Vll. \ri\Ml\ A Dl'.KIClliNCi 1\ WIMAl.S 133 



till- animal should he inciil iniicd. I'dl and .M('llaiil)\'" placed lihiac, lihulac, 

 radii, and ulnae ol' 17- to ■Ji-da.\-iild tetal mice into tissue culture media 

 eontainiiifi; 1000 (o 3000 I.l'. of i)ure \itamin A acetate per 100 ml. of 

 medium with the icsult that "the matrix of the ternunal cait ila,<:;e softened, 

 shrank, and linally almost or c()mi)letely disappeared, thouji;h the cartilage 

 cells appeared normal; iu the shaft the cartilage was rapidly replaced by 

 marrow tissue; th(> hone was resoihed, sometimes completely; the soft 

 tissue surrounding the explant grew as vigorously as in the controls culti- 

 vated iu normal medium." 



Barnicot'*- attached fragments of crystalline \-itamin A acetate by means 

 of fi))rin to small pieces of parietal bone removed from 10-day-old mice 

 and inserted the combination into the cerel)ral hemisphere of litter mates. 

 After the expiration of 14 days, the sit(> of the vitamin .V acetate showed 

 well-marked resorption and even jx'rforation of the imi)lanted bone. Osteo- 

 clasts, thought to l)e formed dc novo in the vicinity of the implant, were 

 regarded as the agents responsible for the resorption effect. Osteoblastic 

 acti\'ities persisted in regions remote from the vitamin A acetate. 



3. Teeth 



The bone supporting the teeth exhibits accelerated growth sequences 

 most prominent in the symphysis of the mandible. In guinea pig experi- 

 ments with large dosages, the changes at the symphysis result in painful 

 mobility. The growth sefiuences of the incisor teeth of rats and guinea pigs 

 do not involve remodeling processes. The formation of dentine and enamel, 

 though possibly accelerated, exhibits no apparent departure from the nor- 

 mal. Adequate studies of the effect of excess \itamin A on tooth growth 

 have not been made. 



4. Epithelial Tissues and Orgaxs 



I']pithelia which undergo keratinizing metaplasia in ^'itamin A delicienc}' 

 exiiibit no change in hyper\itaminosis A. 



The gross skin manifestations in humans — adults, children, and infants — 

 previously mentioned, have not been studied histologically, nor has their 

 specificity for hypervitaminosis A been proved. As they also occur in other 

 conditions, notably certain vitamin deficiency states, they may be the result 

 of nonspecific nutritional disturbances. Lesions of an inflammatory nature 

 in humans and experimental animals are found in those regions where 

 vitamin .\ comes into direct contact with the skin — mouth parts of the 

 human, and snout, paws, and other skin regions in animals. The gross and 

 histologic changes described in the literature have been produced in this 



^' H. B. Foil and E. Mellanl)y, Brit. Med. J. 11, 535 (1950). 

 « X. A. Biiriiicot, ./. Annt. 84, Part 4, 874 (1950). 



