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Analysis of bilirubin's relevant photoproducts and their biological significance in the issue of neonatal jaundice
Křepelka, David ; Kozlík, Petr (advisor) ; Zelenka, Jaroslav (referee)
Neonatal jaundice occurs in almost 60% of full-term and 80% of premature babies, where a slightly increased concentration of bilirubin protects against oxidative stress just after birth. When a specific bilirubin level is exceeded in serum (usually above 340 µmol·l-1 ), bilirubin-could induce kernicterus. These negative states are prevented by blue-green light phototherapy (420-510 nm), which converts bilirubin into more polar photoproducts that are more easily excreted via bile and/or urine. Published data have shown that newborns with indicated phototherapy may develop clinical problems later in life (higher incidence of e.g. asthma, allergies, type 1 diabetes was observed at a later age). A possible reason for the occurrence of these diseases is the specific biological activity of photoproducts. This study aims to purify an unknown photoproduct (band P), formed after 8 hours of irradiation of a bilirubin solution with blue light, and to establish a quantitative analytical method for its measurement in relevant matrices. This product was isolated and separated by a thin layer and subsequent column flash chromatography. In the next part, an LC-MS/MS method was developed for quantification of band P. Finally, urine, plasma, and feces samples collected from 15 newborns before and after phototherapy...
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Modeling spatial interactions on the example of the regional cities
Zelenka, Jaroslav ; Marada, Miroslav (advisor) ; Chmelík, Jakub (referee)
Management and planning of transportation is becoming more important in terms of continuously growing intensity of spatial interactions, which are still mostly realized through transport networks. That's why we can deal with this specific problem of transportation geography using for example spatial interactions modeling. The general aim of the thesis is modeling of spatial interactions and their subsequent comparison with real flows by using calibration in order to predicate the future value of flows taking the planned changes in the transport network in consideration. The main tool used to achieve the goal of the thesis is the gravity model which was applied on the example of regional capitals in the Czech Republic. Based on accomplishments we may say, that centers with lower significance of monitored relations are characterized by further location towards most centers, small number of inhabitants, low intensity of model interactions and lower values of transport intensities with neighboring centers. With the center growth itself, its range of interactions with other centers grows as well. Key Words: spatial interactions modeling, gravity model, model interaction, transport intensity, regional capitals
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Struggle for Šwidnica-Jawor duchy under the reign of the Luxembourg dynasty
Zelenka, Jaroslav ; Bobková, Lenka (advisor) ; Vorel, Petr (referee)
Shire of successors of Boleslav I. of Svídnice (Schweidni tz, Swidnica) represents an anomaly in the history of Silesia. Dukes of this branch of Silesian house of Piasts were thoroughly refusing to became vassals of czech king by profi ting of their rel a tionship wi th Wi ttelsbachs, Habsbourgs, Anj ous, as well as wi th polish king Casimir III of Poland. Bolek II of Svidnice was the most powerfull adversary of Luxembourgs. Even by using a military force, John of Luxembourg couldn't break his opposition. Situation had radically changed by the Treaty of Namyslov (Namslau, Namyslów) between Charles IV and Casimir III of Poland in 1348. By this treaty, polish king officially renounced to support his nephew. Charles IV was aware of quali ties of Bolek II and he didn't want to loose him by blessing his ego. So he didn't choose the way of violence, but he gave him a lot of privileges to "buy" his support. Czech king offered to Bolek II the alliance that he couldn't refuse. By this alliance he allowed Bolek to fulfill his power ambi tions what should have never been done, if he had remained adversary of Luxembourg's. Bolek I I of Svidnice was capable to profit from this extraordinary favor until his death. He succeeded to j oin to his shire numerous territories and assure some important economic privileges for...
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Targeted cancer therapy based on altered metabolism of amino acids
Šafrhansová, Lucie ; Starková, Júlia (advisor) ; Zelenka, Jaroslav (referee)
The effects of targeted therapies in the treatment of cancer have been extensively researched and tested in many clinical trials. In contrast to conventional chemotherapy treatment, targeted therapy should act specifically on cancer cells with limited toxicity and lower risk of side effects. One type of targeted therapy exploits the Achilles heel of cancer - the specificity of tumour metabolism. With knowledge of the metabolic differences between tumor and normal cells, we can set up conditions that normal cells easily bridge, while tumor cells die as a result. This can be achieved by removing certain amino acids from the extracellular environment on which cancer cells depend. A well-known enzyme that has been used therapeutically for many years is asparaginase. However, asparaginase therapy is only successful in some cancers, so further development is needed, as well as the search for enzymes with similar effects. Over the years, four other enzymes that could become an integral part of the treatment of cancer patients in the future have been discovered - arginine deiminase, arginase, methioninase and cyst(e)inase. Past and current studies have investigated their effects on cancer cells in vitro and in vivo. Successful elimination of cancer cells often comes with limitations as immunogenicity and...
