yOO WOUND HEALING 8 



tissues (Dziewiatkowski, 1949). Autoradiographs of skin following such a dose 

 reveal a low uptake in the cornified layer and a somewhat greater quantity evenly 

 distributed throughout the dermal papilla and outer root sheaths of hair follicles 

 and small vessels (Bostrom et al., 1953; Montagna and Hill, 1957). Bostrom and 

 Gardell (1953) showed that the large majority of ^^S is attached to the chondroitin 

 sulfui^ic acid moiety which was first discovered by Meyer and ChafTee (1941) in 

 pigs and later in human skin by Pearce and Watson (1949). Dermal mast cells 

 are foci of high activity, related most probably to ester sulfate groups of heparin 

 (Jorpes et al., 1953; Asboe-Hansen, 1953). The uptake is low in most other sulfur- 

 containing compounds of skin. (See for review Bostrom, 1953; Bostrom and Jorpes, 

 1954; Bostrom, 1957.) 



Layton (1950a, 1951) was the first to demonstrate the increased uptake of 

 -'^S in granulation tissue both in vitro and in vivo. This appears to be related to 

 collagen formation since it is minimal around the immature fibroblasts of early 

 wounds and later decreases when collagen deposition is completed (Upton et al., 

 1955). Glucksmann et al., (1956) by means of autoradiographs have observed that 

 •^^S sulfate is incorporated into the fibroblasts prior to fiber formation. In older 

 wounds when collagen formation is active, the main concentration of ^^S is in the 

 fiber bundles, which supports the conclusion of those who claim that fibroblasts are 

 the source of mucopolysaccharides (Gersh and Gatchpole, 1947; Goon and Upton, 

 1952). Kodicek and Loewi (1955) noted that the ^^S uptake is greatest during the 

 stage when polysaccharides are most concentrated in the wound. They suggested 

 that sulfation of the mucopolysaccharide component may be a necessary prerequi- 

 site to collagen formation. In Vitamin G deficient aminals the uptake is markedly 

 decreased though normal amounts of polysaccharide are present as shown by 

 hexosamine determinations (Upton et al., 1955; Upton and Odell, 1956; Kodicek 

 and Loewi, 1955). The difTerent staining reaction present in the scorbutic animal 

 further supports the concept that the polysaccharides are abnormal (Penny and 

 Balfour, 1949; Gampani and Reggianini 1950; Persson, 1953; Bunting and White^ 

 1950). Kodicek and Loewi (1955) believe that either the polysaccharide cannot 

 be sulfated because of this abnormality or else the absence of Vitamin G impairs 

 some enzyme system necessary for this sulfation. 



The uptake of sulfate ion, which plays a role in formation of the grovnid sub- 

 stance, must be distinguished from the uptake of sulfur in amino acid. Sulfate 

 does not enter in large quantities into the sulfur-containing amino acids (Dzie- 

 wiatkowski, 1954; Tarver and Schmitt, 1939). The largest part of the non-sulfate 

 sulfur appears to be bound to the protein of granulation tissue. 



Harvey and Howes in 1930 showed that the level of protein intake markedly 

 affects the healing rate of wounds, and their findings have since been verified many 

 times (Thompson et al., 1938; Localio et al., 1943; Morris^/ a/., 1945; Munroe and 

 Ghalmers, 1945; Ghalkley ^/a/., ig^6; Abbot etal., 1946; Gharney ^/o/., 1947; Varco, 

 1 947 ; Williamson f / a/. , 1 95 1 a ; Sandblom et dj/. , 1 953 ; Udupa et al. , 1 956) . Williamson 

 and his co-workers (Williamson et al., 1951b) established that it is the protein-sulfur 

 rather than protein nitrogen component which is essential for this function. Further 

 evidence of the importance of sulfur is its relative retention in granulation tissue, and 

 this directly correlates with the healing index despite a negative nitrogen balance 



