National Repository of Grey Literature 135 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Characterization of flubendazol reduction in human in vitro
Štěpánková, Jana ; Szotáková, Barbora (advisor) ; Novotná, Eva (referee)
ASBSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Jana Štěpánková Supervisor: Prof. Ing. Barbora Szotáková, Ph.D. Title of Thesis: Characterization of flubendazol reduction in human in vitro Flubendazole (FLU) is an anthelmintic of the benzimidazole type used as a treatment or prophylaxis of helminthoses in livestock and wild animals. FLU is also registered for the treatment of parasitic diseases caused by intestinal nematodes in humans. Its mechanism of action lies in its specific binding to tubulin, which disrupts the structure and function of microtubules for the therapy of parasitosis in humans. The advantage of this drug is also the low systemic toxicity. That is why the anticancer activity of FLU is now under study. The aim of this rigorous work was to characterize the reduction of FLU in human liver subcellular fractions as this information is still lacking in available literature. Stereospecificity, subcellular localization, preference of coenzymes, enzyme kinetics of FLU reduction, and activity of enzymes involved in FLU reduction were studied in this project. Measurement results have shown that FLU is predominantly reduced in cytosol and nicotinamide adenine dinucleotide phosphate reduced (NADPH) coenzyme is preferred. FLU...
Czech Housing Construction 1958-1970
Novotná, Eva ; Švácha, Rostislav (advisor) ; Moravčíková, Henrieta (referee) ; Spurný, Matěj (referee)
The presented dissertation concerns selected topics on flat construction in the 60's - experiments and prefabricated housing estates - and examines them closely in four different layers - political, ideological, architectonic and social. The work is structured into four main chapters, which constitute four pillars to uncover the history of flat construction and its context. The initial hypothesis of the dissertation was that the birth of panel housing estates at the end of the 50's, as well as its form and content in the upcoming decade, was influenced by the different starting points of the four mentioned layers. The viewpoint of state socialism and its ideology stemmed from the situation, when architecture in the whole socialistic block seized to be the instrument of Stalinist political representation in the spirit of the socialist realism and it became an important instrument of social reform on the promoted path to communism. This opinion, projected on an economic level, lead to an assumption that an affordable and high-quality collective housing makes the society effectively economically modernized. The living in these housing estates was intended to become the "display window" of the socialist lifestyle as well as the means of a morally higher type of consumer society. In the atmosphere of...
Comparison of development and current state of the library of Geology Faculty of the Charles University in Prague and the CADIST Geosciences et Environment library in Paris
Molíková, Barbora ; Papík, Richard (advisor) ; Novotná, Eva (referee)
The aim of the thesis is to compare the historical development and current state of the Library of Geology at Faculty of Natural Sciences, Charles University in Prague and the CADIST Géosciences et Environnement library in Paris. In the Introduction, the development of both libraries, including historical contexts, is documented. In the second part of the thesis, the decomposition method of library systems is used to analyse the current state of both libraries. Data for the analysis was collected by the author, partly during her employment in the Library of Geology at the Charles University in Prague, and partly during the internship at the CADIST Géosciences et Environnement Library in Paris. In the third part, the comparison based on the comparative librarianship method, of both geological libraries is created. Consequently, the possibilities of innovation of the Library of Geology at the Charles University in Prague inspired by the CADIST Géosciences et Environnement Library in Paris, and the possibilities of future cooperation among branch-related libraries are proposed. Finally, the benefits of the work are assessed.
Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes
Šmídlová, Monika ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical sciences Candidate: Bc. Monika Šmídlová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes Key words: reductases, leukemia, cytostatics, inhibition Anthracycline antibiotics, especially daunorubicin, are widely used for the treatment of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Although the efficacy of these drugs is high, treatment is still limited due to cardiotoxicity and tumor cell resistance to anthracyclines. Mechanisms that contribute to the formation of anthracycline resistance include metabolic biotransformation (reduction) to less efficient secondary alcohols. The reduction is calatyzed by carbonyl reducing enzymes belonging to aldo-keto reductase (AKR) and short chain dehydrogenase/reductase (SDR) superfamilies. The discovery of AKR and SDR inhibitors could help to overcome anthracycline resistance and also reduce cardiotoxicity caused by these drugs. The aim of the diploma thesis was to find out whether all-trans-retinoic acid, cyclophosphamide, cytarabine, cladribine and prednisolone are able to inhibit anthracycline reductases AKR1A1, AKR1B10, AKR1C3, AKR7A2...
The effect of lipid signaling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells
Sagandykova, Aigul ; Čečková, Martina (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aigul Sagandykova Supervisor: PharmDr. Martina Čečková, Ph.D. Consultant: Dr. Mikko Gynther Ph.D. Title of diploma thesis: The effect of lipid signalling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells. Nowadays cancer remains one of the most challenging health issues worldwide. Chemotherapy represents one of the essential approaches in the treatment of malignant diseases. However, multidrug resistance (MDR), a multifactorial phenomenon described as a loss of sensitivity of cancer cells to several diverse chemotherapeutic agents at the same time, often compromises the therapy outcomes. A well-known cause of MDR is an increased expression or/and an enhanced activity of efflux drug transporters of ATP binding cassette (ABC) superfamily, which has been found in many types of cancer. In the last decade, an expanding body of literature suggested a new hallmark of cancer cells - inflammation. An inflammatory microenvironment potentiates tumorigenesis and upregulation of transporters. Moreover, several observations show that ABC transporters mediate the transport of some signalling lipids. This new insight provided...
Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines.
