286 PYRIDOXINE AND RELATED COMPOUNDS 



tion sickness with pyridoxine.'^'^"'^^ Various doses were used, from 25 to 200 

 mg. of pyridoxine. All reports recorded beneficial effects, in some instances 

 well controlled with placebos. ^^^ 



The greatest difficulty in accepting the beneficial effect of pyridoxine in 

 conditions such as nausea and vomiting of early pregnancy or following 

 general anesthesia as well as in radiation sickness is the lack of any direct 

 indication for a deficiency of vitamin Be in these conditions. Further, there 

 is no available proof for a direct pharmacological action of pyridoxine to 

 explain any clinical beneficial effect after administration of pyridoxine. 



As in any deficiency of a vitamin, it wouM be of great diagnostic value if 

 biochemical reactions could be found for the assessment of a spe ific met- 

 abolic disturbance connected with the vitamin in question, in this case 

 with vitamin Be . In tl:is connection the urea level in the blood may furnish 

 some indication for a specific metabolic abe-ration. It is known th it fasting 

 blood urea is significantly less in normal pregnant than in non -pregnant 

 subjects. The urea level is definitely lower in cases of hyperemesis gra\'i- 

 darum than in normal pregnancy, but it may be restored to typical normal 

 values after the administration of pyridoxine. ^^^ Although the lov level of 

 fasting blood urea is opposite to the condition found in pyrido dne-defi- 

 cient rats,^^^ the response to a test load of alanine is entirely simil ir. Blood 

 urea is increased to a maximum 6 hours after or.il administration of 30 

 mg. of DL-alanine, returning to original values within 12 hours in the non- 

 pregnant and normal pregnant woman. In women with hyperemesis gravi- 

 darum, blood urea levels rise but fail to derrease si-^nificantly bet ,veen the 

 sixth and the twelfth hours, thus exhibiting a flat cu.'ve. Supporti\'e therapy 

 alone for 72 hours does not alter the response to DL-alanine, but supportive 

 therapy supplemented with 120 mg. of pyi'idoxine produces normal preg- 

 nancy response to the test. 



More specific, at least for a relative vitamin Be deficiency, is the increased 

 urinary excretion of xanthurenic acid after a load test of tryptophan. ^^^ 

 Without this extra lo d of tryptophan, the excretion of xanthurenic acid, 



"' J. R. Maxfield, A. J. Mcllwain, and J. E. Robertson, Radiology 41, 383 (1943). 



1S8 L. M. Shorvon, Brit. J. Radiol. 19, 369 (1946). 



18" H. L. Van Haltern, Radiology 47, 377 (1946). 



"» A. Oppenheim and B. Lih, Radiology 47, 381 (1946). 



1" L. D. Scott and G. J. Tarleton, Radiology 47, 386 (1946). 



132 W. 1'. Murphy and M. C. Sossman, Trans. Assoc. Am. Physicians 59, 255 (1946). 



'"» J. J. Wells and W. C. Popp, Proc. Staff Meetings Mayo Clinic 22, 482 (1947). 



1"^ W. J. McCanity, 1-;. W. McHonry, ?I. H. Van Wyfk, and G. L. Watt, ./. Biol. 



Chen,.. 178, 511 (19-19). 

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