<p>PXR mediated elevation of CYP3A4 expression is a costly problem in drug development as well as a clinical problem due to clinically important drug interactions caused by the enzyme induction. CYP3A4 is responsible for the metabolism of more than 50% of the drugs commonly used today. Many of these, as well as other compounds e.g. in herbal medicines can induce transcription of CYP3A4 and thereby enhance the metabolism of other drugs, rendering them ineffective or more toxic. By using an in vitro assay for CYP3A4 induction, tests can be performed on candidate drugs early in development and thereby save time and resources since CYP3A4 inducers are eliminated from further development. A reporter gene assay was constructed by inserting three modules, which includes PXR binding sites isolated from the CYP3A4 sequence, in front of a luciferase gene. This construct was transfected together with PXR into HEK 293 cells. Induction was evoked by adding rifampicin, a known CYP3A4 inducer, to the medium. After lysis of the HEK cells and addition of luciferase substrate, luminescence intensity was recorded as a measure of induction. The construct worked and consistently showed induction by rifampicin, but could be further improved to yield higher sensitivity.</p>

Thesis (Ph.D.)--University of Wyoming, 2008. / Title from PDF title page (viewed on August 5, 2009). Includes bibliographical references (p. 123-138).

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 220-243). Available also in a digital version from Dissertation Abstracts.

Thesis (M.S.)--Florida State University, 2003. / Advisor: Dr. Shridhar K. Sather, Florida State University, College of Human Sciences, Dept. of Nutriton, Food and Excercise Sciences. Title and description from dissertation home page (viewed 5/4/04). Includes bibliographical references.

Thesis (doctoral)--Universität, Giessen, 1999.

Thesis (doctoral)--Universität, Hohenheim, 2000.

Over the last few years the World Health Organization (WHO) has endorsed several tests for the rapid detection of multidrug-resistant tuberculosis (MDR-TB) in resource-poor settings. The objective of this study was to compare the cost-effectiveness of a line probe assay test (less than one week for results) to conventional (bacterial culture) drug susceptibility testing (one month for results) for the detection of MDR-TB in an HIV-positive South African population by estimating the incremental cost-effectiveness ratio (ICER) per disability-adjusted life-year (DALY) averted. Costs of testing, drug treatment, hospitalization, as well as estimates for mortality, treatment success, and failure rates were obtained from literature sources, the South African Department of Health, the WHO, the Foundation of Innovative Diagnostics (FIND), and expert opinion. The willingness-to-pay threshold for a DALY averted was pre-set at 3 times the 2009 GDP per capita (about $17,400) for South Africa. In the base-case scenario for a prevalence of 30% of MDR-TB among HIV-positive patients, the average cost per person for the line probe assay testing strategy was $3,539/0.458 DALY averted and the conventional testing approach was $3,011/0.430 DALY averted. The base-line ICER was about $18,800 per DALY averted – about $1,400 above the pre-set threshold. In sensitivity analyses, the model was robust to changes in prevalence (+ 50%); costs (+ 10%), and probabilities of death, success and failure (+ 20%). However, when the treatment success rate for the line probe assay test was increased to 60% (one of the targets set by WHO in TB treatment) the ICER was below the willingness-to-pay level (i.e., cost-effective). The probabilistic sensitivity analysis showed there is a 70% chance that the additional cost of the line probe assay, compared with conventional testing, was less than $30,000 per DALY averted. However, the model may have underestimated the benefits of the line probe assay because it did not account for a decrease in the transmission of the disease due to earlier treatment nor did it measure any benefits more than a year after testing. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

 The emergence of the pandemic H1N1 2009 virus of swine-origin and its transmission back to swine highlighted the need for global surveillance of swine influenza. Serology can help to address the epidemiological situation of influenza infection. Since typical serology tests such as hemagglutination inhibition or microneutralization assays are subtype and partially virus-lineage specific, it is important to select appropriate viral antigens for such studies. A poorly chosen panel of antigens will lead to underestimation of the seroprevalence. The choice of well-matched antigen is difficult if there is no prior virological surveillance in that area and even if there was virological surveillance data, transient infections may go undetected. Hence an universal influenza A type reactive serological test is needed. While such tests are available for poultry, there is little published data on the performance of these commercial influenza ELISA assays for serology on swine sera. In this study we evaluated 3 commercially available competitive ELISA assays, IDEXX? Influenza A Ab test, IDEXX? AI MultiS-Screen Ab Test and IDVet ID Screen? Influenza A Antibody Competition ELISA kit for detecting influenza type A reactive antibodies in swine. The virus antigens and the serum samples were obtained from a 14-year systematic abattoir-based virological and serological surveillance for swine influenza in southern China. The performance was evaluated by ROC curve and scatter plot, together with other statistical parameters including the Youden index to optimize the cut-off levels. Using the optimized cut-off levels, sensitivity and specificity of the IDEXX? Influenza A Ab test was 86% and 89% respectively; for IDEXX? AI MultiS-Screen Ab Test was 91% and 87% and for IDVet ID Screen? Influenza A was 95% and 79%, respectively. These findings help to provide different cut-off levels to maximize the sensitivity or specificity to suit different purposes. We found that the ELISA assay was useful in detecting serum samples that may be positive for influenza antibody but missed in the serology screening tests due to limitations in the chosen antigen panel. The ELISA assay maybe helpful in global swine influenza surveillance programs. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences