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Cytostatic Pharmaceuticals in the Environment, Methods for Their Elimination
Šídlová, Petra ; Skálová, Lenka (advisor) ; Boušová, Iva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Petra Šídlová Consultant: Doc. RNDr. Lenka Skálová, Ph.D. Title of Thesis: Cytostatic pharmaceuticals in the environment, methods for their elimination Recently there is an increasing interest in studying the effects of drugs used in human and veterinary medicine on the environment. Pharmaceuticals and their metabolites are excreted by patients into wastewater in considerable amounts. Conventional methods of wastewater treatment are often unable to fully eliminate these substances. Pharmaceuticals and their metabolites can get into the environment and affect the ecosystem. One way to streamline wastewater treatment is the application of phytoremediation technology in the form of root plants. In this work, the ability of plants to accumulate and degrade the cytostatic drug doxorubicin was studied. At the same time phytotoxic effects of this substance were monitored. For this purpose different systems of cultivation of plants were used: hydroponics in common reed (Phragmites australis (Cav.) Steud.), in vitro cultivation for Grey rushes (Juncus inflexus L.) and Arabidopsis (Arabidopsis thaliana L.) and cell culture suspension of linseed (Linum usitatissimum L.). Concentrations of...
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Inihibice glukuronidace léčiv extrakty a obsahovými látkami třezalky tečkované (Hypericum perforatum) a tymiánu obecného (Thymus vulgaris)
Čejchanová, Jana ; Boušová, Iva (advisor) ; Szotáková, Barbora (referee)
Charles University in Prague Julius-Maximilians-University Würzburg Fac. of Pharmacy in Hradec Králové Institute of Pharmacy and Food Chemistry Dept. of Biochemical Sciences Dept. of Pharmaceutical Chemistry Candidate: Jana Čejchanová Supervisor: PharmDr. Iva Boušová, Ph.D. PD Dr. Matthias Unger Title of diploma thesis: Inhibition of Drug Glucuronidation by Extracts and Constituents of St. John's wort (Hypericum perforatum) and Thyme (Thymus vulgaris) The issue of herb-drug interactions is discussed in last years more than ever before due to all over the world increasing popularity of herbal drugs. Whereas the awareness of herbal drugs interactions with cytochrome P450 is quite broad, the issue of their interaction with UDP-glucuronosyltransferase (UGT) enzymes, one of the main participants of the second phase metabolism in humans, is still full of questions. This work is focused on medicinal herbs St. John's wort (Hypericum perforatum) and thyme (Thymus vulgaris) and their impact on glucuronidation in the in vitro studies. The HPLC method for fractionation of herbal extracts was developed. The inhibitory activity of herbal extracts, individual fractions, and selected constituents on UGT was studied in human liver and/or human intestinal microsomes using model substrate TFMU...
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Drug-resistance in parasitic helminths
Mertová, Petra ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Science Candidate: Petra Mertová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Drug-resistance in parasitic helminths The development of drug resistance in parasitic helminths poses a large threat to productivity in livestock and the control of human helminths in future. Currently there are three broad spectrum classes of anthelmintics: the benzimidazoles, the imidazothiazoles (levamisole) and the tetrahydropyrimidines (pyrantel, morantel), the macrocyclic lactones (avermectins and milbemycins). Benzimidazoles act by specific binding to parasites β-tubulin, resistance in this class of anthelmintics appears to be associated with mutations in β-tubulin genes. Resistance to levamisol or pyrantel, drugs which act as an agonist at nicotinic acetylcholine receptors, is probably caused by amount reduction or by loss of affinity in these receptors. Macrocyclic lactones mode of action is not fully understood, but there appears to be relation with modulating glutamate-gated chloride channels present on muscle membranes of the parasites. Recent studies revelead that P-glycoprotein and others ATP transporters are involved in anthelmintic resistance. Modes of action and factors influencing the...
