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Directed evolution of an HIV-1 LTR specific recombinase for anti-retroviral therapy- a proof of concept studySarkar, Indrani 17 January 2007 (has links) (PDF)
The prospect of the work presented in this thesis has been to engineer Cre recombinase to recognize and recombine a sequence from an HIV-1 Long Terminal Repeat (LTR), characterize the recombination proficiency of the evolved recombinase in mammalian cells and explore the potential of the recombinase for a novel antiretroviral strategy.
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Directed evolution of an HIV-1 LTR specific recombinase for anti-retroviral therapy- a proof of concept studySarkar, Indrani 26 September 2006 (has links)
The prospect of the work presented in this thesis has been to engineer Cre recombinase to recognize and recombine a sequence from an HIV-1 Long Terminal Repeat (LTR), characterize the recombination proficiency of the evolved recombinase in mammalian cells and explore the potential of the recombinase for a novel antiretroviral strategy.
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Veränderungen in der Genexpression fremdstoffmetabolisierender Enzyme und Bedeutung genetischer Polymorphismen unter besonderer Berücksichtigung von HIV-VirustatikaGashaw, Isabella 20 October 2003 (has links)
Die Therapie der HIV Infektion besteht aus Kombination mehrerer antiretroviraler Substanzen und birgt ein erhöhtes Risiko an Arzneimittelwechselwirkungen. Das bekannte Problem der Virusresistenz kann zudem durch Enzyminduktion begünstigt werden. Das Ziel der vorliegenden Arbeit lag in Untersuchungen zu Einflüssen der Virustatika auf die Expression von Cytochrom P450 Enzymen: 1A1, 1B1, 3A4 sowie der P-Glykoproteins (MDR1) an immortalisierten Zellsystemen. Die Protease Inhibitoren Indinavir, Nelfinavir, Ritonavir und Saquinavir induzierten die Regulation der mRNA Expression über den Aryl-Kohlenwasserstoff-Rezeptor (AhR) und den Pregnan-X-Rezeptor (PXR) dosisabhängig und signifikant. Die Nukleosidischen Reverse Transkriptase Inhibitoren Zalcitabin, Zidovudin und Lamivudin sowie der Nicht-Nukleosidische Inhibitor Nevirapin zeigten induktive Eigenschaften nur für die AhR Zielgene CYP1A1 und CYP1B1. Amprenavir und Efavirenz aktivierten die PXR-Regulation. Die möglichen Auswirkungen der Induktion der untersuchten Gene wurden ausführlich diskutiert. Die molekularen Grundlagen der interindividuell variierenden Aktivität von CYP3A wurden in einer Probandenstudie untersucht. Es wurden die mRNA Expression in den Leukozyten, die Aktivität des Enzyms und einige bekannte Polymorphismen unter Einwirkung von Rifampicin untersucht und diskutiert. / The therapy of HIV infection requires a combination of several antiretroviral substances accompanying risk factors for drug-drug interactions. Moreover, virus resistance can be promoted by enzyme induction caused by antiretroviral drugs. The aim of the study was to investigate the influences of antiretroviral substances on the expression of cytochrome P450 enzymes: 1A1, 1B1, 3A4 and p-glycoprotein (MDR1) using immortalized cell systems. The protease inhibitors indinavir, nelfinavir, ritonavir and saquinavir induced significantly the regulation of mRNA expression through the aryl hydrocarbon receptor (AhR) and the pregnane-x-receptor (PXR) in a concentration-dependent manner. The nucleoside reverse transcriptase inhibitors zalcitabine, zidovudine and lamivudine and the non-nucleoside reverse transcriptase inhibitor nevirapine showed inductive properties only for the AhR target genes CYP1A1 and CYP1B1.Amprenavir and efavirenz activated the PXR target genes. Potentially effects of the described induction are discussed. In a second part of the work, the molecular mechanisms of the individual varying activity of the CYP3A enzyme were investigated applying an in vivo study. CYP3A4 mRNA expression and rifampicin mediated induction in leucocytes were correlated with systemic enzyme activity under induction and known polymorphisms.
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The Social Impact of HIV-Seropositivity and Antiretroviral Treatment on Women in Tanga, Tanzania. A Qualitative Study.Bohle, Leah F. 13 November 2017 (has links)
No description available.
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