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The role of cold acclimation in ischemicko-reperfusion injury
Marvanová, Aneta ; Žurmanová, Jitka (advisor) ; Čížková, Dana (referee) ; Králová Lesná, Ivana (referee)
Cardiovascular disease, including ischemic heart disease, its acute form of myocardial infarction and subsequent heart failure, is still the most common cause of death in the world. For decades, scientists have been aiming to find clinically usable cardioprotective interventions that effectively prevented this disease or reduced the consequences of this disease and improved the quality of life of patients. It is known that a healthy lifestyle, which includes long-term hardening, contributes to heart protection. The beneficial effects of hardening on personality have been known for two hundred years, but no one before us has investigated the effect of a cold environment on the magnitude of ischemia-reperfusion (I/R) damage 10 years ago, we introduced a model of mild cold exposure (8 ± 1 řC) (MCE) which was protective on the size of the myocardial infarction and at the same time no negative side effects such as hypertension and myocardial hypertrophy were demonstrated. Our aim was to investigate the mechanism of cardioprotection induced by MCE. We asked the following questions: What is the metabolic profile of rats exposed to MCE? What is the effect of MCE on the magnitude of I/R damage in the short and long term? When does brown adipose tissue mature during MCE? Which signalling pathways are...
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Evaluation of the antineoplastic treatment effects on heart electrical activity in experimental telemetric study
Beňková, Daniela ; Janoušek, Oto (referee) ; Ronzhina, Marina (advisor)
This master´s thesis deals with the analysis of experimental telemetrical ECG records with intention to determine the long-term influence of anticancer drug sunitinib on the electrical activity of heart. A laboratory rat was chosen as a model organism for the experimental study carried out at the Department of Physiology at Faculty of Medicine, Masaryk university. The sunitinib was applied to the rats at an early age and the ECG was measured with a 20-week delay using the Stellar telemetry system. To measure the effect of sunitinib on the electrical activity of the heart chambers, an analysis of the duration of the RR and QT interval and the width of the QRS complex was chosen. These parameters were detected by the wavelet transform method. Statistical analysis was performed using nonparametric tests - the Wilcoxon signed rank test, the MannWhitney test and the Friedman Test. The obtained results suggest that the use of sunitinib has no long-term effect on the observed parameters for the chosen animal model. After extension of the study, the results obtained could contribute to assess the effect of drugs on electrical activity of the human heart several decades after sunitinib treatment termination.
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Automatic Processing of DCE-MRI Data
Karela, Jiří ; Mézl, Martin (referee) ; Jiřík, Radovan (advisor)
This master thesis deals with the issue of automatic processing of DCE-MRI data. It describes some important procedures and methods. The work is divided into theoretical part, practical part and conclusion. The theoretical part mainly describes some methods, on the basis of which the practical part was then solved. However, another theory related to the topic is also described here. The practical part then builds on the theory and solves the problem of automatic detection of arterial voxels and the concentration of contrast agent in the arteries. The algorithms are tested on rat brain data obtained from DCE-MRI. The conclusion serves as a summary and evaluation of our results. It also serves as a reflection on the implementation of our methods.
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Segmentation of Cardiac MR Images
Dohnalová, Petra ; Mézl, Martin (referee) ; Jiřík, Radovan (advisor)
This diploma thesis focuses on the influence of myocardial fibrosis on cardiac activity, changes in end-diastolic and end-systolic volume, as well as changes in ejection fraction. The theoretical part is focused on studying the methods used in left ventricular segmentation. The goal is then to implement an algorithm suitable for left ventricular segmentation on the supplied dataset. Based on segmentation, the effect of myocardial fibrosis on the group of rats with induced fibrosis is monitored, at the same time the data are compared with the control group of healthy rats.
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MRI of Rats - Quantification of T1 in Myocardium
Vitouš, Jiří ; Mézl, Martin (referee) ; Jiřík, Radovan (advisor)
This thesis focuses on cardiac imaging and quantification of T1 relaxation time in rat hearts. Its main focus is to investigate available methods for such quantification and their application in the development of quantification tools. The large impact is given to methods of acquisition synchronization, mainly with respect to cardiac motion and breathing using retrospective gating, where the navigator signal is obtained solely from the acquired data, so without any external equipment such as the ECG or respiratory sensors. This paper takes into account situations where steady-state has been reached and also those where it has not, by means of contrast agent injection or by inversion pulses.
