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Ghrelin, motilin in health and disease
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Sung, E. Z. H. (2012) Ghrelin, motilin in health and disease. MD thesis, University of Warwick.
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WRAP_THESIS_Sung_2012.pdf - Submitted Version Download (3101Kb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b2585105~S1
Abstract
Ghrelin is a 28 amino-acid peptide produced predominantly by the stomach. Two main
isoforms of ghrelin are currently known (octanoyl- and desoctanoyl ghrelin). It
functions as a circulating orexigenic hormone In addition, it has an effect on the
nervous, cardiovascular and immune system. Current data suggest that ghrelin may have
beneficial anti-inflammatory effects. Chapter 3 in this thesis primarily examines the
relationship between ghrelin and inflammation in Crohn’s disease (CD). Modulation of
inflammation with infliximab, a powerful anti-TNFα antibody therapy, can increase
total ghrelin concentration by 25%. In addition, a normal physiological post-prandial
decrease in ghrelin following a meal is restored when infused with infliximab,
suggesting a dysregulation of ghrelin in CD patients with active inflammation. At
cellular level, there is evidence that ghrelin may have an immunosuppressive effect on
activated T-lymphocytes. Chapter 4 of this thesis examines the effect of ghrelin, a
manufactured agonist and des-octanoyl ghrelin on NFκB activation on a human Blymphocyte
cell line. This study demonstrated that exposure to octanoyl ghrelin confers
an initial increase of NFκB activation in inactivated cells of up to 50% which suggests a
pro-inflammatory effect. However, NFκB activation appears to decrease at much higher
concentrations of octanoyl ghrelin, which may indicate toxicity at supra-physiological
levels. Ghrelin is also involved in the regulation of gastric motility and has structural
similarities to motilin. Symptoms of delayed gastric emptying can occur long after
cancer chemotherapy has ended. Chapter 5 of this thesis compares the contractility and
pro-motility neurotransmitter expression in chemotherapy and non-chemotherapy
exposed stomach tissues obtained from patients undergoing surgery for oesophagogastric
cancers. Chemotherapy exposed tissues have reduced contractility to carbachol
and apparent destruction of the cholinergic activity. The tendency for ghrelin receptors
to increase suggests an attempt to upregulate compensating systems. In conclusion,
ghrelin can be altered by inflammation and may have beneficial effects on gastric
motility.
Item Type: | Thesis (MD) | ||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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Library of Congress Subject Headings (LCSH): | Ghrelin, Crohn's disease -- Etiology, Inflammation -- Physiology, Inflammation -- Treatment, Cancer -- Chemotherapy -- Complications | ||||
Official Date: | July 2012 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | MD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Nwokolo, Chuka U. ; O'Hare, Paul | ||||
Extent: | xiv, 163 leaves, 25 unnumbered leaves : illustrations, charts | ||||
Language: | eng |
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