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Biochemical studies of thiamin deficiency in the lamb

Thornber, Elizabeth Joy (1979) Biochemical studies of thiamin deficiency in the lamb. PhD thesis, Murdoch University.

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Abstract

Severe thiamin deficiency was produced in lambs and an assessment made of the suitability of the thiamin-deficient lamb for studying the changes occurring in the disease polioencephalomalacia (PEM). As the disease occurs sporadically it is advantageous to develop experimental models. Current models involve dosage of sheep or cattle with an antimetabolite of thiamin and the involvement of similar antimetabolites in field cases of the disease has been postulated. This thesis presents a model based on dietary lack of thiamin in young lambs. Polioencephalomalacia was produced in all lambs kept on the deficient diet for a sufficiently long period and clinical signs and lesions resembled those of naturally occurring polioencephalomalacia. Thus it is not necessary to postulate that the action of an antimetabolite of thiamin contributes to the development of field cases.

It was found that calcium and magnesium concentrations in the brain were not affected by thiamin deficiency in lambs, contrary to the situation in pigeons. There were also no significant changes in plasma levels of sodium, potassium, calcium or magnesium. However, erythrocyte transketolase activity dropped to low levels in deficient lambs while stabilizing at or above 100 micromoles sedoheptulose-7-phosphate per min per litre in thiamin-supplemented pair-fed controls.

The concentrations of unphosphorylated thiamin (T), thiamin monophosphate (TMP), thiamin diphosphate (TDP) and thiamin triphosphate (TTP) were measured in three areas of brain ((1) an area of grey matter in the cerebral cortex where PEM lesions commonly occur, (2) an area of grey matter where lesions rarely appear, and (3) unaffected white matter) at three different times during the development of deficiency. In the thiamin-deficient lambs, TTP was maintained at normal concentration while the concentration of unphosphorylated thiamin, TMP and TDP decreased markedly, particularly in grey matter (areas 1 and 2). The mean concentration of TDP (one of the two biologically active forms of thiamin) in grey matter decreased to 22 per cent of control values after four weeks on the deficient diet. These results are similar to reported findings in thiamin-deficient rats where TDP decreased to 26 per cent of control values in the most susceptible area of the brain of symptomatic animals.

They contrast with measurements made in children who died of subacute necrotizing encephalopathy where affected regions of brain had a decreased proportion of TTP and an increased proportion of TDP.

The arterio-venous differences across the brain in glucose. D-3-hydroxybutyrate, glutamate and glutamine concentrations were measured. There were no statistically significant differences between thiamin-deficient and control values.

The disappearance of a single intravenous dose of 35S-thiamin from the plasma was studied in thiamin-deficient and control lambs. The shorter half-time for the disappearance in deficient lambs reflected the expected avidity of deficient tissues for the vitamin.

This thesis has extended the understanding of thiamin deficiency in the lamb and shown that the thiamin-deficient lamb may be used as a model for the field disease of polioencephalomalacia, without recourse to dosage with antithiamin compounds.

Item Type: Thesis (PhD)
Murdoch Affiliation: School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: repository@murdoch.edu.au. Thank you.
Supervisor(s): Dunlop, Robert and Gawthorne, Jeffrey
URI: http://researchrepository.murdoch.edu.au/id/eprint/53215
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