574 GASTRO-INTESTIXAL '■AVTOiyTOXICATlOX" 



aiipear in tlie urine. -■' Whether i)art of tlie urinary indiean is derived 

 from tryptophane liberated during intracellular protein metabolism, 

 and not from intestinal putrefaction, has long been a disputed point 

 among physiological chemists.-" The demonstration hj Ellinger and 

 Gentzen -' that try]ito])hane, when fed or injected su1)cutaneously, 

 causes no increase in uriiuiry indican, whereas its injection into the 

 cecum causes much indicanuria, would indicate that indole is formed 

 from tryptophane only through putrefaction, and not in cellular 

 nietabolisiu. Othei- expei'imeuts support the same view.-*^ However, 

 it is possible that part of the indican present in the urine during 

 conditions associated with gangrene, putrid cancers, putrid placentas, 

 or puti'id purulent exudates, may be derived from these decomposing 

 materials. The statement that indicanuria is of significance in in- 

 sanity could not be substantiated by Borden,-" who used quantitative 

 methods and careful controls. A large proportion of the data and 

 conclusions in the literature concerning indicanuria are valueless be- 

 cause of improper or inadequate methods. 



Probably the chief agent in the formation of indole in the intes- 

 tines and in putrid tissues is the colon bacillus, which, as is well 

 known, produces indole in ordinary culture-media. 



Toxicity of Indole. — Although the toxicity of indole seems to be 

 relatively slight, and this toxicity is further reduced by the conver- 

 sion of indole into indoxyl and indican, yet Herter ^^ found that ad- 

 ministration to healthy men of indole in quantities of 0.025 to 2 grams 

 per day caused frontal headache, irritability, insomnia, and confu- 

 sion ; the continued absorption of enough indole to cause a constant 

 strong reaction for indican in the urine is sutificient to cause neuras- 

 thenic symptoms. Long-continued injection of indole leads/to hyper- 

 trophy of the adrenal medulla and slight interstitial changes in the 

 kidneys,^^ but the reputed responsibility of indole for arteriosclerosis 

 is most doubtful. ^^^ Lee ^- has also demonstrated that iiulole. skatole, 

 and methyl mercaptan cause muscles to react to stimuli like fatigued 

 muscles. Normal urine contains but about 12 milligrams of indican 

 per day, which amount is so insigiiificant in proportion to the above- 

 mentioned doses that were found necessary to produce symptoms, 

 that we may well doubt the occurrence of noticeable intoxication 



-^' If frt'latin is subaiitutod for proteins in tlic diotary, indican is not oxrrcted, 

 because {gelatin does not contain tryptophane (Underliill, Amer. .lour. Piivsiol., 

 1!KM (VI), 17(i). 



20 Literature by Gerliardt, Erfrel). der I'liysiol., 1!)(I4 ( 11 [. Abt. T), LSI. 



27 TL)fineister's Beitr., 1903 (4), 17L 



2sSee Scliolz. Zeit. physiol. Clieni.. 1!)0.3 (.'JS), fiL'?; ITnderhill. Jor. cit. Slierwin 

 and Hawk found an absence of indican in the urine in tlie latter part of a long 

 fast (ISiocliem. Bull., 1914 (3), 410). 



2ft Jour. Uiol. Cheni., 1907 (2), r)75. 



30 X,.\v York Med. dour., 1S9S (6S), 89. 



31 W.xdlev and Xewburgb, .lour. Amer. IMed. Assoc. 1911 (oO), 1796. 

 siaSee Steenliuis, Folia Mikroliiol.. 1915 (3). 7(>. 



32 Jour. Amer. Med. .\ssoc., 190() (40), 149!t. 



