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BCS (Biopharmaceutical information system) and in vitro/in vivo correlation of bioequivalent studies
Ćmiel, Radek ; Doležal, Pavel (referee) ; Tilšer, Ivan (advisor)
Biopharmaceutical classification system is a scientific framework for classifying a drug substance in to the groups based on its aqueous solubility and intestinal permeability. When combined with the in vitro dissolution characteristics of the drug product, then there are three major factors: solubility, intestinal permeability and dissolution rate. All these three factors correspond closely with the rate and extent of oral drug absorption from IR solid oral- dosage forms. This work presents the overview about the BCS from two major points of view, from the site of the World health organization (WHO) and U.S. Food and drug administration (FDA), while the FDA guideline for biowaiver is fully cited in Czech language. Also reflection of in vitro in vivo correlations in IR drugs development according to BCS is mentioned. Further, the thesis is analyzing the bioequivalence studies of Czech pharmaceutical company Zentiva, k. s. in context of BCS and compares the results with data obtained from the Canadian CRO Anapharm, which is a contract partner of many pharmaceutical companies being engaged in a clinical research and bioequivalence studies. Keywords: Biopharmaceutical classification system, solubility, permeability, dissolution, in vivo/in vitro correlations, Caco-2 cells, bioequivalence, IR drug...
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Biochemical properties of quaternary benzo(c)phenanthrene alkaloids
Přenosilová, Lenka ; Naiman, Karel (referee) ; Stiborová, Marie (advisor)
Quaternary benzo(c)phenanthridine alkaloids are plant products found in many plants. The richest sources are mainly Chelidonieae plants and the family Papaveraceae. The basis of the structure of quaternary benzo(c)phenanthridine alkaloids (sanguinarine, chelerythrine, sanguiluthine, sanguirubine, chelirubine, cheliluthine, macarpine) is N- methylbenzo(c)phenanthridine cation. Chemical structure of quaternary benzo(c)phenanthridine alkaloids related to their cytotoxic properties, the ability to intercalation into DNA and the fluorescence capabilities. Quaternary benzo(c)phenanthridine alkaloids occur in two forms, one of which operates reversible equilibrium depending on pH. Very important are the biological effects of quaternary benzo(c)phenanthridine alkaloids. These alkaloids could be used as fluorescent DNA probes and as supravital dye of nucleic acids. Individual quaternary benzo(c)phenanthridine alkaloids have many uses. Sanguinarine is used for its antiplaque and anti-inflammatory effects of oral hygiene. For its effect against the coagulation of blood platelets may play an important role in preventing cardiovascular diseases. Sanguinarine may be used as a potential cytostatic drug for the treatment of cancer. Chelerythrine is similar to use in oral hygiene products and is known for its...
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Vratislav Effenberger's poetry and its ideologic context
Caňko, Miloslav ; Vojvodík, Josef (advisor) ; Bílek, Petr (referee)
This study contains an analysis of the poetry of Vratislav Effenberger and the context of its ideas. The first two sections are devoted to the ideology of Czech surrealism, with which Effenberger is indelibly linked as a leading theoretician and which determined his direction for several long decades. The Introduction carries basic information about the history of Czech surrealism, the general problems of its theory and creative practice and the personality of the author in question. The following part examines in detail one aspect of the fundamental shift that occurred in Czech surrealism during its post-war developments: the shift from attempts at achieving a general disruption of the spirit (European rationalist thought), bringing about a total "crisis of consciousness," to mapping this crisis as a depressing problem of the contemporary world. This change is related to the different position of Czech surrealists regarding psychoanalysis: In this context, the author of this study refers to the two-member development scheme of Jean Michel Rabaté, according to which it is possible to distinguish between "hysterical" and "paranoid" discourse within surrealism, and proposes that it be supplemented by a third member - "analytical" discourse. The remaining sections of the whole study are focused on...
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Changes in selected characteristics of precipitation from convective and stratiform cloudiness
Rulfová, Zuzana ; Bednář, Jan (referee) ; Kyselý, Jan (advisor)
Significant trends in some characteristics of atmospheric precipitation have been observed in central Europe in recent decades. Little attention has been paid to the investigation whether these trends are related to changes of precipitation falling from v convective and stratiform cloudiness. This thesis deals with disaggregation of precipitation into convective and stratiform on the basis of the database of 10 SYNOP stations in the Czech Republic. The differentiated precipitation amounts were analyzed with respect to trends of total and heavy rainfall in individual seasons for the period 1982-2005. For convective precipitation in the western part of the Czech Republic, the observed trend is increasing in total precipitation, except for spring, and declining in heavy rainfall, except for fall and winter. In the eastern part of the Czech Republic, the total amounts are increasing (except for winter) and heavy rainfall is decreasing, except for spring. For stratiform precipitation, the growing trend prevails in all the characteristics of the total and heavy rainfall throughout the Czech Republic. The exception is the spring season with the downward trend.
