In a previous report (1) were described the results of experiments in which isotopic uric acid was injected intravenously into normal and gouty human male subjects. The purpose was to ascertain the magnitude of the "miscible pool," that quantity of uric acid present in the body capable of prompt mixing with the injected material, and the rate of its turnover. The results indicated that there are some 1200 mg. of miscible uric acid normally present, a finding in accord with that of Geren and associates (2), that between 50 and 75% of this is each day replaced by newly formed uric acid and that this latter quantity exceeds the quantity excreted daily in the urine, suggesting the occurrence of limited catabolism of uric acid in man. In the gouty subjects studied, the magnitude of this miscible pool exceeded the normal levels by as much as 15 fold. Indeed, so large was the quantity of promptly miscible uric acid as to indicate that at least a portion of this material must reside in the solid phase rather than in solution in body fluids.In the present study 2 we have extended our observations on the amount and distribution of miscible uric acid in the gouty patient and have investigated the effects upon these quantities of some of the therapeutic agents commonly employed in this disease. The effect of ACTH 3 on the normal subject has also been studied.
MATERIALS AND METHODSThe preparation of isotopic uric acid labeled in the one and three positions with N', the isolation of uric acid 1This study was aided in part by grants from the Division of Endocrinology, the United States Public Health Service, and Armour and Co. 2 preliminary report of this work has appeared (3). 8We are indebted to Dr. John R. Mote, Medical Director, the Armour Laboratories, Chicago, for the ACTH used in these studies. from the urine samples and isotope analysis have all previously been described (1). The only novel chemical procedure was the analysis of a tophus excised from subject A. L. on the ninth day of his third experiment. This specimen when dried in vacuo over P205 weighed 6.8 gm.In the expectation of dissolving successive laminae of uric acid, the tophus was then placed in the thimble of a Soxhlet apparatus over boiling water and extracted for three periods of 24 hours each, the contents of the flask being replaced by fresh water after each period. An aliquot of each extract was analyzed for uric acid by the method of Forsham and co-workers (4) and pure uric acid was isolated from the remaining extract for isotope analysis by the same method previously employed in the isolation from urine (1). The residue of the tophus was boiled in 500 ml. of 0.07 M Li2COa for one hour, the solution filtered, and analyzed for uric acid. The same mathematical treatment of results has been employed as was described in the earlier report (1).Both the normal and gouty subjects were maintained in slightly positive nitrogen balance on constant diets calculated to contain purines equivalent to 2.4 to 3.1 mg. of uric acid per day. It was found that a prelimi...