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Study of Pharmaceuticals Degradationby Advanced Oxidation Processes
Bílková, Zuzana ; Čáslavský, Josef (referee) ; Beklová, Miroslava (referee) ; Zachariášová,, Milena (referee) ; Vávrová, Milada (advisor)
At present, the issue of occurrence of female sex hormones, estrogens and progestogens, in aquatic ecosystems is often discussed by experts and the general public. These substances of steroid structure can be difficult to remove completely by conventional wastewater and drinking water treatment technologies. In given context advanced oxidation processes based on in situ generation of highly reactive hydroxyl radicals can be a suitable technique. This thesis deals with the study of kinetics and degradation products of photocatalytic decomposition of seven female sex hormones (estrone, -estradiol, estriol, ethinylestradiol, diethylstilbestrol, progesterone and norethindrone). Experiments were conducted in a laboratory glass reactor, which was equipped with an energy efficient UV-A LED light source (365 nm emission wavelength) and an immobilised photocatalyst in a form of TiO2 five-layer film deposited on glass. Model samples of water with the initial hormone concentration of 1 mg·L-1 were used and the degradation process was monitored by an HPLC-MS method. In the given system all compounds of interest except estriol had very significant tendency to be adsorb. In the case of estriol the formal rate constant of photocatalytic decomposition was determined based on the Langmuir-Hinshelwood model for two different initial concentrations, 0.5527 hour-1 (1 mg·L-1) and 0.1929 hour-1 (5 mg·L-1), and by comparison of these values it was found that the higher degraded compound concentration, the slower decomposition (fivefold increase of the initial concentration resulted in the constant decrease to almost one-third). Moreover nine degradation products of estriol photocatalytic decomposition were recorded and their structure was designed based on mass spectra. In the second thematic part of the thesis attention was paid to development of a SPE-HPLC-MS method for simultaneous determination of female sex hormones in water ecosystems, with emphasis on an extraction part optimization. The final samples treatment process included besides extraction with Supel™ Select HLB 200 mg SPE cartridges also mechanical impurities removal, hormones extraction from solids trapped on filtration material, sample acidification and extract purification with Supelclean™ ENVI-Florisil® cartridges. Optimised method was used for determination of female sex hormones in two Brno rivers, Svitava and Svratka. In the most cases the concentration was below the detection or quantification limit.
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Degradation of pyrethroids using heterogeneous catalysts
Janík, Ondřej ; Bílková, Zuzana (referee) ; Vávrová, Milada (advisor)
This thesis was provided to study fotocatalytic degradation of polutants on the titanium dioxide, as modern eliminating method useful for removing of polutants out of the environmental matrix. There are also studied pyrethroids, as one of the most used pesticides in recent ages, and posibility of degradation of pyrethroids using degradation on titanium dioxide in aquatic system. This study contains an experiment of fotocatalytic degradation of pyrethroids on titanium dioxide in vitro with final analysis using GC-ECD.
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The role of UDP-glycosyltransferase in development of drug resistance in parasitic nematodes
Dimunová, Diana ; Matoušková, Petra (advisor) ; Bílková, Zuzana (referee) ; Kašný, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Diana Dimunová Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of Doctoral Thesis: The role of UDP-glycosyltransferases in drug resistance in parasitic nematodes The diseases caused by parasitic nematodes represent a serious problem, which threatens livestock's health, because pharmacotherapy is complicated by widespread anthelmintic resistance. Understanding of the mechanisms of parasite drug resistance and defense strategies is important to maintaining the effectiveness of currently used anthelmintics and developing new approaches to controlling these infections. The ability of parasites to inactivate anthelmintics through their metabolism, which is provided by biotransformation enzymes, may contribute to the development of drug resistance. The UDP-glycosyltransferases (UGT) superfamily can protect parasites from the toxic actions of anthelmintics by modifying drugs to inactive glycoside metabolites. These metabolites have been identified in benzimidazole metabolism to an increased extent in a resistant strain of H. contortus, which suggests the involvement of UGTs in anthelmintic resistance. In the genome of this parasitic nematode, 32 genes encoding UGTs divided into 15 families have...
