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A competitive protein binding assay with a sensitivity of 80 picograms has been developed for 1alpha,25-dihydroxyvitamin D(3), the hormonal form of vitamin D(3). lalpha,25-Dihydroxyvitamin D(3) displaced tritiated hormone from a cytosol-chromatin receptor preparation isolated from chick small intestine, providing a simple assay for the hormone. The concentration of lalpha, 25-dihydroxyvitamin D(3) in human plasma, as determined by this assay, is approximately 6 nanograms per 100 milliliters; in patients with renal disease the concentration of this kidney-produced hormone is significantly lower.

The sulphonylureas are drugs of limited efficacy with fairly frequent, although usually reversible, adverse effects. Being highly protein bound, these drugs are subject to potential displacement interactions, which when combined with inhibition of their elimination, may result in profound hypoglycaemia. Due to hepatic metabolism and renal excretion of the parent drug and/or active metabolites, these agents are contraindicated in patients with liver or kidney disease. Oral hypoglycaemic agents are frequently used in elderly patients with limited vision and no dependable relatives, who cannot give themselves insulin. It is these patients--elderly, living alone in poor circumstances, often on several other medications, and possibly malnourished--who are at greatest risk for catastrophic hypoglycaemia with these drugs. Long acting agents like chlorpropamide and glibenclamide should be avoided in the elderly and in patients with irregular eating habits. Diet and exercise remain the primary modes of therapy of non-insulin-dependent diabetes mellitus. With careful patient selection and attention to drug and disease interactions, the sulphonylureas may be a useful adjunct to diet in treating a small proportion of insulin-resistant (so-called adult onset) diabetics. Patients most likely to respond to sulphonylureas are over 40 years old, mildly to moderately obese, have had diabetes for less than 5 years, and have never exhibited ketosis. There is no indication for simultaneous use of sulphonylureas and insulin. With both insulin and the oral hypoglycaemics alcohol is the agent most commonly implicated in lethal interactions.

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Background: Deleting the acetyl-CoA carboxylase 2 gene (ACC2) in mice results in continuous fatty acid oxidation. Results: Less fat accumulates in the liver, despite up-regulation of the de novo lipogenic pathway and dietary induction of fatty liver. Conclusion: Continuous fatty acid oxidation results in a futile metabolic cycle. Significance: ACC2-specific inhibitors could be a viable treatment against fatty liver disease.

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