XII. REQUIREMENTS AND FACTORS INFLUENCING THEM 293 



jinun without ill cfTects.-^ Proloii.u;e(l iKliniiiistration of 1 iii^. of pyiidoxine 

 to rats subsisting on diets restricted in either thiamine, riboflavin, or panto- 

 thenic acid failed to aggravate the manifestations of the deficiency state.-® 



Since pyridoxine deficiency in experimental animals causes such specific 

 and striking effects on the skin, on hematopoiesis, and on the central nervous 

 system, pyridoxine has been given in very large amounts to man for thera- 

 peutic trials in a large numlicr of conditions. No toxic effects have been 

 encountered with daily administration over periods of months of 50 to 2(X) 

 mg. of the vitamin by either the oral, intramuscular, intravenous, or intra- 

 thecal route."-^" 



Xo pharmacodynamic effects of large doses of pyridoxine are established 

 in man. Administration of large doses in attempts to prevent nausea and 

 vomiting in radiation sickness and during pregnancy rests, in the absence 

 of both an experimental basis and carefully controlled studies, on empiri- 

 cism. It may be remembered that ec^ually large doses of thiamine and of 

 niacinamide are also recommended for this purpose. Recent observations on 

 tryptophan metabolism in pregnant Avomen have shown that pyridoxine 

 prevents the excretion of abnormally large amounts of xanthurenic acid.^' 

 These findings may be analogous to the observations on tryptophan me- 

 tabolism in pyridoxine-deficient animals"-^- and, hence, imply an altera- 

 tion during pregnancy of metabolic functions in which pyridoxine is known 

 to play an essential role. Also, the low fasting blood level of urea of pregnant 

 women can be restored to normal A'alues by pyridoxine.*^ 



XII. Requirements and Factors Influencing Them 

 A. OF ANIMALS 



HENRY SHERMAN 



It is difficult to record the precise absolute requirement of animals for 

 vitamin Be , for there are many factors, external and internal, which in- 

 fluence this requirement. No single standard set of assay conditions or cri- 

 teria has received universal acceptance. Since A'itamin Be has at least a 



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" T. D. Spies, D. P. Hishtower, and L. H. Huhhard, J. Am. Med. Assoc. 115, 292 



(1940). 

 2' N. JollifTe, J. Am. Med. Assoc. 117, 1496 (1941). 



" N. JollifTe, L. A. Roscnhlum, and J. Sawhill, J. Invent. Dermatol. 5, 143 (1942). 

 '0 S. Stone, J. Nervous Mental Disea.'^e 100, 185 (1944). 

 " M. Wachstein and A. Gudaitis, ./. Lnb. Clin. Med. 40, 550 (1952). 

 3- S. Lepkovsky, E. Rolmz, and A. J. Ilaagen-Smit . /. Biol. Chem. 149, 195 (1943). 

 "W. J. McGanity, E. W. McTToiuy, H. B. Vnn \Vyci<, .ukI G. L. W.ilt, J. Biol. 



Chem. 178, 511 (1949). 



