An in vitro system has been developed to study N-acetyltransferase (NAT) activity using human liver slices in dynamic organ culture. Acetylation of para-aminobenzoic acid (PABA) and sulfamethazine (SMZ) in the presence of human liver slices was monitored by measuring the disappearance of the parent amine from the incubation medium using the colorimetric procedure of Bratton & Marshall. Presence of the acetyl conjugate was confirmed using HPLC. PABA acetylation rates varied from 0.72-2.52 nmoles/hr/mg protein (n = 8). This small variation (4 fold) is consistent with the classification of PABA as a monomorphic substrate. The variation in the rate of SMZ acetylation was greater than 20 fold (0.144-3.68 nmoles/hr/mg protein; n = 9). This larger variation is characteristic of SMZ as a polymorphic substrate. The results obtained indicate that human liver slices in dynamic organ culture can be used for the determination of hepatic NAT activity and acetylator status of individual human livers.

No description available.

Thesis(MAppSc)--University of South Australia, 1999

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

No description available.

No description available.

The pro-opiomelanocortin (POMC) prohormone produces several biologically active peptides, including £\-melanocyte-stimulating hormones (£\-MSH, £]-MSH, £^-MSH), corticotrophin (ACTH) and £]-endorphin. POMC-expressing neurons in the brain play a major role in the control of pain, energy homeostasis, pigmentation, adrenocortical function, and sebaceous gland lipid production. Recently, the peripheral POMC system is under active investigation to delineate their pathogenic roles in metabolic diseases such as Cushing¡¦s syndrome and obesity. In the present study, we employed adenovirus gene delivery system to achieve POMC overexpression in the livers of adult C57/BL6 mice. In the endocrine system of adrenal glands, hepatic POMC overexpression mice display hypertrophy the ACTH levels elevated concentrations in the blood, the ACTH receptor, melanocortin type 2 receptor (MC2-R) were decrease. This phenomenon explained the local adrenal gland tissue was inhibiting and feedback from central hypothalamic-pituitary- adrenal axis. Meanwhile, we investigated the islets of Langerhans in hepatic POMC overexpression mice, the insulin were disappear but the glucagon were constant, these reflect the blood sugar were loss of balance, maybe progress to metabolic syndrome. Subsequently, hepatic POMC overexpression resulted in liver injuries that the ALT and AST levels were significantly higher, the fat accumulation in the liver and the glycogen were diminished to nearly 1/4 of basal levels. Evidence the hepatic POMC overexpression induced inflammatory and fatty changes in the livers of mice. In summary, POMC gene delivery induces systemic POMC overexpression and results in fatty liver and adrenal dysfunction, which may facilitates a mice model for Cushing¡¦s-like metabolic syndrome.

No description available.

Thesis (MAppSc in Pharmacy)--University of South Australia, 1996

Thesis (Ph.D.)--University of Western Australia, 2006.