National Repository of Grey Literature 4 records found  Search took 0.00 seconds. 
Tandemová hmotnostní spektrometrie sfingolipidů s aplikací pro metabolické studie a diagnostiku sfingolipidos
Kuchař, Ladislav ; Ledvinová, Jana (advisor) ; Stiborová, Marie (referee) ; Holčapek, Michal (referee)
In recent years, mass spectrometry (MS) become the dominant technology in lipidomic analysis and widely influenced research and diagnosis of diseases of lipid metabolism, e.g. lysosomal storage disorders (LSD) characterized by impairment of the lysosomal functions. Defects in lysosomal processing of sphingolipids SFL belong to the category of sphingolipidoses. This condition has severe and even fatal clinical outcome. The primary aim of this work was to establish quantitative and qualitative methods of SFL analysis useful for research and diagnosis of LSD. At first, semisynthesis of mass labeled lipid standards utilizing immobilized sphingolipid ceramide N-deacylase was performed. Established methods of quantitative analysis were then used to prove the increased excretion of urinary SFL in LSD with characteristic storage in the kidney. Determination of excreted urinary SFL was found useful for differential diagnosis of prosaposin and saposin B deficiences for which routine enzymology is failing. MS also enabled monitoring of individual molecular species (isoforms) of SFL, which led to the finding that their urinary pattern is changing in some LSD. This resulted in the development of new screening method in dry urinary samples based on isoform profile evaluation. Another MS application referred to...
Metabolic study of sibutramine
Link, Marek ; Wsól, Vladimír (advisor) ; Holčapek, Michal (referee) ; Nobilis, Milan (referee)
Obesity represents a serious problem especially in American and European populations. Pharmacotherapy in combination with a reduced calorie diet is recommended for obese patients as a multi-modal approach to weight loss. Sibutramine hydrochloride monohydrate represents one of the few established and well-proven agents available for treatment of obesity. It is sold as a racemic mixture under the trade-name Meridia, Reductil or Lindaxa. It acts as a monoamine reuptake inhibitor. The weight loss of patients induced by sibutramine is thought to be due to a combination of serotonin- and noradrenaline-mediated mechanisms that increase both satiety and energy expenditure. In organisms, sibutramine is rapidly demethylated to form metabolites M1 and M2. These metabolites contribute largely to the pharmacological effects of sibutramine and the pharmacokinetic characteristics of M1 and M2 were thoroughly studied in human plasma. Although sibutramine is widely used for the treatment of obesity almost ten years, the published information on the further metabolic fate of metabolites M1 and M2 as well as on the elimination of sibutramine from the body is almost exclusively limited to package inserts of the product. To address this issue we determined the routes of elimination of sibutramine in humans via urine. LC-API/MS...
Analytical Evaluation of Biologically Active Substances by Chromatographic Methods
Pasáková, Ivana ; Sochor, Jaroslav (advisor) ; Nobilis, Milan (referee) ; Holčapek, Michal (referee)
Introduced dissertation thesis deals with the development and validation of the chromatographic methods for analytical evaluation of selected biologically active substances. HPLC coupled with UV and MS detection was chosen for determination of analytes, because of the dominant role of the HPLC in pharmaceutical analysis. The theoretical part is focused on the theory of chromatographic methods and topics of the experimental work. At first, summary of all the chromatographic methods is briefly introduced and subsequently, the most common analytical method HPLC is described in details. The next part deals with the mass spectrometry. Thank to its high sensitivity and ability to provide structural information about the analytes, MS became an indispensable tool not only in modern pharmaceutical analysis. Besides MS theory and instrumentation, its applications and new trends are also mentioned. Last chapters deal with the transdermal application of drugs, specifications of antiretroviral therapy and especially they provide basic information about the physical - chemical and biological properties of analysed substances. The experimental part is consisted of the original research papers with appropriate comments divided into two thematic sections. The first one is composed of three papers focused on analytical...
The metabolism of anthelmintics for helminth
Cvilink, Viktor ; Skálová, Lenka (advisor) ; Holčapek, Michal (referee) ; Machala, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Viktor Cvilink Supervisor: Doc. RNDr. Lenka Skálová, Ph.D. Title of Doctoral Thesis: METABOLISM OF ANTHELMINTICS IN HELMINTHS Anthelminthic drugs are presently the principal method for the control of helminth diseases. Knowledge of detoxification mechanisms that helminths possess is important for understanding the processes that affect the drug concentration within a helminth organism and may be crucial in the treatment efficacy. When the drug concentration in a target organism does not reach the therapeutic level, it results in a decreased efficacy of pharmacotherapy which may further lead to the induction of helminth biotransformation enzymes and eventually issue in resistance development to the administered drug. Present knowledge of helminth biotransformation enzymes is insufficient. Often it is not known whether a given individual helminth species possesses such enzymes or whether it is capable of employing them in treatment evasion. In the presented thesis, the objective was to investigate the biotransformation pathways of selected anthelminthics in model helminth species, identify the formed metabolites and characterize biotransformation enzymes of the studied parasites. Our...

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