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Mechanisms of metronidazole resistance in bacteria and anaerobic eukaryotes
Pilařová, Kateřina ; Kulda, Jaroslav (referee) ; Hrdý, Ivan (advisor)
This bachelor thesis tries to describe mechanisms of resistance in different groups of organisms, where metronidazole is used for treatment. These organisms are bacteria (genus Bacteroides, Helicobacter, Clostridium) as well as anaerobic eukaryota (genus Trichomonas, Tritrichomonas, Entamoeba, Giardia). It is important, that metronidazole acts selectively only on cells living in anaerobic or microaerophilic environments. Metronidazole enters the cell by passive diffusion and is subsequently reduced to cytotoxic intermediate which damages the cell at different levels. Metronidazole can also enter the cell with aerobic metabolism, also the reduction can occur, but the eventual radical is then thanks to oxygen transformed back to metronidazole in the process called futile cycling. Oxygen then forms superoxide, O2-. Organisms with aerobic or microaerophilic metabolism cannot detoxify nitroradical with oxygen, so they developed other ways how they protect themselves against the harmful effects of nitroradicals. Sensitivity of these patogens to metronidazole correlates with the changes of their enzymatic constitution. Perhaps the most basic mechanism how the patogens combat metronidazole is the prevention of reduction of the drug. The way how the organisms prevent reduction differs between species. There is a...
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Correlation of morphologic and moleculargenetic features of selected tumors
Šíma, Radek ; Skálová, Alena (advisor) ; Boudová, Ludmila (referee) ; Ehrmann, Jiří (referee)
We present a series of 16 salivary gland tumors with histomorphological and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma and low grade cystadenocarcinoma, as well as displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for PAS, mucicarmine, MUC1, MUC4 and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21-75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged...
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Biochemická a funkční charakterizace nového transmembránového adaptorového proteinu NVL
Vonková, Ivana ; Černý, Jan (referee) ; Brdička, Tomáš (advisor)
In T cells, signalling events initiated at the immunological synapse by T cell receptor (TCR) have been already thoroughly studied. In contrast, signalling pathways involved in MHCII-mediated signal transduction on the APC side of this structure are still rather poorly understood. Transmembrane adaptor proteins (TRAPs) are a class of proteins with an essential role in signalling triggered by TCR and other immunoreceptors. So far no TRAPs involved in MHCII signalling have been identified. In this work a new TRAP, highly enriched in the immunological synapse in APCs is described and termed Nvl. Nvl is expressed exclusively in professional antigen presenting cells - B cells, monocytes/macrophages and dendritic cells, and the level of its expression positively correlates with the expression of MHCII. Nvl is present in tetraspanin microdomains and together with tetraspanins it is localized to the polarized structures of the cell, including uropod, cleavage furrow, and, most interestingly, the immunological synapse. The presence in the immunological synapse indicates possible role for Nvl in MHCII- mediated signal transduction. Indeed, Nvl becomes tyrosine-phosphorylated after stimulation via MHCII, although strong phosphorylation has also been observed after FcγR stimulation or treatment with...
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Interakce umělé fotosyntetické antény s akceptory elektronů
Dostál, Jakub ; Pšenčík, Jakub (advisor) ; Fejfar, Antonín (referee)
The use of bacteriochlorophyll aggregates as a sensitizer for dye-sensitized cell has been studied in this work. Bacteriochlorophyll aggregates exhibit unique light-harvesting properties combining high optical density, long-term stability and exciton delocalization. Preparation of the GrÄatzel type photovoltaic cells has been successfully managed during this research. The cells were sensitized by bacteriochlorophyll c both in monomeric and aggregated form, and were characterized by measuring photoinduced current, voltage and other properties. As a part of this work a theoretical model of reversible two-level photovoltaic cell was derived from the thermodynamic principles. Predictions of this model are compared with experimental data and with published results.
