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The role of mixed function oxidases system with cytochrome P450 in metabolism of drugs and carcinogens
Mrízová, Iveta ; Stiborová, Marie (advisor) ; Levová, Kateřina (referee) ; Hansíková, Hana (referee)
6 Abstract Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an alkaloid isolated from Apocynaceae plants, exhibits significant antitumor and HIV activity. This antitumor agent binds to DNA and forms covalent DNA adducts. Enzymes, which are involved in its enzymatic activation, are cytochromes P450 (CYP) and peroxidases. To elucidate the effect of ellipticine on the expression and enzymatic activity of the individual components of the microsomal mixed function oxidase system in different tissues, we used rat model. Simultaneously, the effect of ellipticine and its cytotoxicity on different tumor cell lines was also investigated. Another part of the presented work was targeted on preparation of anti-peptide antibody against orphan cytochrome P450 2S1, which is highly expressed in many human tumours of the epithelial origin, for its detection in these tissues. For better understanding how CYP2S1 can contribute to the metabolism of xenobiotics, the protein was prepared by heterologous expression in E. coli. Furher, its role in metabolism of an antitumor drug ellipticine, a carcinogenic environmental pollutant benzo[a]pyrene (BaP) and its derivate BaP-7,8-dihydrodiol was examined. Utilizing a mouse model, the impact of pulmonary inflammation on the metabolism of an environmental carcinogen was...
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Interaction of food additives with xenobiotic metabolising enzymes
Jandová, Eliška ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Recently the use of various food supplements as a part of a healthy lifestyle has been very popular. Although most of them are natural products, their excessive consumption may not always be beneficial for health. Dietary supplements are usually of a flavonoid character. Flavonoid compounds are found in plants and they have beneficial effects on human health. For their antioxidant, anti-allergy and chemopreventive effects they are extensively studied. However, in recent years the negative impacts of flavonoids have been described, often caused by their excessive consumption. It has been shown that they interact with cytochrome P450, which play an important role in the biotransformation of xenobiotics. The change in the metabolism of xenobiotics (whether drugs or carcinogens) can cause serious health problems, including a tumor growth. Beside cytochrome P450, there is another possible points of intervention, cytochrome b5 (or NADH:cytochrome b5 reductase), which effects the catalytic cycle of cytochrome P450. Another point of potential danger is the elimination of xenobiotics out of the organism. There is a complex system of transporters, in which P-glycoprotein plays a very significant role. P-glycoprotein is involved in transmembrane efflux of xenobiotics, preventing the aggregation of these...
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Wood ants of genus Formica as important ecosystem engeneers
Jílková, Veronika ; Frouz, Jan (advisor) ; Tajovský, Karel (referee) ; Bonkowski, Michael (referee)
This thesis consists of one chapter accepted for publication in a book and four papers published in international journals with impact factors. All of the contributions deal with the role of wood ants in energy and nutrient fluxes in forest ecosystems. Wood ant nests are known as hot spots of carbon dioxide (CO2) production and are also thought to affect methane (CH4) flux. Stable high temperatures are maintained in ant nests even in cold environments. This study is focused on quantification of CO2 and CH4 flux in wood ant nests, contribution of ants and microbes to CO2 production, properties of nest material that affect CO2 production and the role of ants and microbes in the maintenance of nest temperature. The research was conducted in temperate and boreal forests inhabited by wood ants (Formica s. str.). Gas fluxes were measured either by an infrared gas analyser or a static chamber technique. Ants and nest materials were also incubated in a laboratory. Material properties potentially influencing CO2 flux, such as moisture, nutrient content or temperature were determined. According to the results, CH4 oxidation was lower in wood ant nests than in the surrounding forest soil suggesting that some characteristics of ant nests hinder CH4 oxidation or promote CH4 production. Wood ant nests clearly are hot...
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Calcium intake in the diet of VFN medical staff
Figalová, Sandra ; Raška, Ivan (advisor) ; Michalská, Dana (referee)
This thesis deals with calcium as one of the most important micronutrients in our body. The theoretical part describes the basic functions of calcium in the human body and its metabolism. Further it concerns significant resources of calcium and diseases associated with its excess or deficiency. The theoretical part also deals with calcium homeostasis and the factors affecting it and recommended daily calcium intake for different age groups. The practical part of this thesis includes quantitative research of calcium intake in the diet of medical staff at the General University Hospital in Prague reviewed through included graphs. It concerns mainly the calcium intake in the diet of nurses of the 3rd Internal Clinic of General University Hospital in Prague. The observed dietary calcium intake among nurses is sufficient for 50% of them. The second half of the respondents, however, evidence the lack of micronutrients in their diet. The results found were compared then to the recommended daily allowances of calcium. The practical part also evaluated the overall awareness of nurses about calcium intake and the incidence of calcium in the diet which is unsatisfactory for most of them. Finally, besides the detailed results, this thesis presents recommendations that could lead to improvement of the above conclusions...
