570 ABNORMALITIES IN METABOLISM 



seems very probable that substances more toxic than the above- 

 mentioned acids are involved. Weichardt^* claimed that he had de- 

 monstrated a toxic substance, produced by muscular fatigue, which 

 in structure resembles the bacterial toxins, called by him kenot ox in, ^^ 

 and against which an antitoxin may be obtained. This toxic material 

 is, he believes, formed from the protein molecule in the first stages of 

 its decomposition, as a side product which is normally protected against 

 by a formation of an antitoxin, rather than by being split up further, 

 as is the case with the rest of the protein molecule. The study of 

 anaphylaxis has led to so many evidences of the remarkable toxicity 

 of the products of protein cleavage, that the possibility that some of 

 these may be responsible for fatigue cannot be entirely disregarded 

 at present, ^^ although Lee and Aronovitch^^ could not demonstrate 

 toxic substances in fatigued muscles, and no one has been able to 

 confirm Weichardt's specific findings. The following observation of 

 Mosso indicates that the blood of fatigued animals contains toxic 

 substances: If blood is transfused from an exhausted dog to a normal 

 dog, from which an equivalent amount of blood has been withdrawn, 

 this second dog will show the usual manifestations of fatigue. Men- 

 denhalP^ has found that the heart is also affected by the products of 

 muscular fatigue. Recent studies in shock (Bayliss, Cannon) attrib- 

 ute the manifestations of shock, at least in part, to toxic cleavage 

 products of injured tissues, and many of these manifestations are 

 allied to fatigue. 



Mental Fatigue. — The chemical changes of mental fatigue are not 

 kno'wn, but the ganglion-cells show marked structural alterations 

 as a result of fatigue, chromatolysis often being very striking. Since 

 lecithin forms so important a part of the nervous system, it is tempting 

 to imagine that in fatigue excessive quantities of its toxic decomposi- 

 tion-product, choline, and the still more toxic derivative of choline, 

 neurine, are formed in considerable amounts and cause part, at least, 

 of the intoxication. 



That choline or neurine actually are the cause of any of the symp- 

 toms of fatigue, however, has not been established; but Donath^^ 

 considers choline an important factor in the production of epileptic 

 convulsions ^^ Animals kept for a long time from sleeping are said to 

 show the presence in their blood, cerebro-spinal fluid and brain tissues, 

 of a poisonous property causing somnolence in other animals (Legendre 



'■' " Ueber Ermiidungsstoffe, " Enke, Stuttgart, 1912; KoUe and Wassermann's 

 Handbuch, 1913 (2), 1499. 



"* Hec Woichardt and Schwenk, Zeit. physiol. Chcm.. 1913 (83), 381. 



" The failure of various investigators to corroborate \A'cichardt is discussed by 

 Konrich, Zeit. f. Hyg., 1914 (78), 1; Ivorff- Petersen, ibid., p. 37. 



1' Proc. Soc. Exp. Biol. Med., 1917 (14), 153. 



»« Amer. .lour. Physiol., 1919 (48), 13. 



"• Zeit. phy.siol. Chem., 1903 (39), 52(5. 



'" Concerning the theories and literature of the subject of epilepsy in relation 

 to its pathologieal chemistry and to autointoxication, sec the review of Masoin. 

 Arch, internat. de Pharmacodynamie, 1904 (13), 387. ' 



