EFFECT OF DEFICIENCY IN ANIMALS 



Rats 



As already noted (page 462) folic acid, in conjunction with biotin, 

 cured the achromotrichia caused by administration of sulphonamides 

 to rats, 23. 24 whilst folic acid alone cured the leucopenia and granulo- 

 cytopenia observed in such rats ^s and corrected the vitamin K-de- 

 ficiency produced by sulphasuxidine.^^ These early observations were 

 confirmed by subsequent investigations in which various forms of 

 folic acid were used. Thus Higgins,^' using the sulphones, promin 

 and promizole, to produce an experimental hypochromic anaemia in 

 young rats maintained on a purified high-carbohydrate diet, showed 

 that vitamin Be given at the rate of 80 fjig. per day had a pronounced 

 curative effect. Similarly, the L. casei factor cured a leucopenia and 

 granulocytopenia produced in rats by administration of succinyl 

 sulphathiazole, whilst the marrow responded with " spectacular 

 myeloid proliferation ".^^ 



Again, rats that had ceased to grow and in which characteristic 

 deficiency symptoms had developed following administration of 

 sulphaguanidine responded to liver extract or to a folic acid concen- 

 trate plus biotin ^^ with a reduced mortality rate of 14 % and dis- 

 appearance of liver and spleen lesions ; at the same time the bone- 

 marrow became hyperplastic. 



That the action of sulphonamides on haemopoiesis is probably 

 mediated through the agency of intestinal bacteria appears to be a 

 legitimate deduction from the work of B. L. O'Dell and A. G. Hogan,^^ 

 who showed that reducing the level of pyridoxine or feeding sulpha- 

 guanidine increased the incidence of anaemia in chicks ; they suggested 

 that in both instances growth of the intestinal bacteria that normally 

 synthesised vitamin Be was suppressed. The absence of other factors 

 essential for the growth of the intestinal bacteria might equally well 

 result in suppression of the intestinal flora, leading to a deficiency of 

 vitamin Be and so to an increase in the incidence of anaemia. 



Further evidence on the natiure of intestinal synthesis was advanced 

 by A. K. Miller, ^^ who confirmed the results obtained by previous 

 workers that folic acid and biotin together corrected the deficiency 

 symptoms caused by feeding 0-5 to 2-0 % of succinyl- or phthalyl- 

 sulphathiazole with the diet. He also noted a marked decrease in 

 the coliform coimt of the faeces, .but no significant change in the 

 total aerobes, total anaerobes or anaerobic spores. Neither sulphon- 

 amide-resistant nor sulphonamide-sensitive strains of E. coli were 

 able to synthesise as much folic acid when grown in presence of a 

 sulphonamide as when grown in its absence. He therefore concluded 

 that E. coli or, at all events, coliform organisms, were responsible for 

 the synthesis of folic acid in the gut (see page 505). 



Still further confirmation of the part played by the intestinal 



487 