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The role of UDP-glycosyltransferase in development of drug resistance in parasitic nematodes
Dimunová, Diana ; Matoušková, Petra (advisor) ; Bílková, Zuzana (referee) ; Kašný, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Diana Dimunová Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of Doctoral Thesis: The role of UDP-glycosyltransferases in drug resistance in parasitic nematodes The diseases caused by parasitic nematodes represent a serious problem, which threatens livestock's health, because pharmacotherapy is complicated by widespread anthelmintic resistance. Understanding of the mechanisms of parasite drug resistance and defense strategies is important to maintaining the effectiveness of currently used anthelmintics and developing new approaches to controlling these infections. The ability of parasites to inactivate anthelmintics through their metabolism, which is provided by biotransformation enzymes, may contribute to the development of drug resistance. The UDP-glycosyltransferases (UGT) superfamily can protect parasites from the toxic actions of anthelmintics by modifying drugs to inactive glycoside metabolites. These metabolites have been identified in benzimidazole metabolism to an increased extent in a resistant strain of H. contortus, which suggests the involvement of UGTs in anthelmintic resistance. In the genome of this parasitic nematode, 32 genes encoding UGTs divided into 15 families have...
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Posttranslational modification of proteins - their analysis and physiological aspects
Mikulíková, Kateřina ; Mikšík, Ivan (advisor) ; Bílková, Zuzana (referee) ; Glatz, Zdeněk (referee)
This thesi s is eoneerned with the deteetion of posttranslational modifieation of proteins. These proteins are identified using liquid ehromatography and eapillary eleetrophoresis, their eoupling and eoupling to mass speetrometry. The first part of the theoretieal ehapter is devoted to the strueture, classifieation and metabolits ehanges of proteins in the human body. Major attention is foeused on eollagen, its strueture and individual eollagen types. The seeond part eonsiders the problems of nonenzymatie glyeation and its influenee on the body and engage in produets of posttranslational modifieation. The third part summarizes the individual separation proeedures and analysis of posttranslationaly modified proteins. The seeond ehapter deseribes experimental parameters, including ehemieals, instrumentation, materials and methods. The preparation of individual samples is also deseribed. All results and findings are summarized and diseussed in the last ehapter. This ehapter is divided in two parts. The first part foeuses on problems of in vivo experiments. The seeond part foeuses on problems of in vitro experiments. Powered by TCPDF (www.tcpdf.org)
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Optimization of purification of human membrane-bound carbonyl reductase.
Andrýs, Rudolf ; Wsól, Vladimír (advisor) ; Bílková, Zuzana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Rudolf Andrýs Supervisor: prof. Ing. Vladimír Wsól, Ph.D Title of diploma thesis: Optimalization of purification of a human membrane-bound carbonyl reductase Carbonyl reductases are enzymes participating in metabolic pathways of various eobiotics and xenobiotics. Of all known enzymes metabolizing xenobiotics only 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is found in the microsomal membrane. It also contributes to metabolism of prochiral anticancer drug oracin, which main metabolic pathway is a carbonyl reduction on the position 11 leading to two enantiomers of (+) an (-) 11-dihydrooracin (DHO). Based on the discrepancy between microsomes and 11β-HSD1 stereospecifity of oracin reduction exist a hypothesis of participation an unknown microsomal enzyme in oracin metabolism. The aim of this study is to purify a new microsomal carbonyl reducing enzyme contributing in the biotransformation of oracin. Human liver microsomes were solubilised and desalted. The prepared sample was used for the first purification step on Q-Sepharose. Captured flow through fraction Q2 was loaded on Phenyl-sepharose. Captured suitable fraction P11 was used for third purification step by gel filtration. All...
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The Role of Reductases in Cancer.
Škarydová, Lucie ; Wsól, Vladimír (advisor) ; Hodek, Petr (referee) ; Bílková, Zuzana (referee)
Only a small attention was paid for long time to reducing enzymes, but today it is clear that these are an important part of the endogenous metabolism and also the phase I biotransformation of xenobiotics. The significant group of reducing enzymes are carbonyl reductases that belong to two superfamilies - short chain dehydrogenases/reductases (SDR) and aldo-keto reductases (AKR). Their role in cancer is now intensively studied and their functions in cancer it is possible to divide into two main sections. It is known that carbonyl reductases play a substantial role in hormone-dependent cancers as prostate, breast or endometrial cancer. Active estrogens or androgens are important growth factors for these cancers because they evoke increasing of cell proliferation so that elevated possibility of mutations of important genes and development of cancer. Carbonyl reductases along with other enzymes (e.g. aromatase) participate in formation of these active sex hormones in extragonadal tissues, so an inhibition of such enzymes may be a target of anticancer therapy of hormone-dependent cancers. It is necessary to determine which enzymes are essential for the formation of active sex hormones in particular types of cancers. Besides hormone-dependent cancers, carbonyl reductases play also role in cancers that...
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