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The role of oxidative stress in hepatocarcinogenesis.
Kubíčková, Kristýna ; Vítek, Libor (advisor) ; Zelenka, Jaroslav (referee) ; Fraňková, Soňa (referee)
This thesis focuses on the importance of heme catabolic pathway in hepatic carcinogenesis. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumour. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, our study aimed to assess the expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. The study was performed on patients with primary HCC (n = 29) and control subjects (n = 11), gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), endothelial growth factor (VEGFA), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver tissue; the identical gene expressions were analyzed in peripheral blood leukocytes (PBL) in HCC patients (n = 32) and in healthy controls (n = 27). Expression of BLVRA in liver tissue and PBL was significantly increased in cancer patients, as was NOX2 expression in PBL. Expression of VEGFA in liver tissue and PBL was significantly decreased in cancer patients. The expression of the other genes studied did not differ between HCC patients and controls. These data are consistent with the results of our previous study on patients with chronic hepatitis C, in which BLVRA expression was also...
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Mechanisms of regulation of inhibitory factor IF1
Sklenář, Filip ; Dlasková, Andrea (advisor) ; Zelenka, Jaroslav (referee)
Inhibitory factor 1 (IF1) is one of the major regulators of mitochondrial ATP synthase activity, a key enzyme of energy metabolism. Its inhibitory effects are known in conditions such as hypoxia or starvation, but the hypothesis that IF1 inhibits ATP synthase activity even under physiological conditions is still not entirely accepted. Disorders of ATP synthase regulation can be fatal to the cell and have been described, for example, in carcinogenesis and ischemia. It has also been found that silencing of the IF1 gene in pancreatic β-cells increases insulin secretion, and thus, IF1 may be important in the pathogenesis of type 2 diabetes. The goal of this work is to summarize the current knowledge about the IF1 protein and to obtain new results that will help elucidate the mechanism by which this protein regulates mitochondrial ATP synthase. Specifically, this work deals with the ratio of IF1 protein to ATP synthase in pancreatic β-cells, depending on different culture conditions. It further investigates the occurrence of post-translational modifications of the IF1 protein in pancreatic β-cells (INS- 1E model cells), which may play a role in the regulation of IF1 activity. It also deals with the cellular ATP/ADP ratio, which is one of the key factors for insulin secretion by pancreatic β-cells. An...
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The influence of rolfing on the posture and the mobility of the spine
Pavelková, Anna ; Zelenka, Jaroslav (advisor) ; Dušánek, Tomáš (referee)
Bachelor's thesis is categorized as an empirical-theoretical work. Theoretical part is processed in the form of research, and is mainly focused on general characteristics of rolfing. Basic concepts, and their context are explained. Available literature ans articles from web portals Google Scholar, Pubmed, Embase were used in the theoretical part. Studies occupied by the theme of rolfing are included in the first part. Practical part consists of measured data from four probands, photos, description of methods of work, and graphical processing. Evaluating criteria consists of anamnesis (case history), visual inspection, plumage measurement, spinal motion measurement, visual analogue pain scale, emotional evaluation, and motion of fascias. The goal of the thesis is to show positive effects of rolfing. Gained results show a possible positive effect of the method on the human organism.
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The role of cholesterol-7alpha-hydroxylase in cholesterolemia regulation
Procházková, Martina ; Kovář, Jan (advisor) ; Zelenka, Jaroslav (referee)
Cholesterol 7α-hydroxylase (CYP7A1) is an enzyme catalyzing the first step of conversion of cholesterol to bile acids. The enzyme activity is regulated to supply enough bile salts necessary for absorption of fats in the intestine. In some species it contributes to cholesterol elimination from the body when dietary cholesterol intake is high and, in such a way, protects against the development of hypercholesterolemia. CYP7A1 activity can be therapeutically affected by administration of bile acid sequestrants that increase the enzyme activity and thus lower cholesterolemia, and also by administration of bile salts. The enzyme deficiency in humans results in hypercholesterolemia. Several single nucleotide polymorphisms were identified in gene encoding CYP7A1 in humans. They form three large haplotype blocks. The most attention has been paid to the -203A>C polymorphism that has an impact on cholesterol and lipoprotein concentrations, on the response of cholesterolemia to dietary intervention and on the response to hypolipidemic drugs. Key words: Bile acids, cholesterol, cholesterol 7α-hydroxylase, diet, genetics, treatment of hypercholesterolemia
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