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The effect of dietary n-3 polyunsaturated fatty acids in the regulation of insulin secretion and glucose homeostasis in mice
Doleželová, Šárka ; Rossmeisl, Martin (advisor) ; Neckář, Jan (referee)
Dietary intake of long-chain polyunsaturated fatty acids of n-3 series (n-3 LC-PUFA), especially eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effect and prevent cardiovascular disease. One of the main targets of n-3 LC-PUFA is adipose tissue, where they activate so called "metabolic switch", resulting in an improvement of lipid and glucose metabolism. In this report, n-3 LC-PUFA suplementation decreased plasma levels of free fatty acids, accumulation of triacylglyceroles in the liver and improved systemic insulin sensitivity in mice fed a high fat diet. There was also a slight decrease in the -cell mass and lower dysfunction of -cells in response to n-3 LC-PUFA feeding. Incretin hormones are secreted from an intestinal cells in response to the ingestion of food, while they also enhance glucose-stimulated insulin secretion. This thesis also analyzed the effect of dietary n-3 LC-PUFA on insulin secretion induced either by the intraperitoneal or oral administration of glucose. The results demonstrated that n-3 LC-PUFA facilitate glucose clearance in response to its oral administration, an effect that is attributable to increased insulin secretion as compared to the effect of intraperitoneal glucose administration. These results suggest that elevated incretin secretion in response...
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The effects of dexrazoxane on ischemia-reperfusion injury in rat heart
Boudíková, Adéla ; Neckář, Jan (advisor) ; Hloušková, Patricie (referee)
Dexrazoxane (DEX) is clinically used to reduce cardiotoxic efects of anthracycline cytostatics. Its cardioprotective efect is caused by chelatation of free iron and defends myocard against dangerous hydroxyl radicals. This research finds out how dexrazoxane works in ischemic-reperfusion damages of rat's heart. Each rat was infused by DEX (50, 150, 450 mg/kg) or by control solution. Isolated perfused rat's hearts were exposed to local ischemia for 30 minutes than 10 minutes of reperfusion for studing ischemic arrhythmias followed by 15 minutes of local ischemia and 10 minutes of reperfusion to examine reperfusion arrhythmias. For evaluation of EKG (ventricular arrhythmias) was used software CAR and Lambeth convention. Global ischemias (15 min.) were induced in rat's hearts (DEX 150 mg/kg) and left ventricules were used for HPLC to determinate concentration of glutathion. In vivo experiments rats were infused by DEX 50, 150 mg/kg or control solution and were exposed for 20 minutes to local ischemia and for 3 hours to reperfusion. Infarct size was evaluated based on the cross section of heart (GIMP, Ellipse). Maximum total number of ischemic arrhytmias decreased by DEX 150 mg/kg (64% comparing to controls). Reperfusion score was reduced by DEX 150 to 48% and percents of ventricular fibrilation was...
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The role of nitric oxide in cardioprotection induced by chronic hypoxia
Mandíková, Petra ; Neckář, Jan (advisor) ; Szárszoi, Ondrej (referee)
The aim of present project was to uncover the effect of pharmacological increase in acute and chronic nitric oxide (NO) production on cardioprotective effect of chronic hypoxia. We studied the effect of NO donor molsidomine on hemodynamic conditions and ischemia - induced myocardium injury. Male Wistar rats were exposed to continual hypoxia in a normobaric chamber (10 % O2, 4 weeks). Rats received molsidomine either chronically (15 mg/kg/day) in drinking water or acutely (10 mg/kg) in saline infused 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to chronic hypoxia resulted in development of pulmonary hypertension. Chronic treatment with molsidomine slightly reduced these consequences of chronic hypoxia but it had no effect on increased cardiac ischemic tolerance in chronically hypoxic rats. On the other hand acute treatment with molsidomine significantly reduced infarct size and increased the number of arrhythmias in both normoxic and chronically hypoxic animals. In conclusion, our data suggests that acute increase in availability of NO is cardioprotective in both normoxic and chronically hypoxic rats contrary to its chronic increase which seems to have no protective contribution.
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The role of the endothelin system in development of hypertension and hypertensive end-organ damage in Ren-2 transgenic rats
Opočenský, Martin ; Červenka, Luděk (advisor) ; Neckář, Jan (referee) ; Widimský, Jiří (referee)
The role of the endothelin system in development of hypertension and hypertensive end- organ damage in Ren-2 transgenic rats Endothelin-I (ET-I) has been described as one ofthe most powerful vasoconstrictors, that also play a role in the regulation of renal hemodynamics. ET system plays an important role in the pathogenesis of salt-sensitive models of hl'pertension. The benefícial effects of ET receptor blockers in modulating target-organ damage arise rrom their antiproliferative action. There is, however, a large discrepancy in the effect of ET between various models of hypertension. The hypertensive rat strain transgenic for the mouse Ren-2 (TGR) renin gene is a valuable monogenetic model of renin-dependent and thus angiotensin lI(Ang ll) - dependent hypertension, which exhibits typical signs of fulminant hypertension,i.e. reduced glomerular fíltration rate and proteinuria associated with g1omerulosderosis. Moreover, it carries a salt- sensitive component. We have recently found that nonselective endothelin ETA/ETB receptor blockade markedly improves survival rate and ameliorates end'-organ damage in malcTGR without lowering blood pressure. Because activation ofthe ETA receptor may be responsible for the detrimental effects of ET in the development of hypertension, our study was performed to...
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Segmentace trhu
Neckař, Jan ; Hebák, Petr (advisor) ; Staněk, Miloš (referee)
Hlavním cílem mé práce bylo užití vícerozměrných statistických analýz v praktickém využití. Vybral jsem si segmentaci trhu. Vytvořil jsem několik skupin lidí, podle toho jaký mají vztah k reklamě. Uživatel této analýzy tak může zaměřit své úsilí pouze na část populace, kde bude reklama účinná.
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