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Pathophysiological mechanisms of chronic kidney disease progression
Sedláková, Lenka ; Kopkan, Libor (advisor) ; Švandová, Ivana (referee)
The kidneys are an essential organ that maintains the homeostasis of body fluid and ions, it filters metabolites and plays important endocrine role. Renal function is controled by many mechanisms with a close interaction that can work independently without central control. These mechanisms are regulated by both systemic and intrarenal humoral systems and their physiological balance sustains the optimal kidney fuction. Any disturbance of this balance leads to the impairments of renal function and progression of renal injury and thus the kidney works inappropriately. The renal insufficiency and diseases remain significant problem despite modern medicine. This is results of several risk factors such as age, genetic predisposition and low birth weight, increase of civilization diseases - diabetes, hypertension, autoimmune disorders, but also bad habits such as unhealthy lifestyle, smoking etc. These factors can lead to the acute or chronic kidney diseases often without known cause. Than the question is an early diagnosis and optimal treatment to preserve kidney function and stop the progression of terminal renal damage. This thesis should show the importance of kidney function and outline problems and consequences of renal insufficiency particularly during chronic kidney disease. Keywords: Renal...
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Physiological and pathophysiological aspects of hydrogen sulfide metabolism in humans
Neminářová, Kristýna ; Kožich, Viktor (advisor) ; Tolde, Ondřej (referee)
Hydrogen sulfide (H2S), known as a toxic gas for a long time, was recently shown to be an important signaling molecule. Hydrogen sulfide is produced in small concentration in organism and exhibits a physiological role in many tissues (brain, blood vessels, lungs). Hydrogen sulfide is mostly formed enzymatically from L-cysteine by two enzymes - cystathionin β-synthase (CBS, EC 4.2.1.22, L- serine hydro-lyase) occurring especially in the brain and cystathionine γ-lyase (CSE, EC 4.4.1.1, L- cystathionine cysteine-lyase) generating hydrogen sulfide mainly in the small intestine, portal vein and thoracic aorta. In vessels hydrogen sulfide acts as a vasorelaxant factor and reduces blood pressure while in the brain it is involved in neuronal transmission. In addition to these effects, hydrogen sulfide plays a role in inflammatory processes as well as in the transmission of pain. Hydrogen sulfide acts through activation of KATP channel (in blood vessels, digestive tract, and in inflammation), activation of NMDA receptors (brain), reduces molecules causing oxidative stress (lungs, brain) and affects influx of Ca2+ ions into the cells (retina). Based on these findings it is apparent that the modulations of metabolism of hydrogen sulfide may have a therapeutic potential, e.g. in vascular disease or in...
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Sleep-dicordered Breathing at Risk Pregnancies
Hudecová, Jana ; Slouka, David (advisor) ; Slípka, Jaroslav (referee) ; Měchurová, Alena (referee)
The aim of this thesis is to highlight the severity of sleep-disordered breathing at risk pregnancies, as these disorders have a high share on the occurrence of cardiovascular problems at a later age. In the group of high-risk pregnant patients, breathing disorders in sleep lead to higher morbidity of patient as well as newborns. Currently, there are increasing risk factors in the population of pregnant women. Risk factors for the development of OSAS, which are examined in detail in this thesis in pregnant women, include BMI, age, pregestational and gestational hypertension and diabetes mellitus. The theoretical part of the thesis contains the findings of the risk pregnancies. The most serious unit is preeclampsia. For that reason, the greatest attention within high- risk pregnancies is aimed to the incidency, ethiopathogenesis, diagnosis and treatment of preeclampsia. Furthermore, the theoretical part includes findings related to sleep- disordered breathing and focuses on OSAS and its health complications. In the special part of the thesis, there is an assessment of results regarding risk pregnant women with the presence of OSAS and without present OSAS. Keywords Preeclampsia, hypertension, OSAS, pregnancy, risk factors
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Novel Approaches To Protect The Heart Against Postischemic Failure
Hrdlička, Jaroslav ; Papoušek, František (advisor) ; Zicha, Josef (referee) ; Vízek, Martin (referee)
Ischemic heart disease and resulting heart failure (HF) belong to the leading causes of death in developed countries. In order to prevent HF and improve clinical outcome in patients with myocardial infarction, novel therapies are required to protect the heart against the detrimental effect of ischemic injury. Due to the failure to translate numerous available experimental cardioprotective strategies into clinical practice, the need for novel protective treatments persists. We have, therefore, tried to apply a novel approach to cardiac protection against the postischemic HF induced in rats by ligation of the coronary artery. For this purpose, we have studied (i) the preventive and therapeutic effects of adaptation to continuous normobaric hypoxia (CNH; 12% O2) and exercise training (ExT; treadmill running), and (ii) the possible cardioprotective potential of epoxyeicosatrienoic acid (EET)-based therapy in order to attenuate the postischemic HF in rats. Adaptation to CNH and ExT is known for their cardioprotection in acute ischemia/reperfusion (I/R) injury manifested as reduction of infarct size. EETs exert antihypertensive effects and thus seem to be perspective for the research in clinically relevant models of cardioprotection in hypertensive animals. Our results have revealed that: - CNH prior to...
