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Analytical Evaluation of Drugs and Drug Candidates from the Group of Iron Chelating Agents
Stariat, Ján ; Klimeš, Jiří (advisor) ; Šatínský, Dalibor (referee) ; Šišpera, Luděk (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Ján Stariat Supervisor Prof. RNDr. Jiří Klimeš, CSc. Title of Doctoral Thesis Analytical evaluation of drugs and drug candidates from the group of iron chelating agents High performance liquid chromatography (HPLC) ranks among the most important analytical techniques in the field of pharmaceutical analysis thanks to its robustness and the ability to separate and qualitatively and quantitatively analyse the compounds presented in various samples. The ongoing progress in the development of novel stationary phases and detection techniques allows rapid analysis and to get comprehensive characterization of the analytes presented in the complex samples even at very low concentrations. Cancer still remains a leading cause of death, thus the need for novel, efficient treatment strategies is of crucial importance. The mechanism based on iron chelation (Fe) inside the tumour cells represents one of the most promising strategy which could enhance the prognosis of patients suffering from cancer resistant to standard chemotherapy. Thiosemicarbazone iron chelators are currently under intensive development as novel anticancer drugs. Their strong antiproliferative...
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Panels of steroid receptor reporter cell lines for compound profiling and development of selective ligands for estrogen receptor alpha and beta
Sedlák, David ; Bartůněk, Petr (advisor) ; Anzenbacher, Pavel (referee) ; Kasal, Alexander (referee)
of the Ph.D. thesis Steroid hormone receptors represent a major target in the drug discovery. As ligand inducible transcription factors, their activity can be modulated by small lipophilic molecules. The first part of this work describes a preparation of two panels of potent, selective and robust luciferase reporter cell lines on the unified cellular background in U2OS osteosarcoma cell line. This system consists of two panels of stable luciferase reporter cell lines for estrogen receptor α (ERα), estrogen receptor β (ERβ), androgen receptor (AR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and progesterone receptor (PR). The first panel of reporter cell lines relies on the expression of the chimeric steroid receptors created by the replacement of the N-terminal part of the steroid receptor molecule by Gal4 DNA binding domain (Gal4 DBD) binding to 9 copies of Gal4 upstream activation sequences (Gal4 UAS) in the promoter of the pGL4 luciferase reporter vector. In the second panel of reporter cell lines the activation of either synthetic promoter containing multiple hormone response elements or viral promoter derived from MMTV LTR is mediated by full- length exogenously expressed steroid receptors. We have extensively validated both panels using 28 well established ligands, carefully...
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Vliv stavu a funkce imunitního systému na pohlavní výběr u ptáků
Vinkler, Michal ; Albrecht, Tomáš (advisor) ; Kleven, Oddmund (referee) ; Grim, Tomáš (referee)
Evolution is a most fascinating feature of all living things in our world. The means of organismal evolution are diverse, comprising mainly of natural and sexual selection. Both of these phenomena may contribute to evolutionary adaptations in health and disease. The questions of immunity impact on the process of sexual selection and sexual selection for increased anti-parasite resistance are wide issues of the present research in natural sciences. Their clarification requires multidisciplinarily-based investigation combining a variety of partial results into a single united paradigm. My co-workers and I have chosen several specific issues to study, in order to fill some of the important gaps of the current knowledge. We proposed the Carotenoid maintenance handicap hypothesis to point out that optimisation instead of maximisation of the carotenoid intake and ornamental display may be physiologically convenient for the individual. In Scarlet rosefinch (Carpodacus erythrinus) we confirmed the role of the carotenoid-based ornamental colouration in the process of sexual selection and investigated several partial aspects of the association between immunogenetics, immune function, health and the ornament expression and mate choice. In Zebra finch (Taeniopygia guttata) we have shown that the present way of...
