Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains viii, 51 p. : ill. Includes abstract. Includes bibliographical references (p. 39-42).

This thesis aimed to investigate the features and properties of the ground states, transient species and photoproducts involved in the photophysical and photochemical processes for four kinds of drug compounds: lomefloxacin (LF), norfloxacin (NF), tiaprofenic acid (TPA), and flurbiprofen (Fp). The investigation used femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), UV/Vis absorption spectra (UV/Vis), nanosecond transient resonance Raman (ns-TR2) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3), as well as density functional theory (DFT) calculations. Although many previous investigations have indicated that photo-defluorination or photo-decarboxylation reactions may account for the phototoxicity for these compounds, detailed information on the mechanisms remains unclear. In this thesis, the photo-defluorination reaction of LF was explored in neutral water at pH 7.2. The fs-TA results revealed that the lowest lying excited singlet state species (S1) partially decayed into the ground state through fluorescence emission and partially underwent cleavage of the carbon-fluorine bond at position 8 to generate into a singlet aryl cation. Subsequently, intersystem crossing (ISC) allowing the transformation from singlet cation to triplet carbene was observed. Finally, a cyclization reaction with the N-ethyl chain took place for the triplet carbene to generate the final product. The mechanism underlying NF phototoxicity involves a photo-defluorination reaction in neutral water (pH=7.2). The fs-TA spectra indicated that the S1 underwent efficient ISC to swiftly transform into lowest excited triplet (T1) The ns-TA gained under nitrogen-saturated condition observed a new transient species produced from T1 that was proposed to be a transient species derived from the photo-defluorination reaction involving a SN2Ar* mechanism. The photo-defluorinated product ultimately experienced an ISC process to produce the final product. The photo-decarboxylation mechanism of TPA was studied in a neutral phosphate buffered solution (PBS). The fs-TA data revealed that S1 went through an efficient ISC to rapidly transform into T1 that then undergoes a photo-decarboxylation reaction to produce a triplet biradical species (denoted as TB3). The ns-TA and ns-TR3 results supplied evidence of the protonation process of TB3 that produces the neutral species (denoted as TBP3) that then decayed through ISC to give rise to the singlet TBP species, which underwent further reaction to make the final product (DTPA). The photo-decarboxylation reaction of Fp was explored in pure acetonitrile (MeCN). The second excited singlet (S2) went through internal conversion (IC) to decay to S1. Intriguingly, three different pathways for S1 decay co-exist. One pathway is fluorescence emission and the second is an ISC process. The third pathway is the homolysis of the carbon α bond reaction that proceeds to generate two radical species, one being a carboxyl species and the other being the residual, denoted as FpR that was liable to be oxidized under an oxygen-saturated condition to yield a new radical species with the addition of one oxygen molecule which is denoted as FOR that then experienced intramolecular hydrogen transfer (IHT) and dehydroxylation (DHO) to produce the final product. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

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High output of prostaglandins (PGs) are the hallmark of inflammatory and immune reactions. A rate-limiting step in the production of PGs is the presence of the enzyme cyclooxygenase (COX). COX exists as two isoforms: COX-1 which is constitutively expressed in most cells and COX-2 which is inducible by LPS, proinflammatory cytokines and other stimuli in cells involved in inflammation. The objective of this study was to determine the effect of nonsteroidal antiinflammatory drugs and proinflammatory cytokines on COX-2 expression in human macrophages. COX-2 specific (NS-398) and non-specific (aspirin, indomethacin and naproxen) inhibitors showed no effect on COX mRNA and protein expression induced by LPS. In contrast, the drugs markedly inhibited COX activity as measured by the accumulation of PGE2. The induction of COX-2 mRNA expression by LPS was rapid and sustained. However, LPS only transiently stimulated the transcription of COX-2 gene and activation of the transcription factor NF-kappaB. LPS stimulated the release of IL-1beta and TNF-alpha but these cytokines had no autocrine effect on the transcriptional or post-transcriptional regulation of COX-2. The presence of LPS was essential for the maintenance of high levels of long-lived COX-2 mRNA. As IFN-gamma is a major macrophage activating factor, we determined the role of this cytokine on COX-2 expression induced by exogenous IL-1beta. IFN-gamma-primed macrophages showed significantly lower levels of COX-2 mRNA, protein and PGE2 production compared to non-primed cells. IFN-gamma specifically decreased the transcriptional activation of COX-2 gene by IL-1beta but not by LPS without affecting the rate of mRNA decay. These results demonstrate that sustained production of PGE2 by macrophages in an inflammatory milieu can occur through the stabilization of COX-2 mRNA and revealed a role for IFN-gamma as an anti-inflammatory cytokine counteracting the expression of COX-2. A better understanding of COX-2 regulation will

Copies of author's previously published articles in back-cover pocket. / Bibliography: leaves 180-205. / x, 205 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines aspects of the potential enantioselective pharmacokinetics and pharmacodynamics of ketoprofen in humans, and develops methods for quantifying total (bound plus unbound) and unbound ketoprofen enantiomers in plasma. / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 1993?

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 76-77) Also available in print.

Thesis (Ph.D.)--Kent State University, 2006. / Title from PDF t.p. (viewed Mar. 11, 2009). Advisor: John J. Docherty. Keywords: herpes simplex, virus, resveratrol, NF-kappaB, NSAID Includes bibliographical references (p. 100-105).

Thesis (M.S.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains vii, 62 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 41-44).

Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains viii, 59 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 33-38).

Thesis (M.S.)--University of Louisville, 1997. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.