7should be looked for in such patients, since, if present, its correction might prolong life so that measures directed toward the underlying process of endotoxin shock could be effective.Summary. An immediate and progressive fall in blood glucose level occurs in CC14treated guinea pigs given a lethal dose of bacterial endotoxin. The hypoglycemia is evidently due to a decrease in rate of hepatic glucose production. Maintenance of the blood sugar level appears to prolong survival but does not alter the extreme susceptibility of these animals to endotoxin. Hypoglycemia should be looked for in patients with severe liver disease who develop gram-negative bac-teremia, since if uncorrected it could render all other therapeutic measures ineffective.Oral administration of spironolactone,* a steroidal spirolactone ( 1 ) and an antagonist of the renal electrolyte effects of mineralocorticoids (2), produces measurable plasma concentrations of a fluorogenic, A6-metabolite (3), 3-(3-0x04 7P-hydroxy-4,6-androstadien-17~yl)propanoic acid lactone( 1 ) or aldadiene. Such data on plasma aldadiene have been applied in study of gastrointestinal absorption with various pharmaceutical preparations of spironolactone (3-7). I n both experimental animals and man, data have suggested a correlation of aldadiene titers with renal electrolyte manifestations after spironolactone administration(4,7). However, as aldadiene obtained synthetically also possess antimineralocorticoid properties ( 1,8), an important question relates to relative influence of the A6-metabolite on renal properties of spironolactone. As one approach, therefore, spironolactone and aldadiene were examined * 3 -( 3 -0xo-7a-ace tylthio-1 7p-hydroxy-4-androsten-17a-yl) propanoic acid lactone ; AldactoneB is the trademark of G. D. Searle and Co. for brand of spironolactone. comparatively in rats and dogs for plasma aldadiene levels and urinary electrolyte effects; some data believed to be pertinent to the question are summarized below.Material and methods. In rats (175-225 g) , spironolactone or aldadiene was orally administered concurrently with 12 pug of deoxycorticosterone acetate (DCA) subcutaneously, as solutions of corn oil. Four-hour samples of urine were collected in metabolism cages (4 rats/cage) in one series of animals for Na and K determination. Antimineralocorticoid activity of the spirolactones was assessed by reversal of the urinary Na/K response to DCA according to previously described procedures ( 2 ) . DCA alone induces Na retention and K loss, to produce thereby a reduction in the ratio of urinary Na/K. Other rats treated identically were sacrificed under ether at 1, 2, 3 and 4 hours after treatment, and blood specimens from the abdominal aorta collected in heparinized tubes using a plastic cannula. Plasma was separated by centrifugation for aldadiene analysis. Trained female mongrel dogs (14-19 kg)

Administration of DCA induced typical mineralocorticoid effects in a dog, namely the retention of urinary Na and Cl and the loss of K ions. Coadministration of spironolactone orally at several doses neutralized the effect on K, but produced a rate-limited inhibition of Na and Cl retention, by altering tubular reabsorption of the ions. Plasma levels of spironolactone did not appear to be a factor limiting the Na and Cl response. Interpretation of these data indicates that spironolactone inhibited only one of the tubular reabsorbing mechanisms for renal effects of DCA.

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