Rigorous theses

Rigorous theses 15,322 records found  beginprevious21 - 30nextend  jump to record: Search took 0.00 seconds. 
Development of Czech water law and legal relations related to water
Urban, Michael ; Blažek, Lukáš (referee)
Development of Czech water law and legal relations related to water Abstract This dissertation thesis deals with the development of the legal regulation of water law and legal relations related to water in the Czech Republic. It provides an interpretation of the issue from the beginnings of the Czech state to the present. The thesis is divided into sixteen chronological chapters focusing on individual periods of development of this issue. The individual chapters are divided into sub-chapters dealing with sub-fields of water law and legal relations related to water. The first four chapters provide a theoretical introduction and a common basis for the other chapters. The first chapter contains an analysis of the concept of water law and the systematics of water law. The second chapter provides an outline of the development of water law in antiquity as an illumination of the earliest roots of water law. The third chapter discusses the foundations and structure of Roman water law as the methodological basis of the field of water law. The fourth chapter deals with the basic features of the development of water law in the territory of states neighbouring the Czech Republic. Chapters 5-15 form the core of the thesis and deal with individual periods of development of Czech water law and legal relations related to...
The use of selected inhibitors to overcome anthracycline resistance in cancer therapy (in vitro study).
Tučková, Kateřina ; Wsól, Vladimír (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Tučková Supervisor: prof. Ing. Vladimír Wsól, Ph.D. Consultant: Mgr. Lenka Laštovičková, Ph.D. Title of diploma thesis: The use of selected inhibitors to overcome anthracycline resistance in cancer therapy (in vitro study) Resistance to chemotherapy is a severe problem in treating cancer patients, significantly reducing their chances of recovery. The increased expression of carbonyl reductases in tumour cells is one of the leading causes of the resistance. These enzymes can reduce anthracycline-based chemotherapy drugs to their less effective derivatives and thus significantly reduce their efficiency. Therefore, the inhibitors of carbonyl reductases could increase the effectiveness of anthracycline-based chemotherapy. The goal is to find an inhibitor with high inhibitory activity and low side effects. This thesis tested inhibitors asciminib, tucatinib, sotorasib, and umbralisib hydrochloride against carbonyl reductases from the aldo-keto reductase superfamily (AKR1C3, 1A1, 1B1, 1B10) and short-chain dehydrogenases/reductases superfamily (CBR1), using chemotherapy drug daunorubicin. The most significant inhibitory potential was observed between asciminib and the enzyme AKR1C3,...
Preparation of STAT3-knockout glioblastoma multiforme cell line using CRISPR-Cas9 editing
Papinčáková, Dominika ; Skálová, Lenka (advisor) ; Laštovičková, Lenka (referee)
Charles University Fakulty of Pharmacy in Hradec Králove Department of Biochemical Sciences Candidate: Bc. Dominika Papinčáková Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Preparation of STAT3-knockout glioblastoma multiforme cell line using CRISPR-Cas9 editing Glioblastoma multiforme (GBM) is one of the most common primary brain tumours in adults and one of the most fatal cancers in humans A key oncogene in GBM development and progression is the signal transducer and activator of transcription 3 (STAT3). It is one of the mediators of tumorigenesis, plays a strong pro-survival role in GBM, and is permanently activated in GBM, leading to increased cell proliferation, invasiveness, and angiogenesis. The aim of this work was to establish a GBM STAT3-knockout (STAT3-KO) cell line. The U87MG cell line and the CRISPR-Cas9 gene knockout method were used for this purpose. In a first step, we investigated the possibility of silencing STAT3 expression by siRNA and the suitability of this cell type to pinpoint the mechanism for CRISPR gene editing into the cell. In the second step, we transfected the cells using the STAT3 gene knockout kit (CRISPR) and tested the knockout success. In the established STAT3-KO GBM cell line, we confirmed STAT3-KO at the DNA, RNA and protein levels. We...