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Biogenesis of mitochondria in parasitic protist Trypanosoma brucei
Mach, Jan ; Tachezy, Jan (advisor) ; Yurchenko, Vyacheslav (referee) ; Hashimi, Hassan (referee)
In last decade, investigations of mitochondria including their various reduced forms such as hydrogenosomes and mitosomes revealed unexpected diversity of this indispensable organelle. Interestingly, the single mitochondrion of parasitic protist Trypanosoma brucei is able to undergo remarkable functional and structural changes reflecting available carbon sources. Moreover, it was proposed that trypanosomes belong among the most ancient eukaryotes and as such, their mitochondria raised high attention of biologists. To contribute to the knowledge of mitochondrial biogenesis and function, we focused on studies of two key mitochondrial processes, the processing of preproteins that are imported to the mitochondria, and mechanism of pyruvate transport to these organelles. Moreover, we also investigated uptake of iron by T. brucei. This metal is essential for function of numerous proteins, particularly for iron-sulfur proteins in mitochondria. Evolutionary history of trypanosomes and their mitochondrion is a question of debates. According to some reports, mitochondrion of trypanosomes represent an ancient form of this organelle, which is supported by identification of putative "archaic" translocase of the outer mitochondrial membrane (ATOM) and finding of only a single type of translocation pore in...
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Measurement of liver metabolic profile using MR spectroscopy
Vratislavská, Hana ; Wagnerová, Dita (advisor) ; Šoltésová, Mária (referee)
This bachelor thesis deals with application of MR spectroscopy for determination of metabolite signal intensities and chemical changes in human liver. Measurements were performed in a magnetic field with induction 3T using proton and dual proton/phosphorus surface coils. First we did experiments with three chemical solutions. Then we measured MR spectrums of 28 healthy volunteers who were divided into four groups by gender and body mass index (BMI). During measurements with phantoms we found out dual coil range and inappropriateness of adiabatic pulses usage. Also we realized that it would be necessary to use buffer solutions. During measurements with healthy volunteers we found out that it is necessary to narmalize signal intensities by water or total phosphate, however, it would not be necessary to use correction factors for groups comparison with different sex and BMI.
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Factors influencing weight gain in pregnncy
Vodrážková, Nicole ; Kaňková, Šárka (advisor) ; Horníková, Daniela (referee)
In this bachelor thesis I described different factors influencing weight gain in each trimester of pregnancy. There are factors influenced by a lifestyle, such as diet, physical activity, smoking, and BMI before pregnancy. There are also factors which are given individual dispositions, changes in metabolism and hormonal status of the organism. On this basis, this thesis deals with the consequences, that has excessive or insufficient weight gain in pregnancy for the mother and her fetus.
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Evaluation of animal fat consumption of patients with cardiovascular disease, diabetes mellitus
Šťovíčková, Jana ; Vrablík, Michal (advisor) ; Šnejdrlová, Michaela (referee)
This bachelor's thesis is focused on animal fat consumption of patients with cardiovascular disease (CVD) and diabetes mellitus (DM). Content of thesis is divided into theoretical and practical part. The main objective of theoretical part is to provide a general description of lipids in terms of distribution, structure, characteristics and their role in human organism. In the following chapters metabolism and transport of lipids is described with more attention to details. The last part of theoretical part deals with animal fats in nutrition, mostly risk factors as a consequence of their increased consumption, and dietary measures as a prevention and therapy of CVD and DM. The practical part of bachelor's thesis is based on assessment survey. The object of this survey was the evaluation of eating habits, mainly the measure of animal fats consumption of patients with CVD and DM. Next object of interest was the evaluation of awareness, knowledge and education these patients have about dietary measures in relation to their disease. Question about the way how are these measures followed by patients was also examined. The survey was conducted in the diabetological center and also in the centre of preventive cardiology of General Teaching Hospital in Prague on patients with CVD and DM. Key words: lipids,...
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