National Repository of Grey Literature 13 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Design of production control for LEAN manufacturing
Machala, Miroslav ; Knoflíček, Radek (referee) ; Hromková, Ivana (advisor)
This bachelor theses deals with theoretical principles of lean manufacturing, consequently about its successful implementation into two real companies and their mutual comparison. At the beginning of these thesis the publication research is done as well as history summary, method descriptions, foreign applications and comparison of selected approaches. In the sec-ond part of the work the implementation into two Brno real companies is described. Both companies use chip forming cutting process but they have different type of production and batch size. It is designed innovative shop floor layout, innovated processes and new proce-dures in order to increase efficiency of each company.
Molecular mechanisms involved in genotoxicity of industrially important monomers (styrene, 1,3-butadiene)
Kuricová, Miroslava ; Vodička, Pavel (advisor) ; Černá, Marie (referee) ; Machala, Miroslav (referee)
1 ABSTRACT The evaluation of individual health risk in workers occupationally exposed to industrial xenobiotics requires the use of a large number of parameters reflecting external exposure, internal exposure, biological effects and individual susceptibility. Environmental, occupational and life style-related exposure to mutagenic agents may contribute to cancer risk in humans. To prevent the potentially hazardous effects of such agents it is important to understand their mechanisms of action. Styrene is one of the most important monomer for producing polymers and copolymers in plastics, latex paints and together with 1,3-butadiene (BD) in the manufacture of synthetic rubbers. In this thesis, a large set of parameters, including markers of external and internal exposure and biomarkers of biological effects and susceptibility have been studied in relation to the occupational exposure to both styrene and BD. First part of the present study was focused on evaluating the role of various biomarkers to assess genotoxic effects of above mentioned xenobiotics. Biomarkers reflecting styrene- and BD-induced genotoxicity and mutagenicity: O6 -styrene guanine DNA adducts, haemoglobin adducts, single-strand breaks (SSBs), SSB Endo III sites, chromosomal aberrations (CA), hypoxanthine-guanine phosphoribosyltransferase...
METABOLISM AND EFFECTS OF NEW ANTHELMINTIC DRUG IN HELMINTHS AND ITS HOSTS
Stuchlíková, Lucie ; Skálová, Lenka (advisor) ; Kučera, Radim (referee) ; Machala, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Lucie STUCHLÍKOVÁ Supervisor prof. RNDr. Lenka SKÁLOVÁ, Ph.D. Title of Doctoral Thesis METABOLISM AND EFFECTS OF NEW ANTHELMINTIC DRUG IN HELMINTHS AND ITS HOSTS Diseases caused by helminths, called helminthoses, are one of the most serious problems in veterinary and human medicine. These diseases are treated by anthelmintics but their effectiveness is often not sufficient due to resistance of helminths against common anthelmintics. The global anthelmintic resistance encouraged the developing of new drugs with a different mode of action. Monepantel (MOP) belongs to a new class of anthelmintic drugs known as amino- acetonitrile derivatives (AADs) that act on the nicotinic acetylcholine receptors. In 2011, MOP was approved for the treatment of gastrointestinal diseases caused by nematodes in the veterinary practice in the Czech Republic. It is produced commercially under the trade name Zolvix® (Novartis AG). The aim of this doctoral thesis was to study metabolism and effects of MOP and other AADs in order to contribute to the global research in this field. For this purpose, adults nematodes Haemonchus contortus (the sensitive strain ISE and the resistant strain WR) and its hosts Ovis...
METABOLISM AND EFFECTS OF NEW ANTHELMINTIC DRUG IN HELMINTHS AND ITS HOSTS
Stuchlíková, Lucie ; Skálová, Lenka (advisor) ; Kučera, Radim (referee) ; Machala, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Lucie STUCHLÍKOVÁ Supervisor prof. RNDr. Lenka SKÁLOVÁ, Ph.D. Title of Doctoral Thesis METABOLISM AND EFFECTS OF NEW ANTHELMINTIC DRUG IN HELMINTHS AND ITS HOSTS Diseases caused by helminths, called helminthoses, are one of the most serious problems in veterinary and human medicine. These diseases are treated by anthelmintics but their effectiveness is often not sufficient due to resistance of helminths against common anthelmintics. The global anthelmintic resistance encouraged the developing of new drugs with a different mode of action. Monepantel (MOP) belongs to a new class of anthelmintic drugs known as amino- acetonitrile derivatives (AADs) that act on the nicotinic acetylcholine receptors. In 2011, MOP was approved for the treatment of gastrointestinal diseases caused by nematodes in the veterinary practice in the Czech Republic. It is produced commercially under the trade name Zolvix® (Novartis AG). The aim of this doctoral thesis was to study metabolism and effects of MOP and other AADs in order to contribute to the global research in this field. For this purpose, adults nematodes Haemonchus contortus (the sensitive strain ISE and the resistant strain WR) and its hosts Ovis...
