every 2 months to a maximum of 100 mg/day. He noted clinical improvement with 1 5 mg, but said it was less rapid than that with 50 and 100 mg/day. However, the clinical picture is not generally considered to be consistent enough to allow such fine discrimination in drug response, and in most clinical trials it has been found necessary to assess the drug by the bacteriologic response in groups of lepromatous cases, each group on a particular dosage for a year or more.Thus it seems indicated to test the therapeutic effect in human leprosy of lower dosages of DDS and less frequent administration.The margin between toxic level and therapeutic level of the drug appears to be so large as to allow considerable innovation in the regimen. DDS is excreted only slowly and Ross ( 15) has reported detectable concentrations in blood 2 to 4 weeks after the last administration of sulfone. The results suggest that DDS might have an especially useful role in chemoprophylaxis, a contra1 measure potentially adaptable to many leprosy endemic areas.Summary. 1. The activity against Mycobacterium Zeprae of 4,4'-diaminodiphenyl sulfone (DDS) was tested in mice by feeding a series of diets containing the drug in concentrations ranging from 0.03 to 0.00001%.
Multiplication of M . Zepae was completelysuppressed a t all levels. 2. The lowest DDS intake was a hundred times less that the least amount required to produce chemically detectable amounts in the blood (0.2 to 0.3 p,Lg/ml) * 1. Lowe, J., Leprosy Rev., 1954, v25, 113.
A technique for measuring the action of small doses of ACTH on the oxygen consumption of slices of cattle adrenal cortex is described.The oxygen consumption rate of such slices in vitro is increased by ACTH. A linear relationship between logarithm of the dose of ACTH and the percentage increase in the rate of oxygen uptake is obtained with this method, and its suitability for biological assay purposes has been investigated.The question of the specificity of this action of ACTH is discussed.The energy metabolism of the adrenal cortex has been investigated by several workers in recent years. Carpenter, McLeod & Reiss [1946] found increased oxygen uptake values in the adrenal cortices of rats treated with ACTH. Gemzell [1948] and Reiss & J. M. M. Halkerston [1950] showed that treatment of rats with ACTH increased the phosphorylization rate of the adrenals. Tepperman [1950] using dog adrenal slices, Saffran, Bayhss & Webb [1951] bisected rat adrenals and Ferstl, Heppich & Schmid [1951] cattle adrenal cortex shces, demonstrated that ACTH added to the incubation medium brought about an in¬ crease in oxygen uptake and a decrease in the ascorbic acid content of the tissues used.Overbeek & van der Vies [1952] reported that the increase in oxygen consumption rate and decrease in ascorbic acid content of surviving adrenal cortex slices found in vitro experiments was not a specific effect of ACTH, as preparations inactive in the adrenal ascorbic depletion test [Sayers, Sayers & Woodbury, 1948] showed the same ability to increase the oxygen-uptake rate as active preparations.However, a direct action of ACTH on surviving adrenal tissue has been shown by Vogt [1951] and Pincus, Hechter & Zaffaroni [1951], using the isolated perfused gland; by Saffran, Grad & Bayliss [1952] and Haynes, Savard & Dorfman [1953] using bisected rat adrenals and cattle adrenal cortex slices respectively. The action was demonstrated by increased hormone production as estimated by biological assay, chemical analysis or radioactive isotope techniques. This report describes an improved technique for assessing the effect of different substances on the respiratory metabolism of surviving adrenal cortex tissue. The technique has been apphed to a study of the action of ACTH on such tissue and the relation between the in vivo activity of ACTH and the in vitro effect.
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