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Interaction of selected flavonoids with cytochromes P450 2B
Boštíková, Zdislava ; Hodek, Petr (advisor) ; Kubíčková, Božena (referee)
In recent years, there has been increased emphasis on healthy lifestyle, which includes, among others, consumption of natural nutrients in a form of various food supplements. These compounds, usually of a flavonoid character, show different chemopreventive effects such as anti-oxidant or anti-carcinogenic. The excessive consumption of these compounds can also have a negative impact on human health. Flavonoids may for instance influence the content of biotransformation enzymes, cytochromes P450, in the cells and thus influence the metabolism of foreign compounds. Such an influence might, as a result, lead to a development of carcinogenesis or inefficacy of certain medications. The main focus of this bachelor thesis is to study capabilities of two flavonoid compounds (myricetin and dihydromyricetin) to induce and inhibit cytochromes P450 of 2B family. By the Western blot method it was found that neither of the investigated flavonoids increased expression of CYP2B1/2 in livers, myricetin, or in any part of small intestine. In the case of dihydromyricetin there was noticed an induction of cytochromes P450 2B in the middle part of small intestine. The inhibitory potency of flavonoids was examined in vitro as an inhibition of 7-pentoxyresorufin O-depentylation catalyzed by CYP2B. Values of IC50 8,8μM and...
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Changes of Immune Parameters Induced by Intraamnial Inflammation
Souček, Ondřej ; Andrýs, Ctirad (advisor) ; Lokaj, Jindřich (referee) ; Šimetka, Ondřej (referee)
Changes of immune parameters induced by intraamnial inflammation Abstract Intraamniotic infection plays an important role in the etiology of preterm birth and can lead to a serious threat to fetal health. The diagnostic approach is based on direct microbiological detection of an infectious agent or indirect detection by determining various biomarkers, which concentration increases during intraamniotic infection. Due to the nature of the infection, these parameters are determined from amniotic fluid, which makes this diagnosis difficult for both the doctor and the mother and routinely unavailable. The dissertation comments the published results of a scientific team whose aim was to identify suitable markers of infection, determine their concentration in amniotic fluid and test their diagnostic potential in cervical fluid, ie biological material that can be collected non- invasively. Amniotic and cervical fluid samples were taken from women with singleton pregnancies with preterm labor and that were complicated by intraamniotic inflammation and infection in part of the cohort. It was found that among the tested molecules there is a statistically higher concentration of calreticulin, cathepsin G, CD11b, FcgammaBP and MIP1α in amniotic fluid during intraamniotic infection. Significantly higher levels of...
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The effect of dihydromyricetin and myricetin on selected biotransformation enzymes
Boštíková, Zdislava
Flavonoids are natural compounds commonly ingested in herbs and vegetables. They are believed to have a positive impact on human organism, in particular by their antioxidant, hepatoprotective and anti-cancer effects. In these days, it is possible to consume high concentrations of these compounds in form of dietary supplements. However it is not clear, whether flavonoids in such unnaturally high concentrations are still beneficial or rather harmful. It has already been proven, that flavonoids can influence the activity of biotransformation enzymes and interfere e.g. with the process of carcinogenesis and drug metabolism. For that reason it is important to investigate the impact of an increased intake of flavonoids. The aim of this thesis was to investigate the influence of dihydromyricetin (a potential drug to cure alcohol use disorder) and its structurally similar flavonoid myricetin on the activity of enzymes, cytochrome P450 2E1 (CYP2E1) and Nacetyltransferases 1 and 2 (NAT1/2). The research included the determination of the impact of a premedication by these flavonoids on the expression and activity of CYP2E1 and NAT1/2. The inhibition capacity of myricetin and dihydromyricetin towards the activity of CYP2E1 and NAT1/2 was also investigated. After the flavonoid premedication of rats the...
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Study of the effect of roscovitine and its derivatives on the expression of drugs transporters in vitro
Mlčochová, Alice ; Čečková, Martina (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Mgr. Alice Mlčochová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of rigorous thesis: Study of the effect of roscovitine and its derivatives on the expression of drugs transporters in vitro In this study we aimed to evaluate interactions of selected inhibitors of cyclin-dependent kinases (CDKi) with efflux transporters ABCB1 (P-glycoprotein, P-gp, MDR1) and ABCG2 (breast cancer resistance protein, BCRP) in cell line LS174T derived from human adenocarcinoma of colon. Among the selected compounds belong roskovitin and its derivates designed as BA-12 and BP-14. Previous studies demonstrated that these substances inhibit both mentioned transporters and therefore increase the effect of simultaneously administrated cytotoxic drugs. Since the drug interactions on the level of transporters can arise from induction of their corresponding genes, the aim of this work was to extend the current knowledge on mentioned derivates of roskovitin in terms of possible affection of ABCB1 and ABCG2 expression. Enhanced expression could promote developement of multidrug resistance (MDR). Results of this work obtained with qRT- PCR method show that neither BA-12 nor BP-14 increase expression of...
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Electronic RLC meter
Dvořák, Radim ; Hanák, Pavel (referee) ; Lattenberg, Ivo (advisor)
This work deals with measurement methods of passive components R, L ,C used almost in every electrical circuit. Work describes progress of choosing the right methods for measurement and also the process of designing the autonomous RLC meter with use of ATMEL microprocessor chips. The RLC meter will be powered from rechargable battery and will be able to measure primary attributes of RLC components.
