p-AMINOBENZOIC ACID 515 



Increased excretion of urobilins has been observed in rats treated with 

 sulfonamides. 293 



The addition of succinylsulfathiazole to a highly purified diet deficient 

 in inositol inhibited the growth of rats and caused alopecia, which was 

 cured with inositol. 294 



Phthalylsulfathiazole administered to the pig on a diet deficient in 

 inositol and biotin caused a syndrome which could be prevented by the 

 addition of biotin, but was also largely alleviated by inositol. 295 It has 

 been suggested that the sulfa drugs inhibit intestinal microorganisms 

 which synthesize inositol and thereby cause a deficiency. 296-298 Sulfa- 

 guanidine in combination with inositol reduces the fertility of female 

 albino rats, whereas either compound alone has no effect. 299 



Succinylsulfathiazole fed to pigs on a purified diet produces an 

 anemia 300, 301 which responds to treatment with either folic acid, or less 

 effectively with purified liver extracts. Earlier failures 302, 303 to accom- 

 plish this result have been explained on the basis of the relatively long 

 period of treatment necessary to obtain this effect. Both folic acid and 

 biotin are necessary to prevent the effects of the sulfonamide on the pig; 

 however, folic acid administered without biotin accelerates the appearance 

 of biotin deficiency symptoms. 301 Thus, the interrelationships of these 

 factors in the pig appear to parallel those in the rat. 



The nutritional requirements of rabbits 304 and chicks 305, 306 are re- 

 ported to be affected by sulfaguanidine. On the other hand, succinylsulfa- 

 thiazole does not appear to increase the nutritional requirements of 

 chicks. 307 



Succinylsulfathiazole added to purified diets fed to mice retards the 

 growth of the animals. 308 Supplements of folic acid and biotin together 

 do not counteract this effect ; but these factors, together with liver extract, 

 prevent the toxic action of the sulfonamide on growth of the animals. 

 Concentrates of vitamin B i2 almost completely replace the liver extract. 308 



Sulfanilamide, 125 mg injected daily, prolonged nerve chronaxia and 

 shortened muscle chronaxia in rats. 308a These effects, which are similar to 

 those in chronic alkalosis, are prevented by daily oral administration of 

 ethyl p-aminobenzoate (50 y), nicotinic acid (400 y), riboflavin (20 y), 

 or ascorbic acid (5 mg) . No effects were observed with thiamine, adenine, 

 pantothenic acid or pyridoxine. 



3-Hydroxysulfanilamide has been identified in human urine as a 

 metabolic product of sulfanilamide. 309 



It has been reported that the toxicity for rats of bis(4-a-aminovaleryl- 

 phenyl)sulfone or related sulfones is diminished by administration of 

 either p-aminobenzoic acid or ascorbic acid. 310 



Miscellaneous Effects. p-Aminobenzoic acid is reported to counteract 

 the depressant effect of sulfanilamide on isolated frog hearts. 311 While 



