HYPERVITAMINOSIS A 607 



effect, with peeling. Escarras and Paillas^^^^ observed hyperkeratinization 

 and hyperplasia of the blood vessels as a result of a localized action of the 

 N'itamhi when applied to the skhi of the guinea pig. In hj^^ervitaminosis, 

 the most characteristic change is the great increase in lipids in the horny 

 layer of the squamous epithehum,"'-'"^ as well as in the number of young 

 non-keratinized cells. ^^^^ Keratinization was suppressed in rats,"'^ and 

 in chick embryo ectoderm explants/''^ bj^ excess vitamin A in the cultures, 

 b. Skeletal Lesions. The most characteristic disorders in hypervitami- 

 nosis A are bone fractures. Von Euler and WidelP'^" called attention to the 

 possibilit}^ of distm'bed bone growth in young rats treated with cod liver 

 oil, although they gave no definite data. The tjijical bone fractures were 

 described almost simultaneoush' b}^ Bomskov and Seemami,^"*' by Col- 

 lazo and Rodriguez, "^^ and by Davies and Moore."-'' Alultiple spon- 

 taneous fractures occur in the tibia and femur, producing a condition 

 resembling rickets."-^ Whereas the spontaneous fractures occur almost 

 exclusivel}^ in the case of 3'oung rats,^^-*''""'"-- hj'pochromic anemia and 

 hemorrhage are the more important abnormalities in older animals ex- 

 posed to h\q3ervitaminosis A. The most characteristic pathologic change, 

 according to Strauss,"-' is either increased acti\'it3^ of the osteoclasts, or de- 

 creased activity of the osteoblasts."-^ Longitudinal growth of the bone is 

 augmented more than lateral growth in h}TDer\'itaminosis A. Wolbach 

 and Besse}'''"'"' and later Wolbach alone "'^'^•"-•* postulated that, in hj^jer- 

 vitaminosis A, periosteal bone growth, i.e., the sequence of the growth 

 phases in the cartilage which precedes the endochondral bone formation 

 and the modeling of the bone, is increased, and the cartilage becomes cal- 



11" A. Escarras and J. Paillas, Compt. rend. soc. hiol., 129, 312-314 (1938). 



"12 X. Moll, O. Dalmer, P. v. Dobeneck, G. Domagk, and F. Laquer, Naunyn- 

 Schmiedeberg's Arch, exptl. Pathol. PharmakoL, 170, 176-207 (1933). 



1113 T. :Mo11, G. Domagk, and F. Laquer, Klin. Wochschr., 12, 465-467 (1933). 



111^ G. Domagk and P. v. Dobeneck, Virchow's Arch, pathol. Anat. u. Physiol., 290, 

 385-395 (1933). 



111= J. D. Sabella, H. A. Bern, and R. H. Kahn, Proc. Soc. Exptl. Biol. Med., 76, 499-503 

 (1951). 



1116 H. B. Fell and E. Mellanbv, J. Physiol, 119, 470-488 (1953). 



Ill" H. V. Euler and H. Widell, Z. physiol. Chem., lU, 132-136 (1925). 



1118 C. Bomskov and G. Seemann, Z. ges. exptl. Med., 89, 771-779 (1933). 



1119 J. A. Collazo and J. S. Rodriguez, Klin. Wochschr., 12, 1768-1771 (1933). 

 ii^) A. W. Davies and T. Moore, Biochem. J., 28, 288-295 (1934). 



1121 K. S. Strauss, Beitr. pathol. Anat. u. allgem. Pathol, 94, 345-352 (1934). 



1122 W. Papke, Z. ges. exptl Med., 101, 648-658 (1937). 



1123 J. T. Irving, J. Physiol, 108, 92-101 (1949). 



112^ S. B. Wolbach, Proc. Inst. Med. Chicago, 16, 118-145 (1946). 



