Burian and Schur3 also established the fact that while the endogenous uric acid elimination varied between 0.3 and 0.6 gram daily, according to the individual, it did not vary in the same individual, but was a constant factor in his metabolism.

A purin-free diet is obtained by giving such articles of food as milk, eggs, bread, potatoes, fats, and sugars, none of which contain nuclear material which forms exogenous purins in the body. Burian and Schur found that on such a diet the uric acid elimination was entirely independent of the quantity of protein ingested. It has been demonstrated by Rockwood1 that the endogenous uric acid elimination is independent of the calorific value of the diet. Addition of 500 calories contained in maple sugar to a diet containing 2500 calories did not affect the excretion of uric acid. Rock wood's experiments extended over a long period of time. His individuals were nourished on milk, eggs, white bread, crackers, cheese, apples, and butter. The constancy of the uric acid output in the same individual is seen in the following table - in one case the record covering nearly a year:

3 Burian and Schur: "Pfluger's Archiv," 1901, lxxxvii, 239.

Table Showing The Constancy Of The Daily Endogenous Uric Acid Excretion In The Same Individual (Two Subjects)

This total shows the constancy of the output of endogenous uric acid in the same individual during a long period. Here the difference in the behavior of two individuals may be ascribed to a personal idiosyncrasy as regards the capacity of producing uric acid. From the record of Chittenden's2 experiments, which covered a period of twenty-one months, it may be observed that a very low protein diet and moderate intake of food were without effect on the output of uric add.

The source of the endogenous purins has been the cause of considerable speculation. In birds there is a large synthetic production of uric acid in the liver, for Minkowski1 has shown that extirpation of the liver in geese leads to a replacement of uric acid by ammonia and lactic acid in the urine. The following analyses2 give an idea of the composition of the urine of birds:

1 Rockwood: "American Journal of Physiology," 1904, xii, 38. 2 Chittenden: "Physiological Economy in Nutrition," 1904, p. 24.

The method of the synthetic production of purins is entirely conjectural.

Ingestion of pyrimidin bases (p. 528) has failed to yield purins in the organism.3

Burian4 has investigated the source of the endogenous purins and comes to the conclusion that only a small part of the endogenous uric acid arises from the nucleoproteins of cellular tissue or those of dead leukocytes. It would require too large a destruction of tissue to provide from 0.3 to 0.6 gram uric acid or 0.1 to 0.2. gram purin nitrogen daily in the urine if it all arose from cell nuclein.

Burian and Schur's5 analyses, showing the content of purin nitrogen in various tissues, are given below:

Table Showing The Quantity Of Purin N Contained In 100 Grams Of Different Animal Tissues

1 Minkowski and Naunyn: "Archiv fur experimentelle Path, und Pharm.," 1886, xxi, 41.

2 Szalagyi and Kriwuscha: "Biochemische Zeitschrift," 1914, lxvi, 126. 3 Steudel: "Zeitschrift fur physiologische Chemie," 1903, xxxix, 136.

4 Burian: Ibid., 1905, xliii, 532.

5 Burian and Schur: "Pfluger's Archiv," 1900, lxxx, 308.

To obtain the amount of endogenous uric acid present in the urine, if it were produced by the destruction of nucleo-proteins, it would be necessary to destroy completely a quantity of nucleoprotein equal to that contained in more than 100 grams of liver. It does not seem possible that nuclein destruction or nuclein metabolism could reach this extent.

Burian concludes that in the resting muscle there is a constant production of hypoxanthin which is converted into uric acid through the activity of the xanthin oxidase. In the active muscle there is a greater production of hypoxanthin which is not completely oxidized on account of a local oxygen deficiency.

It had been found by many previous observers that exercise has no effect on the purin excretion in the urine of twenty-four hours in man. Burian, however, finds a large increase in the purin elimination for an hour or two after severe muscular exercise, and this is followed by a compensatory reduction in the output during those subsequent hours which represent the interval of weariness in the muscle.

These observations were confirmed by the work of Rock-wood,1 who saw that the purin excretion was less during the night than during the day, and by the work of Pfeil,2 who found a constant morning rise in the output of purins in human urine.

These facts confirm Burian's contention that the most general source of endogenous purins is a constant production of hypoxanthin in muscle, a production which varies with the individual and is possibly proportional to the mass of his musculature. Comparable to this is the constant production of creatinin (p. 209). Such of the purin bases as escape oxidation may be excreted by the blood flowing through the kidney even as uric acid is excreted under the same circumstances.

Siven3 does not believe that muscular work appreciably raises the production of endogenous purins. He thinks that the reduction in purin elimination during the night time is due to general inactivity of all the tissues, and shows that when an evening meal containing much protein is taken and the kidney is made thereby to functionate during the night, then the purin elimination is increased. Burian's discovery of increased elimination during work was perhaps due to the fact that the work was accomplished during the morning hours, when an increased elimination due to purins retained during the night would normally occur.

1 Rockwood: Loc. cit.

2 Pfeil: "Zeitschrift fur physiologische Chemie," 1904, xl, 1.

3 Siven: Abstract in "Zentralblatt fur Stoffwechsel," 1906, i, 81.

Mendel and Brown1 have determined the hourly excretion of uric acid as influenced by the ingestion of meat, liver, and other animal tissues. The increase in the eliminated uric acid is very marked and reaches a maximum two or three hours after the ingestion of these animal tissues. Thus after the ingestion of 600 grams of chopped meat the uric acid elimination, which had been 19 milligrams, rose during the following three hourly periods to 28, 88, and 98 milligrams, and then fell in successive hours to 79, 73, 51, 36, 25, and 22 milligrams. It will be seen later that such curves of exogenous uric acid excretion do not occur in the gouty patient in whom there is uric acid retention (see p. 548).

The recent studies of Stanley Benedict2 concerning the uric-acid content of the blood have brought to light some new and important facts. Fowl's blood had heretofore been accounted much richer in uric acid than ox blood. Benedict finds this to be true only of the blood-serum, which in the fowl contains uric acid which circulates uncombined, whereas the blood-serum of the ox is almost entirely free from uric acid. Considered as a whole, however, ox blood yields 0.50 milligram of uncombined uric acid in 100 c.c. of blood. This is the amount which had been previously reported, but after hydrolysis 6.7 milligrams of uric acid were isolated and identified. This is entirely contained in the corpuscles and amounts to 50 per cent, more than the uric acid content of chickens'blood. These results throw additional light upon Minkowski's conception of the nature of gout, soon to be considered.

1Mendel and Brown: "Journal of the American Medical Association," 1907, xlix, 896.

2 Benedict, S. R.: "Journal of Biological Chemistry," 1915, xx, 633.