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Clinical and pathologic correlation of complications of intensively treated hemato-oncological patients with a targeted focus to the involvement of the oral cavity and rare case of secondary neoplasia.
Vokurka, Samuel ; Boudová, Ludmila (advisor) ; Chlumská, Alena (referee) ; Faber, Edgar (referee)
Summary: In this thesis section "Oral Mucositis (OM) and oral Graft versus Host Disease (GVHD) in patients after allogeneic stem cells transplantation and with focus to FLU/MEL conditioning regimen" the author deals with following issues: 1. Literature overview: The overall negative impact of OM is mentioned and the complex pathogenesis, clinical characteristics, incidence and factors influencing both OM and GVHD are described. The histological features of GVHD and classification of it are mentioned, too. Conventional and reducedintensity conditioning transplant regimens, including FLU/MEL are presented. 2. Methodological section: Prospective observational study of 117 patients after allogeneic stem cells transplantation with BU/CY2/±ATG (26%), FLU/MEL (60%), FLU/CY (9%), Bu/FLU/ATG (2%) and HD-CY/ATG (2%) conditioning regimens. OM assed according to WHO criteria, GVHD assessed according to NIH criteria accepted by the EBMT. The statistical univariate analysis performed by means of GraphPad In Stat - Statistica Software (Man- Whitney, Fisher, t-test), p<0,05 considered significant. Multivariate analysis used in OM risk factors assessment. 3. Results: The OM incidence was significantly dependent on pre-transplant conditioning regimen (Bu/CY2/±ATG: 100%, FLU/MEL: 78%, FLU/CY: 9%, p=0,0001) in multivariable...
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Metabolomic analysis of plasma samples using ultra performance liquid chromatography and high resolution mass spectrometry
Machová, Karolína ; Solich, Petr (advisor) ; Kujovská Krčmová, Lenka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Karolína Machová Consultant: Prof. RNDr. Petr Solich, CSc. Diploma Thesis Title: Metabolomic analysis of plasma samples using ultra performance liquid chromatography and high resolution mass spectrometry Metabolomics is a novel type of science which represents a complex methods of metabolite determination in biofluid e.g. plasma, urine, saliva, cerebrospinal fluid and sperm. The method describes cell mechanisms and finds wide assertion in disease diagnostics, biomarkers description, disease, pathophysiology and in clinical practice. It is vital to have a sensitive method because levels of metabolites are quite low. Metabolomic analysis uses mainly high-performance liquid chromatography combined with mass spectrometry for detection. However, other methods such as nuclear magnetic resonance spectroscopy and gas chromatography can also be used. Presented work is mainly focused on method standardization for identifying metabolites in clinical practice with the use of ultra-performance liquid chromatography and mass spectrometry. The primary outcome was to establish searching parameters for the operating software to automatically identify xenobiotics in provided sample and compare them with...
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The effect of histone deacetylase inhibitor vaplroate on activity and expression of cytochromes P450 and peroxidases oxidizing ellipticine
Göttlicherová, Markéta ; Souček, Pavel (referee) ; Stiborová, Marie (advisor)
Ellipticine is a potent antineoplastic agent, whose mode of action is considered to be based mainly on DNA intercalation and inhibition of topoisomerase II. Ellipticine was also found to form covalent DNA adducts mediated by its enzymatic activation with cytochromes P450 (CYP) and peroxidases. The next study demonstrated increasing formation of these ellipticine-DNA adducts by histone deacetylase inhibitor valproate (VPA) in neuroblastoma cells. This phenomenon correlates with increasing cytotoxicity of ellipticine induced by this histone deacetylase inhibitor. This observation can be explained by several mechanisms. One of them can be loosening the structure of chromatine, which leads to accessing DNA for modification. Another one is the effect of VPA on activities and expression of enzymes metabolizing ellipticine. This study was aimed to test the second hypothesis. Since VPA has been shown to be metabolized by similar enzymes as ellipticine is, we have studied the effect of VPA (i) on oxidation of ellipticine by cytochromes P450 and peroxidases, (ii) on activities of the CYP enzymes, which significantly participate in oxidation of ellipticine (CYP1A, CYP3A) and (iii) on expression of enzymes oxidizing ellipticine (CYP1A1, CYP3A4, lactoperoxidase). Oxidation of ellipticine in vitro by model...
