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Factors Affecting Metabolism of Anthelmintics
Forstová, Veronika ; Skálová, Lenka (advisor) ; Machala, Miroslav (referee) ; Chládek, Jaroslav (referee)
Nowadays, anthelmintic therapy is the main method in the fight with parasitic worms. Anthelmintics, as well as other xenobiotics, undergo structural changes by effect of biotransformation enzymes, when lipophilic substances are transformed to polar substances more easily eliminable from the organism. Generally, biological effects of metabolites and parent compound are different. Activity of biotransformation enzymes is thus the fundamental factor influencing velocity of detoxification and elimination of the compound from the body and duration of drug effect as well. Modulation of biotransformation enzymes' activities can lead to changes in pharmacokinetic parameters of drug itself as well as other xenobiotics and thus to the risk of decrease in desired effect and/or increase in adverse effects with corresponding impact on the quality of drug therapy. In addition, possible risk of drug residues' presence in animal products has to be considered in farm animals. Biotransformation of xenobiotics is affected by many physiological as well as pathological factors. These factors can be divided into inter-individual (species, gender, genetic polymorphism) and intra-individual (age, diet, medication, disease, etc.). All these factors cause wide variability in occurrence and activity of biotransformation...
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Oxidative damage by organic extracts from urban air particulate matter
Hanzalová, Kateřina ; Rössner, Pavel (advisor) ; Machala, Miroslav (referee)
The aim of this master thesis was to investigate the ability of selected individual carcinogenic polycyclic aromatic hydrocarbons (c-PAHs: benzo[a]pyrene, B[a]P; dibenzo[a,l]pyrene, DB[a,l]P), an artificial mixture of c-PAHs (c-PAH mix) and extractable organic matter (EOM) from urban air particulate matter (PM) to induce oxidative damage in vitro. Two cell lines (human hepatoma cells, HepG2, and human diploid lung fibroblasts, HEL) were treated for 24 h and 48 h with various concentrations of compounds or mixtures. The studied oxidative stress markers included 8-oxodeoxyguanosine (8-oxodG) as a marker of oxidative DNA damage, 15-F2t-isoprostane (15-F2t-IsoP) as a marker of lipid peroxidation and protein carbonyl groups as a marker of oxidative damage to proteins. The response of the cell lines to the tested compounds and mixtures differed substantially. In summary the results demonstrate the ability of EOM to induce oxidative damage to DNA and lipids after 24 h of treatment and to proteins after 48 h, in HepG2 cells. The effect of c-PAHs was substantially less. The induction of oxidative damage by c- PAHs and EOM in HEL cells was weak. Since c-PAHs had lower ability to cause oxidative damage that was limited only to longer incubation periods, it is probable that other components of EOM are responsible for...
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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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Ancient coppice woodlands - methodology of inventory, evidence and management
Maděra, Petr ; Buček, Antonín ; Úradníček, Luboš ; Slach, Tomáš ; Friedl, Michal ; Machala, Martin ; Řepka, Radomír ; Lacina, Jan ; Černušáková, Linda ; Volařík, Daniel
Methodology is focused on suggestion how to do an inventory, evidence and management of ancient coppice woodlands. Ancient coppice woodlands are defined as longterm and continuously coppiced forest stands.
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Single particle analysis of size-segregated aerosol in Prague city center
Marvanová, S. ; Skoupý, Radim ; Kulich, P. ; Bendl, J. ; Hovorka, J. ; Machala, M.
Particulate matter (PM) is omnipresent pollutant in the ambient air known to cause cardiovascular and respiratory diseases (WHO 2004). Recently, outdoor air pollution and particulate matter in outdoor air pollution were classified as carcinogenic to humans, Group 1 (IARC 2015). Especially, ambient PM of aerodynamic diameter < 100 nm, ultrafine particles, appears to be of great importance due to its high specific surface area and high number concentration (Hughes et al. 1998). Ultrafine particles also easily enter and are being transferred in organisms, and interact with cells and subcellular components (Oberdorster et al. 2005). As the evidence of ultrafine PM significance increased, size-fractionated PMs sampled by various cascade impactors have been employed into the toxicological studies on cell cultures or isolated cells, using the organic extracts of size-fractionated PMs (Topinka et al. 2013, Topinka et al. 2015) or directly the size-fractionated particles (Becker et al. 2003, Ramgolam et al. 2009, Reibman et al. 2002, Loxham et al. 2013, Jalava et al. 2006, Thomson et al. 2015, Jalava et al. 2015). The aim of this study was to evaluate shape and composition of size-segregated aerosol particles, sampled by high volume cascade impactor, using electron microscopy and energy dispersive X-ray spectroscopy (EDX).
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Modern methods of control of heating systems
Machala, Martin ; Weismanová, Júlia (referee) ; Štětina, Josef (advisor)
The aims of the thesis are modern methods of control of heating systems. Basic principles of regulations are explained and methods of control of heating sources and exchangers are explored. Heating system of family building is projected with two types of control – equithermal regulation with thermostatic heads and individual room control (IRC). Both variants are simulated in program TRNSYS 16.1. From the results are concluded advantages and disadvantages of examined systems of control.
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Operation and Competitive Advantages of VLJ Aircraft
Machala, Marek ; Mahovský, Daniel (referee) ; Kujal, Tomáš (advisor)
Master’s thesis deals with problematic of operating aspects and competitiveness of VLJ aircraft in Czech and Europe market. The Thesis contain information about different types of VLJ, their operational costs and comparisons with competitors, some information about aircraft fractional ownership and their operation. There is written a market analysis for this aircraft and air taxi service in analyzed.
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Marketing Strategy for the New Product Line
Machala, Martin ; Hačunda, Pavol (referee) ; Chlebovský, Vít (advisor)
Diploma thesis deals with the proposal of marketing strategy for an existing company, which is producing platforms for disabled people. This company will expand and distribute also lifts. The marketing strategy is based on the theory and analysis of the state of the company. Implementations should lead to getting into the awareness of new clients and entry of the company into a new market.
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