Kouklíková, Etela ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Etela Kouklíková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines Cyclin-dependent kinase inhibitors (CDKi) are considered as a suitable treatment especially in patients with wrong prognosis or advanced stage of cancer. It has only recently been discovered that CDKi are able to influence the activity of some enzymes from aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase (SDR) superfamilies. AKR and SDR enzymes belong to a group of carbonyl reducing enzymes that are involved in the metabolism of endobiotics and xenobiotics. An important group of drugs that are metabolized by these enzymes to less efficient compounds are anthracyclines. The aim of this diploma thesis was to find out whether purvalanol A, roscovitin, dinaciclib, AZD5438 and R547 can affect the expression of the most important anthracycline reductases (AKR1A1, AKR1B10, AKR1C3, AKR7A2 and CBR1) in human HepG2 and HL-60 cell lines. Expression of anthracycline reductases in cells exposed to CDKi was evaluated at mRNA level by RT-qPCR and at protein level by Western blotting. The...
Study of protein-protein interaction of DHRS7 enzyme by pull-down assay
Káchová, Kateřina ; Novotná, Eva (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biochemical Sciences Candidate: Kateřina Káchová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of protein-protein interaction of DHRS7 enzyme by pull-down assay Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one of the less studied enzymes of SDR superfamily. It has been proven that this enzyme is in vitro involved in reductive metabolism of various compounds, such as steroids, retinoids and xenobiotics. Recently results pointing out to possible role of this enzyme in the pathogenesis of prostate cancer or other diseases has been published. It would be suitable to better characterize this enzyme to clarifying its patho/physiological role in the organism. Because protein-protein interactions seem to be important for the function of proteins, the aim of this study was to identify interaction partners of the DHRS7, and thus contribute to the improvement of understanding of this enzyme. For our experiments, pull-down assay, in vitro method was utilized. The first step was immobilization of DHRS7 enzyme (bait protein) to suitable carrier (His Mag Sepharose Ni particles and nonmagnetic Protino Ni-IDA particles). Subsequently, the carrier with immobilized DHRS7 was incubated with the lysate of Hep G2...
Purification of membrane bound enzyme DHRS7B
Mariničová, Valéria ; Novotná, Eva (advisor) ; Szotáková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Valéria Mariničová Supervisor: RNDr. Eva Novotná , Ph.D. Title of diploma thesis: The purification of the membrane-bound enzyme DHRS7B The membrane-bound DHRS7B enzyme, from the SDR (short-chain dehydrogenase/reductase) superfamily, is one of poorly characterized protein of the human organism. Despite the lack of information about its properties, it was observed in mice, where it is named to as PexRap, localized in peroxisomes. It is a peroxisomal reducing protein that uses NADPH as a cofactor. Its participates in biosynthesis of peroxisomal ether lipids during adipogenesis in mice. The role of human DHRS7B in cells or evantually in diseases has been only speculated and therefore it is in the focus of research. The aim of this work was to obtain the pure recombinant human DHRS7B enzyme prepared in Sf9 cells. It is a membrane protein, so it was necessary to find a suitable detergent that is able to remove the DHRS7B enzyme from the phospholipid membrane while preserving its activity. The most suitable detergent was DDM 1:1 (w/w) protein:detergent. Further step was its purification by affinity chromatography, the pure DHRS7B protein with a ketotifen reducing activity of 62 nmol/mg/min was obtained....
Study of resistance in cancer therapy - protein kinase inhibitors influence on activity of selected human reductases II.
Flaxová, Michaela ; Wsól, Vladimír (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Michaela Flaxová Supervisor: prof. Ing. Vladimír Wsól, Ph.D. Title of diploma thesis: Study of resistance in cancer therapy - protein kinase inhibitors influence on activity of selected human reductases II. Nowadays cancerous diseases are significant problem, and the incidence is still increasing. Anthracycline antibiotics are important in therapy of cancerous diseases, unfortunately, they have serious side effects and drug resistance is often obstacle for the effective treatment. The origin of cardiotoxicity is still not clear, older theories were based on formation of reactive oxygen species (ROS). Nevertheless, newer theories confirm that anthracyclines or their metabolites influence complicated cell pathways. The enzymes, which metabolize anthracyclines, specifically daunorubicin, were the subject of this work. The carbonyl reducing enzymes are NADP(H)-dependent oxidoreductases, which are able to catalyse reduction of aldehydes and ketones to primary and secondary metabolites, daunorubicin is transformed to daunorubicinol directly by this way. Therefore we are most interested in enzymes from aldo-keto reductase family and short-chain dehydrogenases (SDR), namely AKR1C3 and CBR1. Many enzymes...
Effect of anthelmintics on expression of selected plant enzymes
Navrátilová, Martina ; Matoušková, Petra (advisor) ; Novotná, Eva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Martina Navrátilová Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Effect of anthelmintics on expression of selected plants enzymes Fenbendazole (FEN) is a broad-spectrum benzimidazole anthelmintic that is widely used to prevent and treat helminthoses in farm animals. The use of anthelmintics is associated with the risk of their transfer to the environment, where they can potentially affect non-target organisms, including plants. They come into contact with anthelmintics and their metabolites mainly due to the fertilization of farmland with manure and/or come directly into contact with the excrements of treated animals on pastures. There have not been many studies focused on the cell physiology and cell metabolism of plants affected by anthelmintics, which lead to our participation in a study which dealt, in part, with the influence of FEN on the transcriptome and gene expression in model plant Arabidopsis thaliana. A. thaliana is a monocotyledonous plant, which is a very common model organism of higher plants. Its genome was also published in 2000, allowing extensive research into gene expression. The aim of this work was to monitor expression of selected A....

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