The major part of this thesis is to obtain basic information in regard to changes of amino acids and middle molecular substances in fulminant hepatic failure (FHF) using a galactosamine induced rat model. The changes of these substances after hemoperfusion were also studied. / A generalized elevation of amino acid concentrations is demonstrated in the systemic blood plasma, portal plasma, CSF, cerebrum, liver, kidney and skeletal muscle tissues in GalN-FHF. The skeletal muscle is found to constitute the greatest source of accumulated amino acids in FHF. The other tissues also contribute to the increased amino acids in the body as a whole. The increase in aromatic amino acids (AAA) tyrosine, phenylalanine and free and total tryptophan were the most striking among all the amino acids, including branched chain amino acids (BCAA), in all the tissues studied. The molar ratio of BCAA/AAA was found significantly reduced in all the tissues studied. $ gamma$-amino butyric acid was found significantly increased in the cerebrum and the brain stem. Most of the increased tryptophan in plasma, and almost 100% of the increased tryptophan in the brain were in the free form (non-protein bound). The increase in tyrosine concentration in plasma was closely correlated with tyrosine in the brain. Hemoperfusion using collodion coated activated charcoal (CAC) significantly reduced a number of aromatic amino acids in the plasma. This was followed by a significant reduction of the AAA in CSF, but not in the brain, of GalN-FHF rats. Hemoperfusion using tyrosinase immobilized within artificial cells selectively reduced tyrosine in the plasma but did not influence the tyrosine level in the brain. Hemoperfusion procedures resulted in a high plasma clearance for the aromatic amino acids. The results also suggested the loss of the blood brain barrier for amino acids across the capillaries. However, transport mechanisms between brain cells themselves and interstitial fluid seems to be maintained. / The buildup of middle molecular metabolites (MW 500-2,000) was demonstrated as the elevation of middle molecule peak 7g in the plasma and brain extract samples from GalN-FHF rats using serial liquid chromatography. CAC hemoperfusion significantly reduced the levels of 7g fraction in both plasma and brain extract samples. The fraction of subpeak 7g was found to contain peptidic substances. SDS-polyacrylamide gel electrophoresis further revealed the peptide nature of some of the middle molecule substances. The estimated molecular weight of these peptides was in the range of 1,300 and 1,400. Radioimmunoassay study indicated the increase of substance P (MW 1,345) in the plasma of GalN-FHF rats.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70360 |
| Date | January 1985 |
| Creators | Shi, Zhi Qing. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000400321, proquestno: AAINN75899, Theses scanned by UMI/ProQuest. |
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