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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...
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Applications of chiral and achiral chromatography in pharmacology and toxicology
Chytil, Lukáš ; Slanař, Ondřej (advisor) ; Bultas, Jan (referee) ; Coufal, Pavel (referee)
Development and validation of methods for analysis of several drugs or their metabolites are decribed in this thesis. The document is presented as a commentary to the original papers, which were published in peer reviewed journals. Discussion on the optimization of each method is presented and covers also method development and influence of preanalytical aspects. Additionally, examples of the application of the developed methods in clinical pharmacology and toxicology are shown. This dissertation consists of three parts: enantiomeric determination of tramadol and its metabolite, determination of some antihypertensive drugs, and qualitative analysis of benzodiazepines. Development of a method for chiral analysis of tramadol and its desmethylated metabolite O- desmethyltramadol (ODT) in human urine and plasma is described in the first part of the thesis. Tramadol is a centrally acting analgetic drug, which is used as racemate in clinical practise. Each enantiomer displays different binding properties for various receptors: (+)-tramadol preferentially inhibits serotonin reuptake while (-)-tramadol mainly inhibits noradrenalin reuptake. (+)-tramadol is considered 10-times more potent than (-)-tramadol. Major active metabolite (ODT), which is considered to be the main agent responsible for the...
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Left ventricle remodeling in patients with primary aldosteronism and essential hypertension
Indra, Tomáš ; Holaj, Robert (advisor) ; Ošťádal, Petr (referee) ; Paleček, Tomáš (referee)
Myocardial damage is one of the most serious consequences of arterial hypertension. Changes in the heart structure and function develop not only due to pressure overload itself, but many other hemodynamic and neurohumoral factors contribute to their formation. Our work has compared echocardiohraphic strucutural anf functional changes of the left ventricle, caused by essential hypertension and hypertension associated with primary aldosteronism (PA) as the most common reason for secondary hypertension. The first part of our work focused on the differences in left ventricle geometry in men with PA and essential hypertension after separating it's low-renin form (where, similarly to PA, the plasma volume expansion was considered to have the dominant effect on left ventricle remodelation). In men with low-renin forms of hypertension including PA, we observed greater both endsystolic and enddiastolic diameter of the left ventricle, lower relative wall thickness and more frequent eccentric type of hypertrophy when compared to essential hypertensives with normal renin levels. Whereas left ventricle cavity diameters were positively correlated to aldosterone levels, wall thicknesses were associated mainly with hypertension severity expressed as an average 24hour blood pressure and number of antihypertensives....
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Neural mechanisms in the pathogenesis of spontaneous hypertension in the rat
Vavřínová, Anna ; Zicha, Josef (advisor) ; Haluzík, Martin (referee) ; Neckář, Jan (referee)
Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...
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Causal interaction analysis of cardiovascular signals
Tiurina, Mariia ; Kolářová, Jana (referee) ; Svačinová, Jana (advisor)
Application of the non-invasive methods to detection of the baroreflex sensitivity is a correct way to evaluate the functions of cardiovascular system. This master’s thesis describes the theoretical informations about the problem of baroreflex sensitivity from anatomical, patalogical and clinical views. Theoretical knowledges are foundation for mathematical description of some methods to detection of baroreflx sensitivity in time, frequency and information dimensions. In the practical part of the master’s theses are presented two methods of BRS detection – sequence method based on finding the specific sequences of time series signals and method of application bivariante autoregressive model. Both of methods are implemented in MATLAB. The results of testing data on real data are discussed.
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