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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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Cardioprotective action of remote ischemic perconditioning in rats
Chalupová, Miloslava ; Neckář, Jan (advisor) ; Žaloudíková, Marie (referee)
Remote ischemic perconditioning (RIPerC) stimulated by brief nonlethal periods of ischemia and reperfusion of a remote organ or a tissue applied during myocardial infarction, is a powerful cardioprotective maneuver. Because of its easy realization, for example, through inflation and deflation of blood pressure cuff, this method has a big potential for translation to clinical settings. The main purpose of this thesis was to investigate the cardioprotective effect of RIPerC as a reduction of infarct size and the incidence and severity of ischemic and reperfusion arrhythmias and to examine, whether this protective effect will be confirmed also in rats with partial deletion of a transcriptional factor of hypoxia-inducible factor-1α (HIF-1α). HIF-1α is a main regulator of hypoxic intracellular signalization and its role was previously indicated in cardioprotection by local ischemic preconditioning. Anesthetized rats were subjected to 20 minutes of the left anterior descending coronary artery occlusion followed by 3 hours of reperfusion. RIPerC was performed by 3 cycles of 4 minutes of ischemia and 2 minutes of reperfusion with a pressure cuff placed on both hind-limbs. This study shows that RIPerC failed to induce protection in any observed factors of ischemia-reperfusion heart injury. Key words: heart,...
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Dopad alimentární expozice bisfenolu S na vybrané orgány laboratorních potkanů
ROČEŇOVÁ, Adéla
The present thesis investigated the impact of a ten-week oral exposure to BPS (50 ?g/kg live weight/day) in female outbred Wistar Han rats. The effect of BPS exposure on live weight, absolute and relative kidney and liver weights, morphometric parameters of kidney and renal corpuscles, histopathological changes of kidney and liver were evaluated. In addition, the concentration of total protein, triacylglycerols, cholesterol, urea and alanine aminotransferase activity were determined in blood serum.
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The effect of long-term morphine application on clock genes expression in the rat brain
Pačesová, Dominika ; Bendová, Zdeňka (advisor) ; Roubalová, Lenka (referee) ; Polidarová, Lenka (referee)
The circadian and opioid systems are systems involved in maintaining homeostasis in the body. Disruption of the circadian system disturbs the proper timing of physiological processes, which can result in the development or exacerbation of pre-existing pathological conditions, including addiction. One of the factors that can influence the precise synchronization of the circadian system is the use and abuse of opioids. The interrelationship between the circadian and opioid systems is poorly studied. To this end, the present study investigated the effect of morphine and methadone on the rat circadian system in adulthood and during development. The aim of this dissertation was to observe the effect of acute morphine administration on the expression of clock genes in the suprachiasmatic nuclei (SCN) of adult rats, and to investigate the effect of long-term morphine or methadone administration and withdrawal on the expression of clock genes in the SCN and on the activity of the enzyme AA-NAT in the pineal gland of adult rats. Proper development of the circadian clock contributes significantly to the maintenance of health in adulthood and ensures good adaptability of the organism to changes in the external environment. No study to date has focused on examining the effects of opioid administration during...
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Dopad různé alimentární expozice bisfenolu na játra potkanů
LABUDOVÁ, Kateřina
Bisphenol S (BPS) is an organic compound widely used in industrial production as a substitute for bisphenol A (BPA) for which negative impacts on the human body have been demonstrated and have therefore been significantly regulated. However, as time progresses, the negative properties of BPS are also shown, especially for the endocrine and reproductive systems. The liver is an organ in which xenobiotics are detoxified and thus BPS and BPA. The aim of the bachelor thesis was to verify whether 10-week oral exposure to BPS (4 g, 50 g, 100 mg/kg bw/day) and BPA (100 mg/kg bw/day) will lead to a negative impact on body weight, weight gain, weight and morphological liver structure and on the concentration of triglycerides, cholesterol, total white-vinas, urea and alkaline phosphatase activity in blood serum. The experiment involved 24 rats. BPA and BPS were administered daily by gastric tube in sunflower oil. The results of our research clearly did not show a negative effect of BPS and BPA in rats on body weight, absolute gain, absolute and relative liver weight in rats. There was also no evidence of histopathological changes in rat liver. In contrast, bio-chemical parameters were altered compared to the control group. Decreases in trigly-cerides, total protein content, urea, alkaline phosphatase activity and increases in serum cholesterol were noted. In the 50 g/kg body weight/day group of rats, the highest and lowest decreases in biochemical parameters were observed, respectively. The exposure dose of 100 mg BPS and BPA in our experiment did not cause liver histopathological changes or changes in biochemical parameters according to the hy-pothesis. A possible explanation could be given by the carrier for which sunflower oil with natural antioxidant content was used.