An acellular genotoxicity assay of complex mixtures of organic compounds bound on size segregated aerosols.
Fikejzlová, Monika ; Rössner, Pavel (advisor) ; Machala, Miroslav (referee)
The main aim of this work was to compare the genotoxicity of organic extracts from different size fractions of aerosol particles (1-10 µm, 0,5-1 µm, 0,17-0,5 µm) collected by high volume cascade impactors in various localities of the Czech Republic differing in the extent of the environmental pollution (Březno - strip mine, Dobré Štěstí - highway, Praha - city center, Láz - background station). Genotoxicity was determined in acellular assay of calf thymus DNA (CT-DNA) with and without S9 metabolic activation by analysis of DNA adducts induced by extractable organic matter (EOM) from the particulate matter (PM) by 32 P-postlabeling and the ability of extracts to induce oxidative DNA damage was evaluated using the competitive ELISA test. The main finding of this work is that most of the observed genotoxicity is connected with fine particles (<1 µm). The concentration of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) in EOMs indicate that fine fractions bound the highest amount of c-PAHs in all sampling sites. This fact might be related to a higher specific surface of this fraction as compared with a course fraction and a higher mass as compared with a condensational fraction. As for aerosol mass, both fine and condensational fractions are effective carriers of c-PAHs. Similarly, the DNA...
Biotransformation and Transport of Xenobiotics in Helminths
Bártíková, Hana ; Szotáková, Barbora (advisor) ; Horák, Petr (referee) ; Machala, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Department of Biochemical Sciences Candidate Mgr. Hana Bártíková Supervisor Doc. Ing. Barbora Szotáková, Ph.D. Title of Doctoral Thesis Biotransformation and transport of xenobiotics in helminths Infectious diseases caused by parasitic helminths are a major problem threatening health of domestic and wild animals and affecting agricultural industry worldwide. Treatment of helminthoses is based on administration of anthelmintic drugs, with benzimidazoles being the most important group. Unfortunately, the irrational use of similar anthelmintics has led to the development of drug resistance in helminths, thus causing a serious problem in the veterinary practice. Possible mechanisms of drug resistance development include changes of pharmacokinetic processes (changes in drug transport or increased drug deactivation), which are based on an increased activity of biotransformation enzymes and transporters in helminths. Understanding the mechanisms of drug resistance and defence strategies of parasites against drugs can prolong the efficacy of current anthelmintics and help to find new strategies for the control of helminthoses. Although drug metabolizing enzymes and transporters of helminths serve as an efficient defence...
Regulation of Human Carbonyl Reductase 3 (CBR3) Expression
Malátková, Petra ; Wsól, Vladimír (advisor) ; Pávek, Petr (referee) ; Machala, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Petra Malátková Supervisor Prof. Ing. Vladimír Wsól, Ph.D. Title of Doctoral Thesis Regulation of Human Carbonyl Reductase 3 (CBR3) Expression The regulation of human carbonyl reductase 3 (CBR3) expression has been complete mystery until recently and is still not well understood. Because the transcriptional regulation of a gene is closely related to the function of encoded protein, the elucidation of the regulation of CBR3 might help to understand its physiological role which has not been elucidated up to the present. The promoter of CBR3 has been described in 2009. The CBR3 promoter contains several putative binding sites for various transcription factors. In 2010, we have shown that CBR3 is regulated via the Nrf2/ARE signaling pathway. This was the first study about the transcriptional regulation of CBR3. The involvement of Nrf2 in the regulation of CBR3 has been recently confirmed by another research group. The functional antioxidant response element (ARE) is located at 2698 bp upstream of the translation initiation codon of CBR3 (−2698ARE). However, the analysis of CBR3 promoter encompassing 2500 bp indicated the presence of cis regulatory upstream element in sequence between...
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...
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...
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...

National Repository of Grey Literature : 13 records found   1 - 10next  jump to record:
See also: similar author names
2 Machala, M.
3 Machala, Marek
12 Machala, Martin
2 Machala, Michal
Interested in being notified about new results for this query?
Subscribe to the RSS feed.