576 GASTRO-INTESTINAL "AUTOINTOXICATION" 



although proteoses are distinctly toxic. This last statement has been 

 much contested, because the difficulty of purifying proteoses ob- 

 tained from ordinary sources has left open the possibility that such 

 toxic effects as have been observed are due to contaminating sub- 

 stances, such as histamine, and not to the proteoses themselves. More 

 recent work, however, particularly that of Underhill,- Gibson' and 

 Zunz,* seems to have established affirmatively the toxicity of proteoses, 

 whether from animal or vegetable proteins. Besides the classical 

 effect of inhibiting the coagulation of the blood, the proteoses have a 

 lymphagogue effect (Heidenhain),^ cause a marked febrile reaction,^ 

 and in doses of some size are fatal to experimental animals (rabbits 

 being much less susceptible than dogs and many other animals). 

 Locally they cause a mild inflammatory reaction, which is 

 followed by the appearance of much connective-tissue formation.^ 

 Long continued injection of proteoses does not produce visceral 

 lesions.* The careful sfudies of Zunz show that intravenous injection 

 of hetero-albumose, thio-albumose, deutero-albumose and proto- 

 albumose cause a rise in blood pressure, but large doses may cause a 

 fall in pressure; the abiuret products of tryptic digestion are much more 

 actively depressor than the albumoses. As a general rule, however, 

 it has been observed that the first products of protein hydrolj^sis are 

 the most toxic, and with further cleavage the toxicity lessens and 

 finally disappears, as shown especially in the studies on anaphylaxis 

 and anaphylatoxin formation.^ Thus Wolf^° found that the amino- 



2 Amer. Jour. Physiol., 1903 (9), 345; Jour. Biol. Chem., 1915 (22), 443 (litera- 

 ture). See also Hanke and Koessler on the relation of histamine to peptone shock. 

 Jour. Biol. Chem., 1920. 



3 Philippine Jour. Sci., 1914 (9), 499. 



* Arch, inter nat. physiol., 1911 (73), 110. 



5 See also Nolf, Arch, inter nat de Physiol., 1906 (3), 343. 



* Gibson finds that carefully purified proteoses have but a slight pvrogenic ef- 

 fect. (Philippine Jour. Sci., 1913 (8), 475.) 



' In a paper appearing in the Transactions of the Chicago Pathological Society, 

 1903 (5), 240, I published the observation that repeated injections of Witte's 

 "peptone" (which consists chiefly of proteoses) into rabbits led to the production 

 of marked cirrhosis of the liver, and suggested the possibility that proteoses 

 escaping through a diseased gastric or intestinal wall into the blood might be 

 a factor in the production of cirrhosis in num. Subsequent observations, how- 

 ever, have shown that repeated injection of almost any foreign protein material 

 (e. g., emulsions of organs, foreign blood, etc., used in immunization experiments) 

 will cause a similar cirrhosis in rabbits, which animals, indeed, often spontaneously 

 show this condition when apparently otherwise normal. " Peptone" injections in 

 dogs and guinea-pigs have tailed to cause a similar cirrhosis, and hence the value 

 of these and all other rabbit experiments on cirrhosis of the liver is very question- 

 able; however, the possibility of the correctness of the original conclusions still 

 remains open. 



» Wool ley e/ aZ., Jour. Exp. Med., 1915 (22), 114. Boughton describes acute 

 degenerative changes from Witte's peptone. (Jour. Immunol., 1919 (4), 381.^ 



" The statement of v. Knafii-Lcnz (Arch. exp. Patii. u. Pharm., 1913 (73), 

 292) that the toxicity of the cleavage products varies directly with their trypto- 

 phane content could not be corroborated by Underhill and llendrix, Jour. Biol. 

 Cliem., 1915 (22), 443. 



'» Jour, of Physiol., 1905 (.32), 171. 