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Drop-out of the beginning teachers
Krejčová, Martina ; Zvírotský, Michal (advisor) ; Thorovská, Alena (referee)
The Diploma thesis focuses on the drop-out of beginning teachers. Theoretical part elaborates on the phenomenon of drop-out, it describes the reasons why the beginning teachers leave and why they are the group of teachers which is the most threatened by drop-out. Furthermore, this part describes problems that beginning teachers have to deal with and the most frequent reasons for leaving the profession, their rate and consequences of drop-out. The end of the theoretical part presents options and suggestions that would help solve this problem. The empirical part of the thesis is realized by an on-line questionnaire and in-depth interviews. The research focuses on four main aspects: 1 - the motivation to study the teaching and to practise it, 2 - the main reasons for new teachers to leave, 3 - the possibilities to prevent drop-out and 4 - whether the respondents continue to work with children or not. Last but not least, the research focuses on the possibilities that would help respondents to stay in the profession. The results of the research confirm the reasons for quiting as described by literature. The qualitative description of the reasons for drop-outs provides a deeper understanding of how they interact in an institutional, interactive and cultural level. KEYWORDS Induction period, teacher...
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The effects of endocrine disruptors on the expression and the activity of cytochromes P450 2B in laboratory rat as a model organism
Měkotová, Barbora ; Dračínská, Helena (advisor) ; Levová, Kateřina (referee)
Endocrine disrupting chemicals are compounds that interfere with natural hormones and they are responsible for functional changes which may lead to damage of the endocrine system. Their presence in the environment is associated with a number of diseases whose extent is hard to predict. As endocrine disrupting chemicals, a wide range of exogenous and endogenous compounds is present in the environment. Important exogenous endocrine disrupting chemicals include benzo[a]pyrene (BaP) and 17α-ethinylestradiol (EE2); the female sex hormone 17β-estradiol (E2) can act like endogenous endocrine disruptor. In this thesis, the effect of these three compounds and their combinations on the expression and the activity of rat biotransformation enzymes cytochromes P450 2B is studied. The gene expression was determined by quantitative PCR, the expression of the protein itself was studied using Western blot method and consecutive immunodetection. The results show that CYP2B expression is almost unchanged after BaP premedication, whereas estrogenic compounds, E2, EE2, their combination and their combinations with BaP, significantly decrease the expression. The enzyme activity of CYP2B was also studied in rat liver microsomes using the marker substrate 7-pentoxyresorufin. EE2, E2 and their combination decrease the...
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The effect of dihydromyricetin and myricetin on selected biotransformation enzymes
Boštíková, Zdislava
Flavonoids are natural compounds commonly ingested in herbs and vegetables. They are believed to have a positive impact on human organism, in particular by their antioxidant, hepatoprotective and anti-cancer effects. In these days, it is possible to consume high concentrations of these compounds in form of dietary supplements. However it is not clear, whether flavonoids in such unnaturally high concentrations are still beneficial or rather harmful. It has already been proven, that flavonoids can influence the activity of biotransformation enzymes and interfere e.g. with the process of carcinogenesis and drug metabolism. For that reason it is important to investigate the impact of an increased intake of flavonoids. The aim of this thesis was to investigate the influence of dihydromyricetin (a potential drug to cure alcohol use disorder) and its structurally similar flavonoid myricetin on the activity of enzymes, cytochrome P450 2E1 (CYP2E1) and Nacetyltransferases 1 and 2 (NAT1/2). The research included the determination of the impact of a premedication by these flavonoids on the expression and activity of CYP2E1 and NAT1/2. The inhibition capacity of myricetin and dihydromyricetin towards the activity of CYP2E1 and NAT1/2 was also investigated. After the flavonoid premedication of rats the...
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Study of selected flavonoids as modulators of cytochrome P450 3A4
Skotnicová, Aneta ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Flavonoids are secondary metabolites of plants exhibiting a wide range of biological activities. Special attention is paid to them mainly because of their antioxidant properties. Consumption of these natural substances is currently increasing especially in the form of dietary supplements. In addition, these compounds exhibit antiviral, anti-inflammatory or hepatoprotective effects and some of them also exhibit mutagenic and/or pro-oxidative properties. The study of flavonoid interactions with biotransformation enzymes such as cytochromes P450 are important because of their possible interference with the metabolism of drugs or carcinogenesis processes. In this bachelor thesis the influence of selected flavonoid compounds, dihydromyricetin and myricetin, on the expression and activity of cytochrome P450 3A4 was studied. The flavonoid premedication of rats did not resulted in induction of CYP3A4. However, dihydromyricetin and myricetin inhibit CYP3A4. IC50 were determined as 25 M for dihydromyricetin and 24 M for myricetin. Key words: Immunodetection, HPLC, inhibition, induction (In Czech)
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The Detective Who Misled in His Own Method
Knorková, Marie ; Švantner, Martin (advisor) ; Karľa, Michal (referee)
In this thesis I analyze detective Sherlock Holmes method based on the semiotics of Ch. S. Peirce. I would like to show that although Holmes detective about his method claim that it is deductive, in-depth analysis shows that this method is far more complex and involves induction and abduction, and that each of these methods has its own importance in the detective's reasoning. The work is divided into three parts. The first part focuses on the Sherlock Holmes detective in terms of logical methods. The second part is focused on methods of reasoning by Ch. S. Peirce emphasizing abduction, a hypothesis. The third part is practical and includes analysis of the process of detective Sherlock Holmes based on the thesis of Ch. S. Peirce, as outlined in the second part.`
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