X. EFFECTS OF DEFICIENCY 465 



treat (he diet, or the thiaiiiiiie-containiiis parts of the diet, with sulfite.'^- "^ 

 Presuinal)ly the most specilic method ol" destroying the thiamine would l)e 

 treatment witii thiaminase. Smith and Proutf' stated that, eats fed a diet 

 consisting exehisively of thiaminase-rieh raw carp de\-eloped all the signs 

 of the thiamine deficiency characteristic foi- this animal. To counteract 

 specifically the activity of thiamine, the antithiamines, e.g., pyrithiamine 

 or oxythiamine, can be used. WooUey"* was able to demonstrate that at 

 least one of the activities of pyrithiamine consists in the antagonizing of 

 the synthesis of eocarboxylase — the active form of thiamine in carbohy- 

 drate metabolism. Woolley and White''-* state that, whereas mice fed a 

 ration free of thiamine de^'elop no characteristic symptoms of thiamine 

 deficiency, the same animals, on administration of pj'rithiamine, do show 

 many of these symptoms. Therefore the best way to study the effects of 

 uncomplicated thiamine defieiencj^ presumably is the use of antithiamines 

 and thiaminases, added to an otherwise optimal diet. A great difficulty is 

 the detection of the first signs of a deficiency. This is important because 

 b(Mil)eri is not found in Western countries, but it is possible that even here 

 many persons suffer from a mild thiamine deficiency. Usually the excretion 

 of thiamine into the urine per 24 hours is determined, or during 3 hours 

 after giving a measured dose of thiamine. Also the blood thiamine level is 

 used as a yardstick. However, this gives only a vague indication.-° Swank 

 and Jasper-^ compared encephalograms of normal pigeons with those of 

 thiamine-deficient birds. An increase in the brain potentials occurred slowly 

 in the thiamine-deficient pigeons and preceded the development of clinical 

 signs. Shortly before the appearance of preopisthotonus the amplitude of 

 the brain potentials became three times as high as during the control 

 period. The administration of thiamine to pigeons with preopisthotonus 

 caused return of the brain waves to normal. 



Horwitt and Kreisler,-- from their work on patients on diets with differ- 

 ent thiamine levels, tried to devise an index of carbohydrate metabolism, 

 correlating the levels of glucose, lactic acid and pyruvic acid in the blood 

 of the patient after a measured exercise and the carbohydrate metabolism 

 which is influenced by the thiamine intake. This carbohydrate index was 



'^ R. R. Williams, R. E. Waterman, J. C. Kcresztesy, and K. R. liuchman, /. Am. 



Chem. Sue. 57, 536 (1935). 

 »6 A. S. Schultz, L. Atkin, C. N. Frey, and R. R. Williams, J. Am. Chem.. Soc. 63, 



632 (1941). 

 '7 D. C. Smith and L. M. Proutt, Proc. Soc. Exptl. Biol. Med. 56, 1 (1944). 

 '« D. W. Woolley, J. Biol. Chem. 191, 43 (1951). 



'!» D. W. Woolley and A. G. C. White, J. Biol. Chem. 149, 285 (1943). 

 2" J. K. Kirk and M. Chieffi, J. Gerontol. 5, 236 (1950). 

 21 R. L. Swank and H. H. Jasper, Arch. Neurol. Psychiat. 47, 821 (1942). 

 " M. K. Horwitt and O. Kreisler, /. Nutrition 37, 411 (1949). 