Functionalized hyper-cross-linked porous polyacetylenes
Havelková, Lucie
An atom-economic one-step chain-growth coordination homopolymerization providing high yields of functionalized hyper-cross-linked polyacetylenes with permanent micro/mesoporous texture and specific surface area up to 1062 m2 /g was introduced and optimized. Substituted 1,3-diethynylbenzenes served as monomers simultaneously providing functionalization and hyper-cross-linking of the networks. The homopolymerization was compatible with the heteroatom groups of the monomers and allowed to prepare polyacetylene networks with the wide spectrum of univalent functional groups: -F, -Cl, -Br, -NO2, -COOCH3, -CH2OH, -COOH and -CH=O decorating the aromatic segments of the networks in a high extent (7.87 mmol/g). A novel two-step synthesis of functionalized hyper-cross-linked polyacetylenes was introduced combining chain-growth coordination polymerization of acetylenic monomers and covalent templating using acetal and Schiff base protecting groups. By postpolymerization hydrolytic removal of the protecting segments from the primary networks, the networks with a high content (up to 9.61 mmol/g) of univalent functional groups -CH2OH, -CH=O and -NH2 were prepared. These groups were placed either on the cross-linking or linear (aromatic and aliphatic) network segments, even in the vicinity of the main...
The efflux transport activity of P-glycoprotein - 9.2 fromHaemonchus contortus
Kohoutová, Kateřina ; Matoušková, Petra (advisor) ; Boušová, Iva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Kohoutová Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of diploma thesis: The efflux transport activity of P-glycoprotein-9.2 from Haemonchus contortus Haemonchosis is a globally widespread disease affecting small ruminants. The causative agent of the disease is the gastrointestinal nematode Haemonchus contortus, which feeds of the blood of its host. The treatment of haemonchosis with anthelmintics is complicated by the worldwide spread of resistance. One possible cause of the development of anthelmintic resistance is a decrease in anthelmintic concentration in the worm due to increased expression of P-glycoproteins from ABC transporter superfamily. The study of the transport activity of these transporters could help to understand the mechanism of resistance development and make the treatment of haemonchosis more effective. The aim of this thesis was to characterize the transport activity of P-glycoprotein-9.2 and its interaction with a selected inhibitor using a heterologous expression system. The adherent cell line HEK293 was transfected with a plasmid carrying the Pgp-9.2 gene of the Haemonchus contortus. Successful expression was verified by dot blot. Unfortunately,...
Study of migration of cells affected by sulfur mustard
Mojská, Mária ; Macháček, Miloslav (advisor) ; Fikrová, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mária Mojská Supervisor: RNDr. Miloslav Macháček, PhD. Consultant: Mgr. Petr Jošt, PhD. Title of diploma thesis: Study of the migration of cells affected by sulfur mustard Sulfur mustard is a highly toxic chemical agent. From the point of view of toxicology, it is classified as a blistering agent, and its use is prohibited by the Chemical Weapons Convention. However, this substance has been used in several armed conflicts and terrorist attacks in the past. When it comes in contact with human skin, it produces typical blisters filled with a yellowish exudate. Sulfur mustard has cytotoxic and cytostatic effects on living tissue, and therefore the treatment of such lesions is extremely difficult. This thesis is focused on the in vitro evaluation of the possibility of employing growth factors IGF, KGF, and EGF in the wounding process of sulfur mustard-damaged tissue. The effect of these growth factors on collective migration of HaCaT keratinocytes and HDFa skin fibroblasts under in vitro conditions was evaluated using the "scratch wound healing assay" method. Our results show that the toxic effects of sulfur mustard inhibit cell migration to such an extent that the positive effect of the growth...
