|
|
Study on potentiaion of pharmacological efficiencies of ellipticine
Vranová, Iveta ; Stiborová, Marie (advisor) ; Mrázová, Barbora (referee)
Cytotoxic chemotherapy offers tool for clinical treatment of neoplasia. One of the drugs suitable for chemotherapy is ellipticine. Ellipticine is an alkaloid, which has significant antineoplastic properties. It acts as a DNA intercalator, inhibitor of topoisomerase II and forms also covalent DNA adducts mediated by cytochrome P450 and/or peroxidases. Oxidation of ellipticine by CYP (CYP3A4, CYP1A1/2, CYP2C9, CYP1B1) provides several metabolites (7-hydroxyellipticine, 9-hydroxyellipticine, 12-hydroxyellipticine, 13- hydroxyellipticine, and ellipticine N2 -oxide). Metabolites 12-hydroxyellipticine and 13- hydroxyellipticine, formed by CYP3A4, are responsible for formation of two major DNA adducts. Two carbenium ions, ellipticine-13-ylium and ellipticine-12-ylium were proposed as a reactive species binding to DNA. The main metabolites generated by peroxidases are the ellipticine dimer and ellipticine N2 -oxide, which provide the same carbenium ions and same DNA adducts. Modern chemotherapy uses targeting for higher selectivity for malignant cells and lower cytotoxicity for normal cells. Ellipticine-conjugates and his derivates (N-(2-hydroxypropyl)methakrylamid-ellipticine conjugates, vasoactive intestinal peptide-ellipticine conjugates and human serum albumin-ellipticine conjugates) and epidermal...
|
|
|
The mechanism of action of anticancer drug ellipticin in target tissues of its effect
Vranová, Iveta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Ellipticine is an alkaloid isolated from Apocynaceae plants exhibiting significant antitumor and anti-HIV activities. Cytochromes P450 (CYP) and peroxidases are the enzymes participating in metabolism of ellipticine. This process provides activation and detoxication metabolites of ellipticine. The CYP enzymes, which participate in oxidation of ellipticine in different tissues (liver, lung and kidney) of rat, a model organism simulating the fate of ellipticine in humans have already been identified. In this work, the effects of ellipticine on contents and catalytic activities of CYPs and other components of the mixed-function oxidase (MFO) system in this animal system were studied. For detection of contents of CYPs and other components of the MFO system, spectroscopic and electrochemical methods were used. To determine catalytic activities of CYPs and NADPH:cytochrome P450 reductase, reactions with specific substrates of these enzymes were utilized. The results found in this study demonstrate that expression and catalytic activity of CYP1A is induced by ellipticine in all of the tested organs (liver, kidney and lung) of rats treated with the drug. Moreover in liver, the cytochrome b5 expression is also induced. In addition, in this organ, expression and catalytic activity of CYP3A was increased by...
|
|
|
The mechanism of action of anticancer drug ellipticin in target tissues of its effect
Vranová, Iveta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Ellipticine is an alkaloid isolated from Apocynaceae plants exhibiting significant antitumor and anti-HIV activities. Cytochromes P450 (CYP) and peroxidases are the enzymes participating in metabolism of ellipticine. This process provides activation and detoxication metabolites of ellipticine. The CYP enzymes, which participate in oxidation of ellipticine in different tissues (liver, lung and kidney) of rat, a model organism simulating the fate of ellipticine in humans have already been identified. In this work, the effects of ellipticine on contents and catalytic activities of CYPs and other components of the mixed-function oxidase (MFO) system in this animal system were studied. For detection of contents of CYPs and other components of the MFO system, spectroscopic and electrochemical methods were used. To determine catalytic activities of CYPs and NADPH:cytochrome P450 reductase, reactions with specific substrates of these enzymes were utilized. The results found in this study demonstrate that expression and catalytic activity of CYP1A is induced by ellipticine in all of the tested organs (liver, kidney and lung) of rats treated with the drug. Moreover in liver, the cytochrome b5 expression is also induced. In addition, in this organ, expression and catalytic activity of CYP3A was increased by...
|
|
|
Study on potentiaion of pharmacological efficiencies of ellipticine
Vranová, Iveta ; Mrázová, Barbora (referee) ; Stiborová, Marie (advisor)
Cytotoxic chemotherapy offers tool for clinical treatment of neoplasia. One of the drugs suitable for chemotherapy is ellipticine. Ellipticine is an alkaloid, which has significant antineoplastic properties. It acts as a DNA intercalator, inhibitor of topoisomerase II and forms also covalent DNA adducts mediated by cytochrome P450 and/or peroxidases. Oxidation of ellipticine by CYP (CYP3A4, CYP1A1/2, CYP2C9, CYP1B1) provides several metabolites (7-hydroxyellipticine, 9-hydroxyellipticine, 12-hydroxyellipticine, 13- hydroxyellipticine, and ellipticine N2 -oxide). Metabolites 12-hydroxyellipticine and 13- hydroxyellipticine, formed by CYP3A4, are responsible for formation of two major DNA adducts. Two carbenium ions, ellipticine-13-ylium and ellipticine-12-ylium were proposed as a reactive species binding to DNA. The main metabolites generated by peroxidases are the ellipticine dimer and ellipticine N2 -oxide, which provide the same carbenium ions and same DNA adducts. Modern chemotherapy uses targeting for higher selectivity for malignant cells and lower cytotoxicity for normal cells. Ellipticine-conjugates and his derivates (N-(2-hydroxypropyl)methakrylamid-ellipticine conjugates, vasoactive intestinal peptide-ellipticine conjugates and human serum albumin-ellipticine conjugates) and epidermal...
|
|
|
Perspectives of public contracts in the context of revision of the European Union’s law
Vránová, Iveta ; Ochrana, František (advisor) ; Vítek, Leoš (referee)
Diploma thesis with the topic "Perspectives of public contracts in the context of revision of the European Union's law", provides a summary of the most important changes brought by the transposition of the European Directive to the Czech Law. This thesis is based on the Public Contracts Directive 2014/24/EU, dated 26th February 2014, which replaced the previous Public Contracts Directive 2004/18/ES, and Directive 2014/25/EU, which replaced the Directive 2004/17/ES. The thesis deals with the reasons leading to the change of all mentioned Directives as well as with the "technical amendment" of the Public Procurement Act No. 137/2006 Coll., which has been in effect since the 1st of January 2014.
|
|
|
Selection and evaluation of public procurements
Vránová, Iveta ; Novotný, Jiří (advisor)
Bachelor thesis on the topic "Selection and evaluation of public procurements", mainly deals with problems that arise in the selection and subsequent evaluation of the public procurements. The entire procurement process is based on an amendment to the Public Procurement Act --Act No. 179/2010 Coll. (in the original version of Act No. 137/2006 Coll.). An analysis of the specific case of public procurement, and its evaluation with respect to the lowest bid and in line with economic expediency, is part of the thesis. The cardinal scale and a method of weighing of utility properties are applied in the analysis. The goal of the thesis is to determine an impact of the methods of the evaluation on the final ranking of the tenders.
|
guest ::
RSS feed.