Weight loss and depletion of fat-free mass commonly occurs in patients with COPD. The objective of the study was to determine the magnitude and duration of protein depletion during an episode of acute exacerbation. Fifteen patients (9 women and 6 men) admitted for an acute exacerbation of COPD participated in a descriptive study that prospectively measured individual nitrogen balance over a 6-week follow-up period using repeated nitrogen balance tests. / The mean nitrogen balance in hospital was -13.20 +/- 11.63 g N/day. Only 2 patients achieved a positive nitrogen balance by 2 weeks post-admission and 4 more patients by 4 weeks post-admission. At 6-weeks post-admission, 7 patients (47%) were still in negative nitrogen balance (-10.75 +/- 9.34 g N/day). Protein and energy intakes were significantly higher in patients who achieved a positive nitrogen balance (1.7 +/- 0.5 g protein/kg/day and 120 +/- 30% of estimated energy expenditure (1.7 x REE)) than patients who remained in a negative nitrogen balance (1.3 +/- 0.6 g protein/kg/day and 70 +/- 20% of estimated energy expenditure). There were no significant changes in weight or handgrip strength over the follow-up period. No effect of cumulative or daily corticosteroid doses on nitrogen balance or changes in handgrip strength were found. / In conclusion, the catabolic stress of an acute exacerbation on nutritional status is remarkable. Patients admitted for an acute exacerbation of COPD are in severe negative nitrogen balance, which improves very slowly post-discharge. A negative nitrogen balance is prolonged in patients who have a decreased protein and energy intake.

Thesis (M.Sc.)--University of Adelaide, 1952. / "November 1951." Includes bibliographical references.

Thesis (M.S.)--Michigan State University. Dept. of Physiology, 2008. / "Committee members, Weiming Li, Richard Miksicek, and Cheryl Sisk"--Acknowledgments. Title from PDF t.p. (viewed on Aug. 4, 2009) Includes bibliographical references (p. 51-54). Also issued in print.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2007" Includes bibliographical references.

Dissertation (PhD)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.

Thesis (M.Sc. (Pharmacy)) - Rhodes University, 2007.

Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17-valer ate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base c aused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained f r om the systematic stUdies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society. / KMBT_363 / Adobe Acrobat 9.53 Paper Capture Plug-in

ix, 120 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Gene duplication underlies the evolution of many protein functions and is a known stimulus for molecular innovation. Many models exist to explain the maintenance of duplicate genes in the genome and the dynamics that drive the evolution of novel protein functions; few if any of these models, however, incorporate knowledge of how protein structures and functions actually evolve. A growing body of work on the historical mechanisms of molecular evolution and the ways in which proteins evolve in the lab has provided profound insights into the ways in which proteins respond to mutation, selection, and drift. Evolutionary models of duplicate gene evolution could greatly benefit from the knowledge gained from these mechanistic studies of protein evolution. My dissertation seeks to address this gap in knowledge by reconstructing the process by which novel steroid signaling pathways evolved after gene duplication. I focus specifically on a class of hormones called corticosteroids--critical regulators of the stress response, metabolism, and immunity--and the mineralocorticoid and glucocorticoid receptors that mediate the steroid response. Both the enzymes that synthesize corticosteroids and the hormone receptors are the result of ancient gene duplication events, and I make use of methods in phylogenetics, molecular biology, and structural biology to reconstruct the mechanisms and dynamics by which they evolved. This dissertation comprises three separate but complementary studies that illuminate the origins of corticosteroid signaling. In the first project, I show how lineage-specific steroid signaling arose in elasmobranchs as a novel hormone exploited the structural promiscuity of preexistent receptors. Next, I describe how degenerative and stabilizing mutations defined the divergence of the glucocorticoid receptor after gene duplication. And finally, I use phylogenetic and functional analyses to reconstruct the origins of corticosteroid synthesis with the duplication of enzymes in the steroid synthesis pathway. Together, I provide a comprehensive reconstruction of the evolution of corticosteroid signaling. This work also highlights specific evolutionary mechanisms--molecular exploitation, structural and functional promiscuity, degenerative mutations, and stabilizing mutations--that could drive the evolution of novel protein functions after gene duplication. This dissertation includes both previously published and unpublished co-authored materials. / Committee in charge: Patrick Phillips, Chairperson, Biology; Joseph Thornton, Advisor, Biology; William Cresko, Member, Biology; John Postlethwait, Member, Biology; Kenneth Prehoda, Outside Member, Chemistry

Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.

The study of conformation in drug action can be approached from two directions, (i) that of the drug, and (ii) that of the receptor. Since the problem of elucidating the biologically active conformation of drug molecules has been extensively studied and is very well reviewed1,2, it should be equally productive to explore the conformational aspects of receptors. Before a plausible model of conformational requirements at the receptor level can be developed, it is necessary to know something about the nature of the biologic receptors. Although structural details for specific receptors are generally unknown and a fascinating challenge for the medicinal chemist to study, the following considerations suggest that most receptors are lipoproteins with the ability to interact with specific substrates at their active sites. The known characteristics of receptors can be summarized as follows: a. Receptors can bind with a wide variety of drug molecules, suggesting a degree of conformational adaptability, a characteristic of proteins. b. Some receptors exhibit a relatively high degree of stereospecificity, a property shared by enzymes. c. Most receptor-like substances which have been isolated have been found to be proteolipid complexes, some of which may include phospholipids and prostaglandins if they are membrane-bound. Its seems pertinent to mention that the problems involved in the isolation and characterization of drug receptors are formidable. The procedures employed in the extraction and purification of receptor-like substances are laborious and time-consuming, and the isolated material is, at best, only partially pure. Moreover, the results of drug-binding studies on such partially purified receptors are often equivocal. The hypothesis of induced conformational changes has been reviewed by several authors.5,6 For example, Koshland7,8,9 suggested that the active site of an enzyme does not need to be absolutely complementary to that of the substrate, but after interacting with it, induction of conformational changes can occur which might result in complementarity. Thus, it may be logical to assume on the basis of this hypothesis that in combining with an enzyme the substrate induces a change in its conformation. This results in an enzymatically active orientation of the catalytic groups. The biological response resulting from such a combination depends mainly upon the induction of an appropriate conformational change.