Monitoring the transfer of albendazole from the sheep faeces to fodder by LC-MS
Sochová, Andrea ; Skálová, Lenka (advisor) ; Matysová, Ludmila (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Andrea Sochová Supervisor: prof. RNDr. Lenka Skálová, Ph. D. Title of diploma thesis: Monitoring of albendazole transfer from ovine faeces to fodder plants by LC-MS In general, drugs might be a significant source of pollution in the environment especially drugs with high persistence. Albendazole (ABZ) belongs to a benzimidazole group of anthelmintic drugs. These drugs are regularly and frequently used to limit and treat parasitic infections in animals. ABZ enters the environment via animal excrements and it can have negative effects on non-target organisms. Laboratory experiments have shown that the plants can uptake and even biotransform the ABZ, however, it is not known whether these phenomena occur in the real field conditions. The present study monitors the transfer of ABZ and its transformation products (TPs) from the faeces of treated sheep to common fodder plants such as Medicago sativa and Trifolium pratense. We wanted to know whether the possibility of transferring these compounds from excrement into the soil and from soil to plants exits in real field conditions. Our study successfully revealed the occurrence of ABZ TPs (ABZ-SO and ABZ-SO2) in both fodder plants. The highest...
Methodology of investigating drug crimes with a focus on production of methamphetamine
Vávra, Vojtěch ; Beranová, Andrea (referee)
Methodology of investigating drug crimes with a focus on production of methamphetamine Abstract This thesis deals with methodology of investigating drug crimes with a focus on production of methamphetamine. Considering the complexity of the mentioned topic, it takes into account substantive and procedural criminal law, criminalistics, criminology and addictology. In the first chapter, in addition to describing the forms, effects and methods of methamphetamine production, with an emphasis on the Czech way of methamphetamine production, the historical genesis of the problem is also presented. The second chapter defines the terms small-scale production, medium-level production and large-scale production in order to increase legal certainty. The thesis draws inspiration from the current methodology of the National Drug Headquarters and the United Nations. This part of thesis also includes a statistical section dealing with the structure of drug crime in terms of prosecutions and seized clandestine laboratories. The third chapter describes a typical drug offender. The offenders are divided according to their level of professionalism into three groups: amateur, semi-professional and professional. This paper also discusses individual roles in an organized group, which it classifies as mandatory and optional in...
Determination of ganciclovir in lung transplant recipients
Hrach, Filip ; Szotáková, Barbora (advisor) ; Kotaška, Karel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Filip Hrach Supervisor: prof. Ing. Barbora Szotáková, Ph.D. Consultant: doc. Ing. Eva Klapková, Ph.D. Title of diploma thesis: Determination of ganciclovir in lung transplant recipients Ganciclovir is a nucleoside analogue that is widely used for the treatment of infections caused by herpes viruses, including cytomegalovirus. Patients after lung transplantation are always given valganciclovir (ganciclovir prodrug) prophylactically to prevent cytomegalovirus infection. The aim of this thesis was to establish a reliable, sensitive and rapid analytical method for the determination of ganciclovir and to validate this method. Furthermore, to determine ganciclovir levels in patients after lung transplantation. The final objective was to evaluate the importance of therapeutic monitoring of ganciclovir. A liquid chromatography-tandem mass spectrometry method was established for the determination of ganciclovir. Validation parameters necessary for bioanalytical methods have been established.All validation parameters met the conditions for successful validation.Valganciclovir is used for oral administration of antiviral drugs and ganciclovir for intravenous administration. Patients after lung...
The changes in flubendazole metabolism during life cycle of nematode
Salvová, Martina ; Skálová, Lenka (advisor) ; Prchal, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Martina Salvová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in flubendazole metabolism during life cycle of nematode The nematode barber's pole worm (Haemonchus contortus) is an infectious pathogen that causes gastrointestinal haemonchosis in ruminants. Its life cycle consists of egg, larval (L1, L2 and L3) and adult stages. Haemonchosis is a common and widespread disease of farm animals, which causes significant global economic losses. Whereas the treatment of haemonchosis is mainly based on pharmacotherapy using anthelmintics, the increasing drug resistance of barber's pole worm to these drugs is a big problem. Hence, the study of the mechanisms of the development of drug resistance in this parasite is in the foreground of scientific interest. One of the mechanisms of resistance may be an increased ability to deactivate the anthelmintics. In the case of the benzimidazole anthelmintic flubendazole, deactivation is based on a reduction of the carbonyl group by the enzymes aldo-ketoreductases and short-chain dehydrogenases/reductases. The metabolite with decreased anthelmintic efficacy is produced by the reduction of flubendazole, and in this way, nematodes...

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