivatives as potential drugs I. Review of actual worldwide problem of tuberculosis and trends in the tuberculosis treatment and chemical recherché were the parts of this work. Novel pyrazine derivatives connected via -CONH- bridge with substituted anilines were synthesized. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of twelve newly synthesized compounds were presented. All products were characterized and tested against Mycobacterium tuberculosis strain H37Rv and against eight fungal pathogen strains. Additionally, the study of inhibition of oxygen evolution rate in spinach chloroplasts and reduction of chlorophyll content in the green algae Chlorella vulgaris in the series of prepared compounds were drawn. Structure-activity relationships among the chemical structure, lipophilicity (log P), and their biological activity of the evaluated compounds were discussed as well.
|
|
|
Analysis of the importance of LPG as an alternative fuel for the vehicular transport in the Czech Republic
Klusoňová, Petra ; Dvořák, Antonín (advisor) ; Hadrabová, Alena (referee)
The main goal of this economic paper is to analyse the importance of LPG as an alternative fuel for the vehicular transport in the Czech Republic and to simplify the decision of potential applicants about the conversion of a car engine to run on LPG. At first this text briefly describes the main kinds of alternative fuels. Then the text focuses on LPG itself that is defined and described including its application in the past and at present. The next section of this paper is concentrated on the individual decision about the conversion of his car engine to run on LPG and the main attention will be focused on the environmental, economic, technical and institutional aspects of this conversion. Then the text compares LPG and CNG because CNG could be considered to be the main competitor of LPG in the field of alternative fuels. At the conclusion the paper summarizes the discovered facts and tries to predict future use of LPG as an alternative fuel in the Czech Republic.
|
|
|
Euro adoption and evaluation of its (lack of) success so far on the example of Germany
Klusoňová, Petra ; Hlaváč, Petr (advisor) ; Heřmanský, Pavel (referee)
Tato práce stručně charakterizuje hlavní události, které vedly ke vzniku eura jako společné měny. Dále uvede základní očekávané náklady a výnosy plynoucí ze zavedení eura. V další části této práce bude provedena komparace vývoje vybraných ekonomických ukazatelů před zavedením eura a po jeho zavedení na příkladu Německa jako jednoho z nejvýznamnějších, největších a nejlidnatějších členských států EU. Veškeré tyto komparace budou prováděny z důvodu konfrontace jejich výsledků s teoretickými předpoklady o výnosech, které byly očekávány při vstupu do EMU. Na závěr tato práce shrne zjištěné skutečnosti a zhodnotí vliv přijetí eura na vývoj některých ekonomických ukazatelů ve sledované oblasti.
|
guest ::