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Building savings - legal and economic issues
Holečková, Eva ; Vondráčková, Pavlína (advisor) ; Novotný, Petr (referee)
LIII Závěr Zavedení stavebního spoření bylo nejúspěšnějším krokem bytové politiky v České republice po roce 1989. Hlavní přínos tohoto produktu spočívá v tom, že se jedná o způsob financování bytových potřeb, který je finančně dostupný širokým vrstvám obyvatelstva. Ač zpočátku bylo stavební spoření spíše institutem, jak výhodně uložit své volné finanční prostředky, stále více se stává nástrojem, jak získat vlastní střechu nad hlavou. Zvyšuje nejen zájem o výstavbu nových bytů a rodinných domů, ale také o provádění modernizací a rekonstrukcí, což je velmi důležité pro náš zastaralý bytový fond. Investice do bydlení, které stavební spoření podporuje, pozitivně ovlivní stavební výrobu a jak víme, vývoj stavební výroby je indikátorem pro vývoj ostatních sektorů ekonomiky. Pokud bude stavební výroba růst, dá se očekávat růst celé ekonomiky, a to je to, co si v době ekonomické krize všichni přejí. V současné době můžeme hovořit o velkém úspěchu stavebního spoření. Souvisí to s tím, že v době, kdy byl tento produkt uváděn na trh, sliboval nejen zajímavé výnosy, ale také stabilitu a bezpečné ukládání úspor. K oblíbenosti tohoto produktu přispěl také stát, který v rámci aktivní bytové politiky podpořil jeho rozvoj poskytováním optimální výše státní podpory. Významnou roli také sehrála skutečnost, že občané byli...
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Bridge formed by cell box girder
Zifčák, Karel ; Brtáň, Stanislav (referee) ; Nečas, Radim (advisor)
The subject of this thesis is the design and assessment of the bridge construction across the deep valley on highway traffic. From three variants, which were compared to each other, was the most suitable further examined. The solved structure is made of post-tensioned concrete, and is formed with cell box girder with transverse overhangs, which are supported by prefabricated struts over the length of the bridge. The load was considered by the European Standard EN 1991-2 - Traffic loads on bridges and dimensioning according to EN 1992-2-Design of concrete structures - Concrete bridges - Design and detailing rules.
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The individual and the social in the novel La casa grande
Obručová, Lucie ; Fousek, Michal (referee) ; Vydrová, Hedvika (advisor)
The focal point of this dissertation is the novel The Big House (La Casa Grande) by Álvaro Cepeda Samudio (1926 - 1972) a Colombian journalist,novelist, short storywriter, and filmmaker. Owing to the author' s personal literary development the dissertation pays shortly attention to his journalistic activities and further to his short story collection We Were Al! Waiting (Todos estábamos a la espera). In his novel he def1ects the town' s theme which is dominant one in his short stories and his novel emerges from his birthplace and its history. The subject is the historical event of the Ciénaga Massacre of striking journeymen from banana plantations. This is the backdrop to perform an individual drama, the one of a Colombian family whose inner problems ref1ect the whole society and acquire universal dimension. Above all, the analysis of the novel concentrates on the performance stage, individual characters who can be understood as archetypes, and on the time draft which necessitates repeating faults and mistakes. The fragmentary compositon of the novel correlates with the plurality of narrative perspectives and with the polyphonic narrative technique. The novel is to be understood knowing the background to the Colombian political life in the first half of the last century definied as bi-party system in its...
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In vitro evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of solid tumours.
