XI. PHARMACOLOGY 393 



burns ()!• sur<i;ic:il procedures whore i)ro(ein losses iiidicale cellular decom- 

 position.-'^ 



The riboflavin content of the blood is relatively constant'-' -•' (ui)pro.\i- 

 mately 40 y per 100 ml.) when measured by microbiological techniques. 

 However, since the ingestion of riboflavin can cause a 30% increase in the 

 flavin adenine dinucleotide content of the red blood cell,^'' it is likely that 

 the use of improved methods-* will show a correlation between dietary and 

 erythrocj'te content. 



Although there is no appreciable storage capacity of riboflavin in animal 

 tissues, it is apparent that the amount can vary, since the organs of animals 

 will lose as much as two-thirds of their original content when the animals 

 are fed riboflavin-deficient diets.-®"-^ A combined protein and riboflavin 

 deficienc}^ is especially effective in decreasing the riboflavin content of the 

 tissues of the growing rat.-^ Diets on which signs of clinical ariboflavinosis 

 are observed are usually low in protein. 



The concept of a rational pharmacology based upon antivitamins, which 

 was pioneered by Woolley,^" has greatly stimulated the search for ribo- 

 flavin antimetabolites. Wright and Sabine'^' have shown that flavin adenine 

 dinucleotide lowered the atabrin inhibition of tissue respiration and of d- 

 amino acid oxidase. This, and a similar observation by Haas*- with respect 

 to cytochrome reductase, led Hellerman, et al.^^ to quantitize the metabolic 

 antagonisms of antimalarials like atabrin and quinine.'^^' ^^ The phenazine 

 analog of riboflavin,^^ as well as isoriboflavin,^^ when fed to mice and rats 

 produced ariboflavinosis. 



-" H. Pollack and S. L. Halpern, Tfierapeutic Nutrition, National Research Coun- 

 cil, 1951. 



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"M. K. Horwitt, E. Liebert, O. Kreisler, and P. Wittman, Butt. Natl. Research 

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