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Diagnostic morphological features of PDGFRA-mutated gastrointestinal
Daum, Ondřej ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Ehrmann, Jiří (referee) ; Zámečník, Josef (referee)
Daum O., Grossmann P., Vanecek T., Sima R., Mukensnabl P., Michal M. (2006): Diagnostic morphological features of PDGFRA-mutated gastrointestinal stromal tumors: Molecular genetic and histological analysis of 60 cases of gastric GISTs. Ann. Diagn. Pathol. In Press Summary In this study, 60 gastrointestinal stromal tumors (GISTs) of the stomach were analyzed to elucidate the possible relation of their morphology to mutation status of KIT and PDGFRA genes. The patients included 27 men and 33 women with a mean age of 63,8 years (range 12 to 92). Only one tumor occurred before the age of 21 years. KIT mutations were detected in 31 cases (51,7%), PDGFRA mutations in 22 cases (36,7%), and seven cases (11,7%) were KIT and PDGFRA wild type. When the mutation status was correlated with histological features of the tumors, epithelioid or mixed epithelioid/spindle cell pattern and mast cell infiltration were found as the most reliable signs of PDGFRA mutation. Neoplastic rhabdoid cells and multinucleated giant cells, also previously reported as features of PDGFRA mutated GISTs, seemed to be less specific but still helpful markers in our study. Finally, tumor infiltrating lymphocytes and myxoid stroma do not seem to be valuable histological signs. Daum O., Klecka J., Ferda J., Treska V., Vanecek T., Sima R., Mukensnabl...
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The role of transport systems for potassium cations in the physiology of Saccharomyces cerevisiae yeast
Marešová, Lydie ; Sychrová, Hana (advisor) ; Pácha, Jiří (referee) ; Janderová, Blanka (referee)
[n this work, we present the characteristics of kha 1 6,. strains in the background of various multiple mutations in genes encoding alkali-metal-cation transporters. Two main phenotype manifestations of the khal deletion were growth defect on high externa\ pH and hygromycin sensitivity. The correlation between these phenotypes and the kha 1 deletion was confirmed by plasmid complementation. Fluorescence microscopy of GFP-tagged Kha 1 p showed that this antiporter is localized preferentially intracellu\arly (in contrast to the plasma-membrane Na+/H+ antiporter Nha 1 p). Based on these findings, Kha 1 p is probably not localized in plasma membrane and do es not mediate efflux of alkali metal cations from cells (as published before in RammÍrez el aJ., 1998), but is important for the regulation of intracelular cation homeostasis and optima\ pH contro l, similarly as the Nhx l p. The khal deletion phenotypes were complemented by heterologous expression of a plant antiporter AtChx 17, showing that the proteins AfChx 17 and SeKhal could have similar ťunction and that S cerevisiae khal deletion mutants could serve for heterologous expression and characterization of some plant transporters in yeast, especially those localized intracellularly. We also showed that the presence of the Tokl channel strongly infl uences...
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Příprava a charakterizace tenkých vrstev oxidů zirkonu a titanu
Krejčíková, Simona ; Matějová, Lenka ; Matěj, Z. ; Jirkovský, Jaromír ; Šolcová, Olga
Titania and zirconia belong to nanoporous materials with huge application potential in photocatalysis, dye-sensitized photoelectrochemical cells, electrochromic devices, sensors and other applications, especially in the form of nanolayers. Differences in surface morfology, texture and crystallinity influence their catalytic impact. Therefore special attention is focused on the detailed textural and structural characterizations of thin titania-zirconia nanolayers prepared by sol-gel templated route.
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