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Účinek bisfenolu S na vybrané krevní parametry potkanů
HLATKÁ, Tereza
Bisphenol S (BPS) is an organic substance which has replaced significantly industrially used bisfenol A (BPA). Eventhough BPS shows higher tolerance against physical influence, there have been registered leaks from the final products and there is a posibility of wather, food and environtment contamination. Until now the BPS has been, just like BPA, mostly connected with disruption of the reproductive system of human and animals. The aim of the bachelor thesis was to determinate whether a ten weeks oral exposure to BPS (50 ?g, 100 mg/kg live weight/day) leads to disturbance in selected haematological parameters (erythrocyte count (RBC), haemoglobin concentration (HGB), haematocrit value (HCT), mean corpuscular volume (MCV), erythrocyte haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), total leucocytes, percentage of granulocytes, lymphocytes and monocytes). Eighteen Wistar Han rats were enrolled in the experiment and they were divided into three groups (control group, 50 ?g BPS, 100 mg BPS). Dissolved BPS in sunflower oil was given to the experimental groupts by a gavage. Blood was collected through cardiac puncture and analyzed using an automated hematology analyser. In the particular study, we found out a nonsignificant decrease of HGB and nonsignificant increase of MCV and MCH in experimental animals. BPS also led to a nonsignificant changes in the number of leukocytes (increase in the total number of leukocytes) and it led to a changes in the number of individual types of the white blood cells representation (increase in the percentage of granulocytes, decrease in lymphocytes). More significant effect was observed in 50 ?g BPS group. Our results did not conclusively proved the negative effect of BPS on the selected blood parameters of rats.
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The effect of morphine withdrawal on G protein-coupled receptors and redox balance in rat brain
Kočárková, Veronika ; Novotný, Jiří (advisor) ; Černá, Barbora (referee)
Although morphine is one of the most effective analgesics available, its long-term use is severely limited by the development of tolerance and dependence. Molecular mechanisms responsible for these effects have been the focus of intensive research for decades aimed at developing safer and more effective pain treatments. The aim of this thesis was to contribute to a better understanding of the molecular actions of morphine, as an understanding of these processes is essential to develop better therapeutic approaches. Using western blot analysis, we investigated the effect of 10-day treatment with increasing doses of morphine and its subsequent withdrawal on key components of opioid signalling in the rat cerebellum and cerebral cortex. Amounts of opioid receptors, various heterotrimeric G protein subunits, GRK3 kinase and β-arrestin 2 were examined. Furthermore, the levels of adenosine A3 receptor and cannabinoid receptor type 1 were detected. Finally, we also investigated the effect of morphine and its withdrawal on oxidative stress markers. Morphine administration resulted in a significant decrease in GRK3 kinase levels in both brain regions, and these changes remained even after withdrawal. However, there was no significant change observed in the content of opioid receptors, different G protein...
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The role of cold acclimation in activation of adrenegic and thyrode signalling pathway in rat myocardium
Tibenská, Veronika
Despite advances in research and therapy, cardiovascular diseases are still the leading cause of death worldwide. A closer understanding of the endogenous protective mechanism may improve pharmacological interventions for the treatment of heart diseases. Cold acclimation or hardening has strong potential for reducing cardiovascular risk and the literature shows that it stimulates the β-adrenergic and thyroid systems in tissues. At the same time, the adrenergic system in the heart is one of the main regulators of cardiac activity. However, these signaling pathways have surprisingly not been studied at the protein level in the heart yet, and no studies can be found on the subject matter in current literature. Our results show a reduced infarct size induced by ischemic injury in cold-acclimated rats (CA) at 8 ř C for 5 weeks and then returning to normothermic conditions for 2 weeks (CAR). The aim of this dissertation is to determine, the degree of involvement of the adrenergic system in the myocardium during acclimation after 3 days, 10 days, 5 weeks of CA and subsequent CAR at the level of all three β-adrenergic receptor isoforms (β-ARs) and their signaling pathways. The results show unchanged signaling of β1-AR-Gs-adenylyl cyclase-protein kinase A in the cardioprotective regimes CA and CAR, whose...
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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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