|
| |
|
| |
|
| |
|
|
The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Polák, Jan (referee) ; Babula, Petr (referee)
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
|
|
|
Adipokines (leptin and adiponectin) as predictors of weight loss and weight regain during one year period following the 10-week low caloric diet (NUGENOB study)
Drahoš, Jan ; Polák, Jan (advisor)
In the Czech republic, about 20% of women and 16% of men are obese. The key role in the etiology of obesity plays the imbalance between energy intake and expenditure, which is influenced by many factors, including leptin and adiponectin. Leptin is secreted mainly from adipocytes and it's levels increase with cell fat content and body fat percentage. Leptin itself is supposed to lead to weight loss, both by decreasing appetite and increasing energy expenditure. But high levels of leptin can be a signal of so called leptin resistance, a state in which leptin is losing it's effects. Adiponectin is secreted exclusively from adipose tissue. In obese people, lower levels of adiponectin were proven (i.e. adiponectin levels are in a negative correlation with body fat percentage). That's consistent with the fact that adiponectin is affecting a range of metabolic prosesses and thus improves insulin sensitivity and metabolic profile. For evaluation, we used a database of almost 750 subjects, that was build under the Nugenob study, conducted in 8 cities in 7 european countries. Al the participants were measured their anthropometric and biochemical parameters at the baseline and after 10 weeks of a standardized weight reduction program. The czech center retested the patient once again 1 year after the initial...
|
|
|
The concept of beauty in Ficino's commentary De amore and its influence on Renaissance aesthetics
Polák, Ján ; Dykast, Roman (advisor) ; Dadejík, Ondřej (referee)
The aim of this study is to examine piece of work of Marsilio Ficino known as De amore according to the characteristic of author's life and work, and to demonstrate its influence on Renaissance aesthetic. The main motive of the writing that was composed as commentary of Plato's Symposion is the function of love in the cosmology inspired by neoplatonists, mainly Plotinus. Ficino's principal contribution to the Renaissance and modern thinking is translation and development of Plato's work including his conception of double love. This study summarizes Ficino's life and work, afterward it examines writing itself emphasizing aesthetic themes and then demonstrates the influence of Ficino's conception of love on selected works of Renaissance literature. The selection of texts exposes transformation of this conception from piece of work directly inspired by Ficino's theory passing through writing in which is this theory confronted with formal literary requirements to the texts demonstrating dominance of literary form over philosophical content. Keywords Marsilio Ficino*Renaissance Platonism*Renaissance aesthetic*platonic love
|
|
|
Role of adipose tissue in the ethiopatogenesis of insulin resistance
Polák, Jan ; Štich, Vladimír (advisor) ; Hainer, Vojtěch (referee) ; Kazdová, Ludmila (referee) ; Rossmeisl, Martin (referee)
Adipose tissue is involved in etiopathogenesis of insulin resistance and subsequent metabolic disorders including type 2 diabetes mellitus and atherosclerosis. Mechanisms responsible for this association are investigated vigorously. One of the well accepted mechanisms linking excessive accummulation of adipose tissue with a development of insulin resistance are free fatty acids, which are released into circulation after hydrolysis of triglycerides stored in adipose tissue in a process of lipolysis. Impairments in a regulation of lipolysis are described in obese patients and lead to increased plasma level of free fatty acids and to impaired mobilisation of energy stores during exercise. In this PhD thesis, regulation of lipolysis in subcutaneous abdominal adipose tissuewas investigated using microdialysis technique. In the first paper we have observed that dysregulation in catecholamine-induced lipolysis and impaired insulin action in adipose tissue can be improved by dynamic-strength training in obese men. In the second study, we have demonstrated significant involvement of newly discovered lipolytic pathway mediated by atrial natriuretic peptide in lipolysis stimulation during exercise. Adipose tissue is producing several protein substances with regulatory and endocrine functions collectively named...
|
|
|
Emerging cardiovascular risk markers in diagnostics and therapy
Tůmová, Eva ; Vrablík, Michal (advisor) ; Freiberger, Tomáš (referee) ; Polák, Jan (referee)
Cardiovascular diseases (CVD) have been one of the leading causes of morbidity and mortality in developed countries with an enormous influence on individual health and significant socioeconomic impact as well. The aim of most physicians in recent decades is to seek the best possible predicative risk factor (RF) (or combination of several RF) which could help to determine the individual risk of developing CVD. This risk stratification can be used to identify the high risk patients and treatment intensification or establishment of early preventive measures. Currently, several RF of atherosclerosis and CVD are commonly used to individualize health care. However, individuals with low levels of these RF suffer of CVD, therefore the effort to find as much as possible specific RF still persists. In recent years, the inflammatory markers, crucial in the atherosclerosis development, raise great expectation In our studies, we focused on investigating the levels of inflammatory parameters in specific groups of patients (obese children and patients with metabolic syndrome) and observed the effect of weight loss following lifestyle changes. Our main concern was lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized LDL particles (ox-LDL) and myeloperoxidase (MPO). The results demonstrated significantly...
|
|
|
Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
|
|
|
Critical limb ischemia and autologous cell therapy in diabetic foot disease, pathogenesis of Charcot osteoarthopathy.
Němcová, Andrea ; Jirkovská, Alexandra (advisor) ; Polák, Jan (referee) ; Prázný, Martin (referee)
Diabetic foot disease (DFD) is a serious complication of diabetes and, along with critical limb ischemia, significantly exacerbates the prognosis of patients. Peripheral arterial disease in patients with diabetes has an atypical clinical course, its diagnosis is challenging and is one of the most common causes of morbidity and mortality of patients with DFD. The aim of this dissertation focused on the diagnosis and treatment of DFD was to identify a suitable method for evaluating the effect of autologous cell therapy (ACT), to assess options for early diagnosis of Charcot osteoarthropathy (COA) and, possibly, to establish the association between the incidence of cardiovascular disease and DFD. In our studies concerning therapeutic vasculogenesis, we observed a significant increase in the antiangiogenic factor endostatin after ACT in contrast to its unchanged levels after standard percutaneous transluminal angioplasty; the transient increase in endostatin seems to be a marker of therapeutic vasculogenesis after ACT. A benefit of using calf muscle perfusion scintigraphy in the assessment of microcirculation and ACT effect was not clearly demonstrated. By contrast, a promising method for the evaluation of microcirculation and the effect of revascularization after ACT was MR spectroscopy of calf...
|
guest ::
