516 THE BIOCHEMISTRY OF B VITAMINS 



p-aminobenzoic acid alone at low concentrations exerts no effect on 

 rhythm or amplitude, sulfanilamide at low concentrations increases 

 amplitude, but does not accelerate rhythm, and at high concentrations 

 stops the frog heart. 311 p-Aminobenzoic acid may under certain conditions 

 inhibit the contractions of isolated frog heart. 312 The incidence of con- 

 vulsions after intramuscular injection of procaine in guinea pigs is 

 Teduced by previous administration of either diethylaminoethanol or 

 p-aminobenzoic acid, or to a greater extent by both compounds. 313 Other 

 compounds structurally related to p-aminobenzoic acid and diethylamino- 

 ethanol exert a similar effect. 313 No inhibition of the peripheral local 

 anesthetic action of procaine occurs with these compounds. 313 The effects 

 are presumably unrelated to the catalytic roles of p-aminobenzoic acid. 



The effect on intestinal contractions of procaine in physiologically 

 active concentrations is suppressed by sulfanilamide in concentrations 

 eight times that of procaine. 314 



Either p-aminobenzoic acid or diethylaminoethanol prevents competi- 

 tively the typical convulsive action of procaine in guinea pigs. 315 



The formation of a yellow pigment in cultures of Mycobacterium 

 tuberculosis in the presence of p-aminobenzoic acid or procaine is inhib- 

 ited by sulfanilamide. 316 - 317 The oxidation of p-aminobenzoic acid to a 

 red-colored substance by peroxidase from horseradish is also prevented 

 by sulfanilamide. 317 



Sulfanilamide, sulfathiazole or sulfapyridine inhibits the peroxidase 

 reaction, but not phenol oxidase with p-aminobenzoic acid as a sub- 

 strate. 317 



Carbonic anhydrase is inhibited by sulfanilamide, 318 but the inhibition 

 is only partially counteracted by p-aminobenzoic acid. 319 



An interesting adsorption effect has been reported in which sulfanila- 

 mide (0.1 per cent) decreases by 44 per cent the amount of methylene 

 blue adsorbed by charcoal. p-Aminobenzoic acid (0.028 per cent) com- 

 pletely prevented the effect of sulfanilamide on the adsorption. 320 The 

 possibility that sulfonamides act bacteriostatically by reducing cellular 

 and colloidal adsorption was suggested. 320 



Resistance to Sulfonamides 



Natural Resistance. Many organisms, either isolated from patients or 

 tested at random, have been found to possess a "natural" resistance to 

 the sulfonamides. 321-333 For example, two strains of Staphylococcus 

 aureus isolated from patients with severe infections differed in their 

 susceptibility to sodium sulfathiazole before treatment was adminis- 

 tered; 321 and from 168 patients with pneumonia, meningitis or endo- 

 carditis, moderately resistant organisms were isolated from six cases. 322 



