Translational developments in the study of sepsis: investigations into molecular pathways, experimental modelling and applications of novel biomarkers

McCarron, Eamon Translational developments in the study of sepsis: investigations into molecular pathways, experimental modelling and applications of novel biomarkers. Master of Philosophy thesis, University of Liverpool.

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Abstract

Sepsis is a significant problem in the United Kingdom with diagnosis, management and prognosis proving difficult for clinicians. This is further exacerbated by the lack of sensitive and specific biomarkers for the disease and complications related with it (i.e. organ dysfunction). The lack of biomarkers and efficacious therapeutic intervention is a result of inadequate understanding of this disconnect between murine and human sepsis on a molecular level and in vivo. In this analysis, comparison of molecular signalling pathways involved in inflammation has revealed a possible source for this disconnect. Comparative analysis of two well characterised murine models of sepsis (LPS and faecal peritoneal inoculation) has further demonstrated that the difficulty in recapitulating a similar environment of human sepsis in rodents widens the gap that the translational bridge must cross. Both models showed a similar level of change consistent with an acute systemic inflammatory response, but discrete differences show the superiority of the faecal inoculation as a reproducible, valid and more reliable model of murine sepsis. HMGB1 and cleaved/uncleaved CK18 have been shown to be accurate ways of monitoring the level of inflammation, necrosis and apoptosis in the literature. Their application to defined groups of ICU patients, who could potentially benefit from them, has shown that there is potential for a clinical application. Their use alongside currently used markers of liver function could enhance the overall picture that clinicians have when approaching these patients. However, further research is needed involving larger sample sizes and more scrupulous statically analysis before widespread application can occur.

Item Type:	Thesis (Master of Philosophy)
Additional Information:	Date: 2012-08 (completed)
Divisions:	Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	05 Sep 2013 09:49
Last Modified:	16 Dec 2022 04:38
DOI:	10.17638/00009953
URI:	https://livrepository.liverpool.ac.uk/id/eprint/9953