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Sojové isoflavonoidy, genistein a daidzein: Jejich biologické efekty na buněčné linie rakoviny prsu
Hůrková, Kristýna ; Šimůnek, Tomáš (advisor) ; Boušová, Iva (referee)
- 1 - ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kristýna Hůrková Supervisors: Profa . Dra . Natércia Teixeira, Profa . Dra . Georgina Correia da Silva, Doc.Pharm.Dr. Tomáš Šimůnek Ph.D. Title of diploma thesis: Soya isoflavones, genistein and daidzein: Their biological effects on breast cancer cell lines Cancer is one of the leading causes of death worldwide. Epidemiological studies suggested that there is a low incidence of breast cancer in countries with high soya intake. Soya contains the isoflavones daidzein (D) and genistein (G), which are responsible for the protective properties, although their exact effects have not yet been clarified. In this study we evaluated and compared the biochemical and biological effects of a soya extract biotransformed by Aspergillus Awamori (SBE) and of the pure major isoflavones, G and D in placental microsomes and in an estrogen-dependent breast cancer cell line stably transfected with the aromatase gene, the MCF-7aro cell line. The results showed that D did not induce marked alterations in any of the parameters studied. In placental microsomes G was not a potent aromatase inhibitor, inducing only a moderate reduction in the aromatase activity. In MCF-7aro cells it was observed a significant...
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Investigation of sugar modified pyrimidine nucleosides as potential inhibitors of Thymidine (TP) and Uridine (UP) phosphorylasis
Růžičková, Markéta ; Wsól, Vladimír (advisor) ; Boušová, Iva (referee)
1 Abstract of the thesis RŮŽIČKOVÁ M.; INVESTIGATION OF SUGAR MODIFIED PYRIMIDINE NUCLEOSIDES AS POTENTIAL INHIBITORS OF THYMIDINE (TP) AND URIDINE (UP) PHOSPHORYLASE Key words: uridine phosphorylase, thymidine phosphorylase, nucleoside, inhibitor, anticancer chemotherapy, substrate specifity The work deals with the investigation of novel potential inhibitors of recombinant thymidine and uridine phosphorylases from E. coli and Salmonella typhimurium. The main goals of this study are the determination of kinetic parameters for natural substrates (thymidine and uridine) for recombinant TP and UP, assessment of the role of phosphate anion in the enzymatic transformations and search for new inhibitors of TP and UP. Study of UP and TP substrate specifity and activity under the various reaction conditions is desired to obtain better view to their functions and to design novel structures of potencial inhibitors. The determination of the Michaelis constant KM and reaction rate Vmax was performed at the spectrophotometer Varian Cary-300 Bio. The representation of obtained kinetic data we used the Lineweawer-Burk plot. The next point of my work was the determination of the enzymatic activity and their substrate specifity for some pyrimidine analogues by HPLC analysis of reaction mixtures. Tested compounds...
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Effect of compounds with antioxidant properties on glycation of aspartate aminotransferase
Bacílková, Eliška ; Boušová, Iva (advisor) ; Dršata, Jaroslav (referee)
Publishing place: Charles University in Prague, Faculty of Pharmacy in Hradec Králové Author: Eliška Bacílková Title: Effect of compounds with antioxidant properties on glycation of aspartate aminotransferase Supervisor: PharmDr. Iva Boušová, Ph.D. In this diploma thesis, I was concerned with the direct and indirect effects of uric acid, aminoguanidine, and hydroxycitric acid on enzymatic activity of aspartate aminotransferase and on its glycation by methylglyoxal. The catalytic activities were measured by kinetic UV method. Stabilities of aminoguanidine and uric acid, their interactions with the molecule of enzyme and influence on formation of glycation products were observed by absorption spectroscopy. Although aminoguanidine decreased enzymatic activity in higher concentration, it showed positive indirect effects on glycation of aspartate aminotransferase and it also decreased amount of rising glycation products. Hydroxycitric acid did not have negative direct effect on enzyme activity and was partially able to protect enzyme from glycation by methylglyoxal. Uric acid exerted neither negative direct nor positive indirect effects. Aminoguanidine and uric acid were stable during experiment and reacted with molecule of protein, which was expressed by modifications of its UV-VIS spectra in the area...
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