464 THIAMINE 



Von Muralt proposes that as long as this uncertainty exists this substance 

 be called "the second Vagusstoff," because Loewi, before he understood the 

 exact nature of the chemical mediator in the heart, called it "Vagusstoff." 



Thus we have two well-established facts concerning the pathology of 

 thiamine in animals. The first is the activity of thiamine pyrophosphate 

 as a coenzyme in the carbohydrate metabohsm; the second is the role of 

 thiamine or a derivative of thiamine (the "second Vagusstoff") on the 

 neurophysiological activity. We do not yet know whether these facts are 

 closely connected, or whether they are quite independent from each other. 

 From the fact that the thiamine pyrophosphate lacks the neurophysiological 

 action of thiamine it is probable that the neurophysiological activity is dif- 

 ferent from the activity on the carbohydrate metabolism. 



On the other hand we know that thiamine pyrophosphate is active in 

 the production of acetic acid which is essential to restore the active acetyl- 

 choline from the inactive choline that is formed from acetylcholine by the 

 action of the cholinesterase. 



C. IN MAN 



In the beginning of vitamin research it was easy to compose a diet for 

 the study of thiamine deficiency. With fowls or pigeons as experimental 

 animals, polished rice, after being washed in running water to remove the 

 last traces of thiamine, was a suitable diet. Polished rice, however, not only 

 lacks thiamine, but it also shows a shortage of many other nutrients. There- 

 fore when other experimental animals, e.g., rats, were used, it appeared 

 necessary to add these other nutrients (proteins, mineral salts, nearly all 

 other vitamins) or to compose a complete, synthetic diet. 



Williams et al.,^* in their experiments to investigate the signs of a pure 

 thiamine deficiency in volunteers on a thiamine-poor diet, found no signs 

 of edema in their experimental persons, whereas the natives in rice-consum- 

 ing countries recognize beriberi because of the signs of edema in these 

 patients. 



Therefore, to study the effects of a pure thiamine deficiency it is neces- 

 sary to provide a diet that contains all nutrients in physiological amounts, 

 except thiamine. Since we do not yet know all the essential nutrients, it is 

 very difficult to compose a suitable synthetic diet, not considering the cost 

 of some nutrients ! So it is better to choose a good natiu'al diet in which only 

 the thiamine is destroyed. In these diets the thiamine is often desti-oyed 

 by autoclaving for several hours at pH 5. But by this procediu'e other rni- 

 trients are damaged too. A more specific way to destroy the thiamine is to 



" R. D. Williiims, H. I.. Mason, H. F. Smilli, and U. M. Wihl(M-, Arch. Internal Mai. 

 69, 721 (1942). 



