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Study of effects of antiretroviral drugs on transmembrane transport of tenofofovir disoproxil fumarate across MDCKII-ABCB1 cell monolayer
Repeľová, Beáta ; Červený, Lukáš (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Beáta Repeľová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of effects of antiretroviral drugs on transmembrane transport of tenofovir disoproxil fumarate across MDCKII - ABCB1 cell monolayer Tenofovir disoproxil fumarate (TDF) - ester prodrug of tenofovir is considered as one of the most frequently used component of combination antiretroviral therapy. Several ways of application and good patients' tolerability is typical for this compound. TDF is a substrate of dug transporter such as P-glycoprotein (P-gp) therefore its efflux activity may limit the bioavailability after oral administration and distribution of TDF. As many of antiretroviral drugs are also substrates or inhibitors of P-gp, drug - drug interactions with TDF at the level of transmembrane transport could be expected. The aim of the diploma thesis was to describe effects of co-administered antiretroviral drugs on transfer of TDF across MDCKII cell monolayer by using bidirectional transport and concentration equilibrium setups. The results of experiments confirmed that TDF is a substrate of P-gp. High values of efflux ratio describing transmembrane transport of TDF across parental cells have been observed. This...
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The news coverage of the HIV/AIDS issue in time (1996-2009)
Kvášová, Sabina ; Nečas, Vlastimil (advisor) ; Šoltys, Otakar (referee)
This Master thesis "HIV / AIDS in the czech newspapers in changing times (1996-2009)" discusses the media coverage of the topic of HIV / AIDS in the czech newspapers: MF Dnes, Blesk and Hospodářské noviny in 1996, 1998, 2000, 2004 and 2009. The work confronts in the long-term overview the media agenda (the actual number of articles and topics that HIV / AIDS in those years dedicated to) with the real number of newly reported HIV positive and monitors the expanses of Ministry of Health on prevention in this area. The work responds to the question whather are the topics of HIV / AIDS media normally handled episodically, with emphasis on the story, identifies the main issues in the context of HIV / AIDS in the media, namely celebrities in particular frequent topic in the context of HIV / AIDS is deeply engaged. The work also confronts the results of media coverage of this topic so far incurable disease AIDS in czech newspapers with foreign studies on the ground of Media Studies. The actual analysis has two specific aspects of pursuing the use of different analytical tools. Quantitative content analysis looks at the articles that the newspapers reporting on the topic of HIV / AIDS appear. The second part adds a qualitative study on the topic of celebrities and HIV / AIDS. The aim of case studies is to show the...
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Preparation and Characterization of Protein Binders Mimicking Epitopes of HIV-1 Neutralizing Antibodies
Šulc, Josef ; Malý, Petr (advisor) ; Novotný, Marian (referee)
For three decades, the ongoing HIV pandemic has taken the lives of tens of millions of people. Still, more tens of millions are fighting this incurable disease today. Current failures in combating this global problem are caused mainly by the virus's extreme ability of mutation, its very effective molecular shield which repels the immune system's attacks, and its immense variability. A breakthrough, achieved relatively recently, is the discovery of the so-called broadly neutralizing antibodies against HIV-1, which carry a very efficient and broad neutralizing response. So far, it's not known how to elucidate the production of these antibodies in the infected hosts to quell or altogether eliminate the virus. This work deals with experimental results, which led to both in vivo and in vitro proof-of-concept of the so-called protein mimetics, the ability to imitate viral surface epitopes, and therefore stimulate an efficient immune response carried by targeted broadly neutralizing antibodies. This effect is mediated by recombinant binding proteins, based on the Myomedin scaffold. This work describes the selection and characterization of these binding proteins mimicking the epitopes of one of the most effective broadly neutralizing antibodies, 10E8. It shows that the binding affinities of selected...