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Sulfation and desulfation of neuroactive steroids in normal and neoplastic primate brain tissues
Kříž, Lubomír ; Hampl, Richard (advisor) ; Lapčík, Oldřich (referee) ; Pácha, Jiří (referee)
A novel methodology for the determination of steroid sulfatase (STS) and sulfotransferase (SULT) activities in primate brain tissue have been developed and evaluated. STS activity determination was based on enzyme assay followed by liquid-liquid extraction ofthe reaction product, its subsequent derivatization and gas chromatography-mass spectrometry analysis. Indirect determination including product hydrolysis and determination by radioimmunoassay was used for assessment of SULT activity. For both, STS and SULT assays, optimal reaction conditions were found while strong structure-activity relationships for both enzyme activities were observed. Additionally, so far unidentified high-substrate inhibition for STS was revealed wíth a hypothesis suggesting its physiotogícal relevance' Determinations of STS and SULT activities in monkey brain regions revealed differences between genders and brain regions. Due to low number of samples, significance was not described. For STS kinetic characteristics were determined. In human brain tumors, STS and SULT activities showed highly significant differences according to diagnoses. Furthermore, tendency to cluster formation with respect to both enzyme activities emerged. It indicated specific metabolic characteristics especially for glioblastomas considered as the...
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The role of infectious diseases in the development and progression of renal graft dysfunction
Drenko, Petr ; Reischig, Tomáš (advisor) ; Hrabák, Jaroslav (referee) ; Dedinská, Ivana (referee)
Infectious diseases and their impact on the development and progression of renal graft dysfunction Infectious diseases represent a significant risk factor for morbidity and mortality among organ transplant recipients. In renal transplant recipients, infectious complications are the most common cause of death with preserved graft function. Cytomegalovirus (CMV) infection is one of the most common opportunistic infections after solid organ transplantation. Despite the routine use of modern preventive measures, CMV infection puts kidney transplant recipients at higher risk of graft failure and mortality. In addition to direct action, CMV also has an immunomodulatory ability that is associated with an increased risk of T-lymphocyte-mediated and possibly antibody-mediated graft rejection in particular, both of which limit long-term allograft survival. The two main strategies for CMV prevention include (1) universal prophylaxis with treatment of all patients at risk (according to donor-recipient serostatus) with antiviral drugs and (2) preventive therapy based on CMV monitoring and treatment of only selected patients with significant viral replication (DNAemia). The current International Consensus Guidlines consider both strategies equivalent in patients after kidney transplantation, even in the high- risk...
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Magical Realism in Persian and Saudi Narrative Writing
Vojtíšková, Věra ; Ondráš, František (advisor) ; Nováková, Soňa (referee) ; Lišková, Iva (referee)
The dissertation Magical Realism in Persian and Saudi Narrative Writing views as essential the assumption that the phenomenon of magical realism is not restricted solely to the cultures with colonial legacy, but is transferable to literary works created under systematic and systemic violence anywhere in the world. Previous research of the dissertation's author proved the existence of parallels in the dynamics of sociopolitical development of Iran and Saudi Arabia in the 20th century, foremost in the power relation of the states to their citizens and in the status of women in the society, while there was a strong tendency towards institutionalization of the traditional patriarchal, androcentric and misogynic societal paradigms since the second half of the 20th century. In the last thirty years, women have countered this situation through increased literary activity that has turned out to be an important means of self-fulfillment and emancipation. The fact that some of the most significant Iranian and Saudi women writers use magical realism directed the research to examination of this concept's relevance for the Persian and Saudi narrative writing, inquiry into the reflection of the gender issues and their comparison in both literatures. A detailed case study of two works, each from one country, led...
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Concept of species in bears (Ursidae): practical, historical, and theoretical viewpoint
Wagner, Jan ; Fejfar, Oldřich (advisor) ; Sabol, Martin (referee) ; Musil, Rudolf (referee)
The present thesis surveys topic of taxonomic diversity and phylogeny of bears (Mammalia, Ursidae) and aspects of its contextual setting under effects of changing conceptual and methodological viewpoints. This problem is studied from several perspectives. The historical perspective is represented by a critical overview of the history of specific and infraspecific classification of bears with special respect to mutual influences of this classification and theoretical concepts of species accepted in particular periods. The perspective of material approach is exemplified by a material-based study of taxonomical and phyletic status of selected Pliocene to Middle Pleistocene ursine taxa. Along with deconstruction of some traditional hypotheses this produced a model explaining species diversification in ursine bears and its discussion in terms of factual relevance of included background concepts. In the pre-evolutionary period the bear species were usually understood broadly, as incipient immanent entities, yet exhibiting obvious certain infraspecific variability. This was established using definitions of varieties (mostly not identifiable with present subspecies or infraspecific taxa) considered as unstable modes of particular species. Although, in the post-Darwinian period, the concept and taxonomic...
