582 G ASTRO-INTESTINAL "AUTOINTOXICATION" 



from tryptophane only through putrefaction, and not in cellular me- 

 tabolism. Other experiments support the same view.^^ However, 

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

 ditions associated with gangrene, putrid cancers, putrid placentas, 

 or putrid 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 Hei'ter^^ 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 confusion; 

 the continued absorption of enough indole to cause a constant strong 

 reaction for indican in the urine is sufficient to cause neurasthenic 

 symptoms. Long-continued injection of indole leads to hypertrophy 

 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 indole, 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 insignificant in proportion to the above- 

 mentioned doses that were found necessary to produce symptoms, 

 that we may well doubt the occurrence of noticeable intoxication 

 from this substance under ordinary conditions. Nesbitt*^ states that 

 twenty times as much indole or skatole as are excreted daily by an 

 adult man may be injected into the jugular vein of a dog of four 

 kilos without causing appreciable effects. Richards and Howland, 

 however, have demonstrated the possibility, that defective oxidation 

 of substances of this group may permit of intoxication. ■'■' When 

 subcutaneously injected, dissolved in oil, indole and skatole have the 

 property of greatly stimulating epithelial proliferation, similar to the 



'« See Scholz, Zeit. physiol. Chein., 1903 (38), 513; Undcrhill, loc. cil. Sherwin 

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

 fast (Biochem. Bull., 1914 (3), 41G). 



" Jour. Biol. Cheiii., 1907 (2), 575. 



'* See Distaso and Sugden, Biochem. Jour., 1919 (13), 153. 



'» New York Med. Jour., 1898 (l58), 89. 



" Woolley and Newhurgh, Jour. Amor. Med. Assoc, 1911 (50), 1790. 



^1 See Steenhuis, Folia Mikrohiol., 1915 (3), 70. 



"Jour. Amer. Med. Assoc, 1900 (-40), 1499. 



^' Jour. E.xper. Med., 1899 (4), 5. 



*" See note in Science, 1906 (24), 979. 