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Structural studies of LEDGF/p75 interactions
Těšina, Petr
3 ABSTRACT LEDGF/p75 protein is a human transcriptional co-activator and epigenetic reader associated with transcriptionally active chromatin. It is crucial for HIV integration and MLL1 fusion-driven leukemia development. Interactions of LEDGF/p75 with HIV integrase (HIV IN) and MLL1-menin complex are considered an attractive therapeutic target for drug development. LEDGF/p75 interacts with both HIV IN and MLL1-menin complex through its integrase binding domain (IBD). While the pathophysiological interactions of LEDGF/p75 IBD were intensively studied, little was known about the physiological ones. In addition to HIV IN and MLL1, the LEDGF/p75 IBD also interacts with JPO2, PogZ, ASK and MLL2. In search for specific inhibitors of LEDGF/p75 IBD interaction with HIV IN and MLL1, it is essential to obtain detailed information about its interactions with all binding partners. The IBD-MLL1-menin complex has been structurally characterized, but only partially. Using NMR spectroscopy, we identified and mapped a novel part of the IBD-MLL1 interface. This additional interface is able to maintain the interaction between LEDGF/p75 and MLL1 even without the presence of menin, which was considered necessary. Moreover, colony forming assays of primary leukemic blasts revealed that this additional interface is essential for...
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Optimizing of the regime of marker's examination of clinically important infections in blood donors
Dušková, Daniela ; Tesař, Vladimír (advisor) ; Borovanský, Jan (referee) ; Průša, Richard (referee)
Project title: Optimalization of the regime of marker's examination of clinically important infections in blood donors Project author: Daniela Dušková, M.D. Project supervisor: prof. Vladimír Tesař, M.D., Dr.Sc., MBA, FASN The aim of this project is to contribute to the discussion about introducing the methods of molecular biology into the routine blood donor testing in the transfusions departments in the Czech Republic. The theoretical part includes a brief history and some turning points in transfusion medicine. The next part within the theoretical section is dedicated to the problems of infectious diseases concerning transfusion and the general examination processes used during the selection of blood donors. The end of the theoretical part concentrates on existing possibilities of markers' examination of clinically important infections in blood donors, including the list of processes performed in the Czech Republic, the European Union and other countries. The practical part describes this study, ie. the routine screening test of blood donors using the CMIA method (a routine method) and using RT-Real Time PCR method (a molecular biology method) for detecting infectious markers (HCV, HBV, HIV). Within this part, the principle of both methods and the process of actual examinations are described in...
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The possibility of determination of HIV antibodies avidity for early infection detection
Diničová, Michaela ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Specialist on Laboratory Methods Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: The possibility of determination of HIV antibodies avidity for early infection detection The determination of early HIV infection in the Czech Republic is based on a combination of results of laboratory examination, clinical examination, and information from an epidemiological report. The identification of patient in the acute phase of the disease allows to search for targeted contact to reduce further spread of HIV, as patients in the early phase of the disease are the riskiest for transmission of infection. One of the laboratory markers of the acute phase of infection is low avidity of antibodies, which expresses the strength of bonds between antigen and antibody. The determination of avidity is based on fact that avidity in recent infections is low because antibodies do not bind tightly enough to antigen and avidity increases when the immune response matures. Quantitatively, it is expressed by the avidity index, which determines what part of the antibodies (%) will remain bound in complex with the antigen after incubation with chaotropic agent, in our case with guanidine...
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Terapeutické využití dendritických buněk
Svobodová, Hana
Dendritic cells (DC) are the most effective antigen presenting cells. They are able to detect the presence of the antigen and ensure the transmission of information to the lymph nodes where T lymphocytes are stimulated by these mechanisms. DC mature after encountering the antigen, wander to the lymph nodes and other secondary lymphatic organs, and change from antigen-binding cells to active antigen presenting cells. They are also critical for regulating of immune response that affect the differentiation of T cells towards the Th1 or Th2 response. Cultivation of dendritic cells in vitro enables manipulation with these cells and discovering new therapies for controlling human diseases. Their specific properties have a great potential to be used not only for antitumor therapy but also in the treatment of infectious, autoimmune and allergic diseases. In particular, the induction of CD8+ T cells by activating the immune system can contribute to inhibition of tumor growth and increase patient survival. Encouraging results were also reported using immature dendritic cells in transplantology.
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MHC And KIR Genotyping Of Macaques In HIV Infection Research
Matula, Jan
Modern research of viral diseases relies on genomic data processing. Not only is the sequence of a virus important, genomic sequence of specific receptors in affected organisms also plays an important role. In this paper, a novel package for processing of next generation sequencing data in infectious disease written using R/Bioconductor language is proposed. Functionality of the package, including implementation of advanced SSAHA algorithm for fast database searches, in demonstrated using genotyping of genes for MHC and KIR receptors of HIV positive macaques.
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