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Imprints of history in post-agricultural forests
Vojta, Jaroslav ; Suchara, Ivan (advisor) ; Honnay, Olivier (referee) ; Tichý, Lubomír (referee)
IMPRINTS OF HISTORY IN POST-AGRICULTURAL FORESTS Ph.D. Thesis Jaroslav Vojta Charles University in Prague, Faculty of Science Praha, 2010 Promotor: Ivan Suchara List of original papers I. Relative importance of historical and natural factors influencing vegetation of secondary forests in abandoned villages (Jaroslav Vojta - Preslia 79: 223-244) II. Land use legacies in post-agricultural forests in the Doupovské Mountains, Czech Republic (Martin Kopecký & Jaroslav Vojta - Applied Vegetation Science 12: 251-260) III. Woody vegetation continuity, topography, and distance to ancient forests have complex effects on the vegetation and species richness of abandoned pastures (Lucie Drhovská & Jaroslav Vojta - submitted) 1 Introduction Land use changes have had a profound effect on vegetation cover. Often, succession results in the recovery of forests on former agricultural land. As areas of post-agricultural forests become increasingly prominent in landscapes of developed countries, these processes have attracted the attention of ecologists. Many questions have arisen regarding the possibility of restoring original forest communities on former agricultural lands (Flinn and Vellend, 2005; Hermy and Verheyen, 2007). At the same time, current and past land use changes could be seen as "natural experiments" that could...
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Behaviour and ecology of leopard geckos (Eublepharis macularius)
Jančúchová Lásková, Jitka ; Landová, Eva (advisor) ; Moravec, Jiří (referee) ; Sedláček, František (referee)
During evolution, the natural selection favours individuals with the best survival strategy and the highest reproductive success. From the evolutionary point of view, hybridization plays an important role in the process of speciation. Avoiding predators by choosing the most appropriate antipredator strategy increases the animal's chances of survival as well. Studying fitness consequences of hybridization and predation in Eublepharis macularius (Eublepharidae) was the main objective of this theses. Compared to other vertebrate groups, the reliable records on hybridization and its effect on the hybrid's fitness (fertility, survival) in lizards are scarce, despite their ability to hybridize between genetically distant species. These effects were examined in two species of eyelid geckos (E. macularius and E. angramainyu). We aimed to discover whether they were willing to hybridize with a heterospecific species and how the fitness of the hybrids would be affected. Similarly, were studied more genetically related forms of E. macularius species complex, the potential precopulatory barriers, and fitness cost of this hybridization. Analysis of published data has shown that the lizards hybridize between very phylogenetically distant species and are even "more successful" than birds or turtles. Surprisingly,...
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Social - pedagogical goals of community project concerning minorities
Foltýnková, Šárka ; Lorenzová, Jitka (advisor) ; Burešová, Karolína (referee)
AND KEY WORDS Social - pedagogical goals of community project concerning minorities Key words: Community, community work, community project, minority, social - pedagogical goals, semi-structured interview, field examine The theme of this thesis is community projects in the Czech Republic and their socio- pedagogical goals. The nature of work is theoretical work and research. In the theoretical part are defined basic concepts like community, community work, community project, minority and examples of organizations working with minorities through community projects. Research is based on semi-structured interviews within field examine, which introduces a view to Organisation Český západ, public participation in the implementation of community projects, what projects are highly relevant, to the skills acquired and in what situations seek the services of this organization in 2015. Their utterances are analyzed and interpreted in relation to individual objectives of this work. On the basis of this examine it was found that for informants was important to by employed. The conclusion summarizes the information from the interviews. Further value added of this thesis is the authentic assessment of direct participants in community projects and personal acquaintance with the opinion spectrum of the population...
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