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Study of the mechanisms of action of phenolic compounds on vascular smooth muscle
Alves Dias, Patrícia Alexandra ; Mladěnka, Přemysl (advisor) ; Kyselovič, Ján (referee) ; Štengl, Milan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Patrícia Alexandra Alves Dias, M.Sc. Supervisor prof. Přemysl Mladěnka, Pharm.D., Ph.D. Advisor assoc. prof. Jana Pourová, Pharm.D., Ph.D. Title of Doctoral Thesis Study of the mechanisms of action of phenolic compounds on the vascular smooth muscle Cardiovascular diseases including hypertension, coronary artery disease, peripheral artery disease, and cerebrovascular disease remain the leading cause of death worldwide. In addition, discouraging estimations have suggested a future increase in the number of cardiovascular patients. Thus, novel treatment modalities are clearly needed to prevent or reverse these epidemic trends. Phenolic compounds contain one or more hydroxyl groups bound to a benzene ring. This class of chemicals includes: a) natural compounds (e.g., dietary polyphenols and small phenolic metabolites) referred to as nutraceuticals due to their claimed health-promoting effects and b) synthetic compounds (e.g., bisphenols) which, on the contrary, have been suggested to negatively affect human health. Even if there are claims that polyphenol-rich diet is associated with cardioprotective effects, important...
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Cognitive and behavioral alterations in neurodevelopmental and pharmacological animal models of schizophrenia
Malenínská, Kristýna ; Stuchlík, Aleš (advisor) ; Blahna, Karel (referee) ; Telenský, Petr (referee)
Establishing reliable animal models of psychiatric diseases such as schizophrenia is essential to better understand the neurobiological, behavioural and genetic basis of the disorder and to develop new drugs with greater therapeutic efficacy. These models allow the study of different aspects of schizophrenia, including positive, negative and cognitive symptoms similar to schizophrenia. All available animal models of schizophrenia can be divided into four different categories of induction: developmental, pharmacological, genetic and lesion-induced. However, none of these models perfectly replicates all aspects of schizophrenia in humans, and it is therefore necessary to precisely define the influence of each manipulation. This thesis focuses on the study of pharmacological and developmental animal models of schizophrenia, with an emphasis on examining the cognitive and behavioral changes associated with the disorder. Specifically, we investigated the pharmacological induction of schizophrenia- like symptoms by acute administration of MK-801, developmental models of two interventions combining the maternal immune response following poly(I:C) administration and subsequent stress of offspring in adolescence, and repeated prenatal and neonatal administration of lipopolysaccharide (LPS). In the...
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The study of mitochondrial energy-metabolism maturation
Křížová, Jana ; Hansíková, Hana (advisor) ; Pecina, Petr (referee) ; Rauchová, Hana (referee)
During intrauterine development in mammals, the fetus is exposed to a hypoxic environment. To allow proper postnatal adaptation to external conditions, a rapid transition from glycolytic to oxidative metabolism by mitochondria is required in fetal tissues after birth. Mitochondrial maturation is a complex process that is not only transcriptionally regulated. Using techniques such as microarray analysis, quantitative PCR, measurement of enzyme activities or coenzyme Q (CoQ) levels, we have described the acceleration of mitochondrial metabolism in rat liver tissue and skeletal muscle during the perinatal period and correlated the results with those in humans. Of the 1546 rat mitochondrial genes tested, we found statistically significant differences in the expression of 1119 in liver and 827 in muscle. The most significant shift in expression occurred in the rat liver between 20th and 22nd day of gestation, suggesting that the rat fetus is ready for the transition to external conditions at least 2 days before birth. Changes in CoQ levels in both rats and humans show that the amount of CoQ is low inthe prenatal period and increases after birth in both tissues. We have described the atypical kinase Coq8ap as an enzyme whose expression increases significantly after birth. It was previously predicted to...
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Combined pharmacotherapy of different types of pulmonary hypertension
Krása, Kryštof ; Hampl, Václav (advisor) ; Neckář, Jan (referee) ; Al-Hiti, Hikmet (referee)
Pulmonary hypertension is a group of diseases characterized by increased mean pulmonary artery pressure. Especially in group 2, which is associated with heart disease and is the most prevalent of all types, and in group 3, associated with lung disease, no sufficiently effective treatment has yet been developed beyond the treatment of the underlying disease, which is problematic in many cases. Dehydroepiandrosterone sulfate (DHEA S) and statins have different mechanisms of action on pulmonary hypertension in some respects, so the question of the effectiveness of combining them on pulmonary hypertension versus either agent alone has been offered. To test this hypothesis, we induced pulmonary hypertension in adult male rats by three weeks of exposure to hypoxia (10% O2) and treated them with simvastatin (60 mg/L) and DHEA S (100 mg/L) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mean pulmonary artery pressure (from a mean ± s.d. value of 34.4 ± 4.4 to 27.6 ± 5.9 and 26.7 ± 4.8 mmHg, respectively), but their combination was not more effective (26.7 ± 7.9 mmHg). Differences in the degree of oxidative stress (as indicated by malondialdehydedehydplasma concentration), the degree of superoxide production (electron paramagnetic resonance) or blood nitric oxide...
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