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Biomedical subjects

D Weir

Publications and source records attributed to D Weir.

44 records · Page 3Linked to original sources

Effect of anticonvulsant drugs on the rate of folate catabolism in mice.

An increase in folate catabolism has been suggested as the cause of the folate deficiency observed in many clinical conditions, including chronic anticonvulsant therapy. Previous studies have shown that the radioactive catabolites, excreted after an equilibration period of 3 d, consisted exclusively of folates that had been cleaved to produce pteridines and p-aminobenzoylglutamate, most of which was excreted as acetamidobenzoylglutamate. We have developed an experimental animal model using mice to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of [3H]p-aminobenzoylglutamate and [3H]acetamidobenzoylglutamate in urine. Administration of diphenylhydantoin at three different doses (0.5, 20, and 50 mg/kg) significantly increased the rate of catabolism as measured by an increase in both the mean daily excretion and the cumulative excretion of these catabolites. Administration of intramuscular phenobarbitone on the other hand, did not affect the rate of catabolism, when compared with controls.

Animals↗

Angiographic evaluation of gastrointestinal haemorrhage complicating pancreatic disease.

Seven patients with gastro-oesophageal varices due to splenic or portal vein obstruction from a diseased pancreas have been seen at the Mater Hospital during the past three years. Four of these patients had episodes of acute and massive gastrointestinal bleeding and this paper emphasises the role of angiography in the management of this complication. In three instances the bleeding was the result of the varices, but in one patient with carcinoma of the head of the pancreas the bleeding was shown to result from invasion of the tumour into the duodenum.

Adult↗

The occurrence of folate-derived pteridines in rat liver.

1. It has previously been shown that folate polyglutamates in the rat are catabolized almost exclusively via cleavage of the C-9--N-10 bond, resulting in the formation of pteridines and p-aminobenzoylglutamate. The latter catabolite is rapidly excreted, appearing in the urine as acetamidobenzoylglutamate and is undetectable in rat liver. 2. The pteridines catabolites on the other hand are retained to a much greater extent by the liver, forming an ever-increasing proportion of the retained radioactive tracer. 3. A possible role for these pteridines as cofactors in brain metabolism is discussed.

Animals↗

The fate of folate polyglutamates in meat during storage and processing.

The rate of hydrolysis of chicken liver folate polyglutamates, by endogenous liver conjugases, under various conditions of storage, heat, and tissue disruption, were investigated. The procedure used was to allow a radioactive tracer dose of the vitamin to equilibrate into the folate polyglutamyl pool. After various storage periods and treatments the polyglutamyl state of the folate present was examined by analytical techniques based on oxidative degradation of native folate polyglutamates to the corresponding p-aminobenzoylpolyglutamate followed by chromatographic separation on DEAE cellulose anion exchange resin. Identification of folate polyglutamates present was made by simultaneous elution of known p-aminobenzoylpolyglutamate markers. In an intact tissue sample only slight degradation was found after 48 hr at 4 C; complete degradation of folate polyglutamates taking 120 hr. Samples of homogenized tissue show complete degradation to folate monoglutamates and a small amount of diglutamate after 48 hr storage. Superimposed on the above is the consideration that if at any time prior to or during storage the liver is heated to greater than 100 C irreversible inactivation of the endogenous conjugases takes place and the folate polyglutamate pattern is stabilized. It was also demonstrated that during two different heating procedures no extra deconjugation occurred.

Animals↗