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Title: Nuclear magnetic resonance spectroscopy as a tool to assess pathophysiological changes in liver disease
Author: Dabos, Konstantinos John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The aim of this thesis was twofold. First we wanted to validate the use of 1H NMR spectroscopy as a reliable technique to observe and quantitate low molecular weight substances in the context of liver disease. We then wanted to provide some insight into the performance of key metabolic pathways in hepatocytes that are either cultured or failing in the native liver of patients. We validated out technique by comparing concentrations of low molecular weight substances measured by NMR with results from standard biochemical assays and HPLC. We used primary porcine hepatocytes and studied the effect of different culture conditions and modalities on the metabolism of those cells by looking at the supernatant of the cell cultures. We have shown in this thesis that culture conditions and culture media are factors that greatly influence the performance of key metabolic pathways of cultured hepatocytes and this in turn, influences the life span of cell in culture. We then investigated the changes in key metabolites in the plasma from patients suffering from chronic liver failure and its complication chronic hepatic encephalopathy and from patients with acute liver failure and compared those concentrations with controls. Key metabolic pathways were impaired in patients with chronic liver failure compared to controls. Further impairment of branch chain amino acids and ketone bodies metabolism was noted in chronic hepatic encephalopathy. In acute liver failure gluconeogenesis was greatly impaired along with ketogensis at the early stages of the disease. In conclusion NMR spectroscopy is capable of providing accurate estimations of concentrations of low molecular weight substances in biofluids and thus can give us an insight in the pathogenesis of cell dysfunction in liver disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available