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THE EFFECT OF DIFFERENT HORMONAL CONDITIONS ON THE CONCENTRATION AND OXIDOREDUCTION STATE OF THE NICOTINAMIDE NUCLEOTIDES OF RAT LIVER.

1. The concentration and oxidoreduction state of the liver nicotinamide nucleotides of rats subjected to a number of hormonal treatments have been measured. 2. Adrenalectomy decreases the NADP(+) content by 80% but has little effect on NAD(+), NADH or NADPH. High doses of cortisone produce similar changes, but more physiological doses (5mug. daily) tend to increase the NADP(+) content. 3. Glucagon treatment of normal rats lowered the NADH and NADP(+) concentrations but did not affect the total amounts present. Growth hormone increased the concentrations and total amounts of NAD(+) and NADH but significantly decreased the concentrations and total amounts of NADP(+) and NADPH. 4. Measurements have been made of a number of enzymes in the livers of adrenalectomized and glucagon-treated rats that could affect the oxidoreduction state of NADP. The activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase are not affected by adrenalectomy or treatment with cortisone or glucagon. Nor does adrenalectomy affect the activity of NADPH-cytochrome c oxidoreductase or NADPH-glutathione oxidoreductase. The hepatic content of glutathione is, however, decreased 50% by adrenalectomy. 5. Measurements of the oxidation of [1-(14)C]glucose and [6-(14)C]glucose by liver slices from adrenalectomized rats showed that glucose oxidation was substantially normal, although phenazine methosulphate caused a smaller stimulation of the oxidation of C-1 of [1-(14)C]glucose in slices from the livers of adrenalectomized rats than it did with slices from controls. The hepatic synthesis of lipids from [1-(14)C]glucose was marginally increased in adrenalectomized rats. 6. The additional NADP(+) found when liver is extracted with 0.02n-sulphuric acid-0.1m-sodium sulphate is less affected than the NADP(+) extracted with 0.1n-hydrochloric acid in adrenalectomized or glucagon-treated rats. Hooded Norway rats appear to have less of this extra form of NADP(+) than albino rats. 7. An attempt has been made to correlate the observed changes in the nicotinamide nucleotides with metabolic patterns prevailing in different hormonal conditions.

Adrenalectomy↗

PROLONGED VITAMIN D INTOXICATION IN A PATIENT WITH HYPOPARATHYROIDISM.

Pitfalls in the management of hypoparathyroidism are illustrated by the case of a patient who developed hypervitaminosis D while receiving doses of calciferol and of calcium in amounts commonly recommended for treatment. Either the patient was very slow to obtain maximum vitamin D effect or else her sensitivity to vitamin D increased, because she did not become hypercalcemic until two years after treatment was started. The dose of vitamin D was halved to 50,000 units per day and the dose of calcium was lowered to 0.26 g. daily. She failed to remain under medical supervision for the next four years and presented with hypercalcemia and evidence of renal impairment. After vitamin D was discontinued she remained hypercalcemic for nine months.These findings are discussed in the light of current knowledge concerning the actions of parathyroid hormone and vitamin D. The influence of adrenocortical hormones on calcium metabolism is considered. The need to follow up hypoparathyroid patients closely, and to check the level of calcium in the serum, is emphasized.

Calcium↗