dc.contributor.advisor | Booth, Frank W. | eng |
dc.contributor.author | Steffen, Brian | eng |
dc.date.issued | 2007 | eng |
dc.date.submitted | 2007 Fall | eng |
dc.description | Thesis (Ph. D.) University of Missouri-Columbia 2007. | eng |
dc.description | "December 2007" | eng |
dc.description | 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. | 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.bibref | Includes bibliographical references. | eng |
dc.identifier.merlin | b63346345 | eng |
dc.identifier.oclc | 226714397 | eng |
dc.identifier.uri | https://hdl.handle.net/10355/6001 | |
dc.identifier.uri | https://doi.org/10.32469/10355/6001 | eng |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | Access is limited to the campuses of the University of Missouri. | eng |
dc.subject.mesh | Tumor Necrosis Factors -- antagonists & inhibitors | eng |
dc.subject.mesh | Pentoxifylline -- therapeutic use | eng |
dc.subject.mesh | Receptors, Tumor Necrosis Factor, Type I -- therapeutic use | eng |
dc.subject.mesh | Heart Failure -- complications | eng |
dc.subject.mesh | Cachexia -- therapy | eng |
dc.title | Efficacy of TNF inhibitor treatment in a model of heart failure and resulting cachexia | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Medical Pharmacology and Physiology (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph. D. | eng |