Jedličková, Adéla ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradci Králové Department of Biochemical Sciences Candidate: Bc. Adéla Jedličková Supervisor: Mgr. Miloslav Macháček Title of diploma thesis: In vitro evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of solid tumors Nowadays, cancerous diseases belongs among the main causes of death, incidence continues to rise. Therefore research in the area of tumor treatment significantly focuses on the development of new potential anticancer drugs and therapeutical approaches. Photodynamic therapy (PDT) belongs to clinically approved therapeutic methods for the treatment of the malignant and nonmalignant diseases. PDT is composed of three main components - photosensitiser (PS), light and oxygen, all of them are non-toxic on their own. However, their interaction leads to a generation of highly reactive molecules. This method is based on absorption of light with appropriate wavelenght by PS and subsequent energy transfer from photon to surrounding molecules, especially to oxygen. This transfer leads to a generation of cytotoxic reactive oxygen species (ROS) of which singlet oxygen plays a main role. ROS subsequently causes a damage of surrounding cell structures, which leads to irreversible damage of cell functions and...
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Vnitrodruhová struktura Phytopthora alni Brasier et S. A. Kirk na území ČR
Černý, Karel
The work is aimed to study of morphological variability of Phytophthora alni complex in the area of the Czech Republic with use of numerical phenetics. The morphological analysis of 29 Phytophthora alni strains acquired from the area of the pathogen in the Czech Republic was carried out. In total there were studied 50 cultural and morphological characteristics: 14 cultural characteristics, 16 characteristics describing asexual and 20 characteristics describing sexual structures. The all morphological measurements were repeated twenty times at magnification 1600× with use of Olympus BH-2 microscope, Olympus E-510 camera and Quick Photocamera 2.3 measuring software. The data were processed in Statistica 8.0 in modules of non-parametric statistics, descriptive statistics, cluster analysis, analysis of principal components and discriminant analysis. In the area there was confirmed the presence of the two taxa belonging to the P. alni complex: Phytophthora alni subsp. alni (Paa) a Phytophthora alni subsp. uniformis (Pau). The third taxon (P. alni subsp. multiformis) was not found. The nominate subspecies Paa prevailed - more than 4/5 of studied isolates belonged to this taxon. The classification of isolates was in full agreement with molecular study of identical set of isolates which was parallely performed (Štěpánková et al. 2013). The morphological analysis showed, that majority of Czech isolates of P. alni complex can be successfully determined on the basis of standard morphological characters -- oogonial wall ornamentation, antheridial length, rate of aborted oogonia etc. Ca 10 % of isolates were found to be intermediate. All studied isolates were divided with series of cluster and PCA analysis in two relevant clusters and a discriminant function dividing the isolates in the two taxa on basis of morphological characters was generated and validated. The rate of standard oogonia, high of oogonial ornamentation, rate of two-celled antheridia with central septum and antheridial length were used as discriminators. The two different Paa morphotypes were found in the area of the Czech Republic. The discriminant function dividing the Paa isolates in these two morphotypes was also constructed and tested. The discriminators were oogonia diameter, high of oogonial ornamentation and width of antheridium. The most reliable character was the antheridial width: the north-western morphotype has antheridia wider by 3 micrometres than the south-eastern one. The Paa taxon was continuously distributed in the western part of the area, its frequency diminshes eastward. The distribution of the second taxon - Pau - was scattered and insular, but it was found out in the whole area of the Czech Republic. It could be supposed, that the parental taxon Pau had spread before Paa invasion in the area. Later the new and more combative Paa replaced the older weakly pathogenic Pau. The recent area of Pau is apparently insular and probably relict. The two Paa morphotypes importantly differ in their distribution - the first morphotype is more frequent in north-western part of the area (and predominates in western, central and northern Bohemia) while the second one is frequent in the south-eastern part (southern Bohemia and Moravia). Likely, these two subpopulations can represent the remains of colonisation waves of two allopatric Paa lineages. The lineages can originated by repeated independent hybridisation between parental Pau and Pam taxa somewhere in western or central Europe.
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The office spaces development in Prague after 1989
Císař, Milan ; Heřmanová, Eva (advisor) ; Sýkora, Luděk (referee)
In the nineties of the twentieth century the Prague office space market looked totally different from its current situation. The demand significantly exceeded the supply on the market and there was an entire lack of high-quality office places, which were built mostly in the city centre. There were predominating small projects of office and residential reconstructions which were limited by historical monument regulation and lack of space in the city centre. As of now the supply is prevailing on the Prague office space market and the situation for developers and tenants has totally changed. The competition of developers has rapidly increased and further increase is expectable. The development of new office buildings has moved from the city centre to the inner and outer city and the developers have focused on the multifunctional complexes, conversion of brownfields and construction of large city districts instead of separate office buildings. Prague office development is comparable with the development in Budapest and Warsaw. Commercialization of the city centre and suburbanization is even typical for all four capital cities in Central and Eastern Europe.
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