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dc.contributor.advisorBooth, Frank W.eng
dc.contributor.authorSteffen, Brianeng
dc.date.issued2007eng
dc.date.submitted2007 Falleng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2007.eng
dc.description"December 2007"eng
dc.descriptionThe 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.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The aim this dissertation was to explore the efficacy of tumor necrosis factor (TNF) inhibitors in attenuating increases in both anorexia and the ubiquitin proteasome pathway transcripts in cardiac cachexia, a potentially lethal condition that responds poorly to current treatments. Right heart failure and subsequent cardiac cachexia was rapidly induced with monocrotaline injection in Sprague-Dawley rats and either soluble TNF receptor-1 or the general inhibitor of TNF production, pentoxifylline, was given to diminish TNF action upon the first indication of cachexia. Ubiquitin proteasome pathway transcripts and western blotting were analyzed in skeletal muscle. Both soluble TNF receptor-1 and pentoxifylline attenuated losses in both body weight and skeletal muscle mass and also reduced the transcriptional activation of the ubiquitin proteasome pathway. The action of soluble TNF receptor-1 was partly through reversal of reduced food consumption, while the effects pentoxifylline were independent of food intake. The following dissertation shows that not only does soluble TNF receptor-1 treatment attenuate anorexia in monocrotaline-induced cardiac cachexia, but that this anti-anorectic effect is responsible for attenuating the induction of some ubiquitin proteasome pathway transcripts as well as preserving body weight and skeletal muscle mass. Though further investigation is needed, sTNFR1 may have clinical efficacy in combating cachectic states brought on by heart failure.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.identifier.merlinb63346345eng
dc.identifier.oclc226714397eng
dc.identifier.urihttps://hdl.handle.net/10355/6001
dc.identifier.urihttps://doi.org/10.32469/10355/6001eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.subject.meshTumor Necrosis Factors -- antagonists & inhibitorseng
dc.subject.meshPentoxifylline -- therapeutic useeng
dc.subject.meshReceptors, Tumor Necrosis Factor, Type I -- therapeutic useeng
dc.subject.meshHeart Failure -- complicationseng
dc.subject.meshCachexia -- therapyeng
dc.titleEfficacy of TNF inhibitor treatment in a model of heart failure and resulting cachexiaeng
dc.typeThesiseng
thesis.degree.disciplinePhysiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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