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TitleBioinformatics analysis of control mechanisms of burn and sepsis induced inflammatory response
NameOrman, Mehmet Ali (author), Ierapetritou, Marianthi G (chair), Berthiaume, Francois (co-chair), Androulakis, Ioannis P (internal member), Sunderram, Jagadeeshan (outside member), Rutgers University, Graduate School - New Brunswick,
Degree Date2011-10
Date Created2011
SubjectChemical and Biochemical Engineering,
Bioinformatics,
Burns and scalds—Complications,
Inflammation—Immunological aspects
DescriptionBurn injury and infections can lead to an uncontrolled and prolonged action of inflammatory response in the body, which increases the mortality rate of patients. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to develop animal models exhibiting patho-physiological behaviors similar to those of patients. This was addressed, in this study, by a systematic analysis of local and systemic responses -including the measurements of inflammatory mediators, gene expression and metabolic profiles of liver- in rat models receiving 20% total body surface area (TBSA) scald burn injury or cecal ligation and puncture (CLP) treatment. All animal groups had 100% survival for at least 10 days following treatments. CLP caused a ~10% weight loss indicating an accelerated breakdown of skeletal muscle protein. It was found that a certain number of cytokines and chemokines, such as MCP-1, GROK/KC, IL-12, IL-18, and IL-10, were significantly altered following the treatments including SCLP (control of CLP) which is a sterile surgical treatment where cecum is not ligated and punctured. Gene expression analysis elucidated that hepatic transcriptional response to burn injury was mainly related to pro-inflammatory and anti-inflammatory gene groups and genes involved in lipid biosynthesis and central carbon metabolism. Shortly after the CLP treatment, genes related to Toll like receptors and MAPK signaling pathway were significantly up-regulated. Significant changes in the genes associated with acute phase protein synthesis were also observed following the burn and CLP. Furthermore, perfusion experiments elucidated that hepatic metabolic response to burn injury and sepsis was characterized by an up-regulation of pathways including gluconeogenic reactions (sources of which are mainly lactate, aspartate, glycerol and glutamine), urea production from arginine, and serine-glycine inter-conversion. On the other hand, weight values of these pathways were dramatically decreased following the SCLP treatment. In summary, in this study, bioinformatics tools (clustering and metabolic network analysis algorithms) and animal models of burn and CLP were utilized to understand the various layers of regulation and capture the entire scope and complexity of the inflammatory response.
NotePh. D.
NoteIncludes bibliographical references
Noteby Mehmet Ali Orman
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000063564
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.