668 WOUND HEALING 8 



Russell (1956), who were unable to detect any change in the healing rate as 

 determined by decrease in area, and Savlov and Dunphy (1954b), who measured 

 wound tensile strength. Sandblom and Muren (1954) believed that the interval 

 between clipping the hair and wounding the skin is an important factor in such 

 studies. Depilated areas heal more slowly, probably due to vasoconstriction and 

 possibly to the release of inhibitory agents from the depilated site. The increased 

 tensile strength in resutured wounds (Botsford, 1941; Williams et al., 1951; 

 Savlov and Dunphy, 1954) may be due to local effects, e.g. increased vascularity 

 or concentration of fibroblasts, however, local excision of the primary wound 

 prior to resuturing fails to abolish the effect completely, and secondary wounds 

 when made at the primary site after the period of fibroplasia (15-40 days), 

 continue to heal more rapidly. Thus the factors affecting wound tensile strength 

 appear to be related to the local environment, but so far have not been completely 

 elucidated. 



Another approach to the wound hormone theory was pursued by Loofbourow 

 and his co-workers (1948), who demonstrated that yeast cells subjected to ultra- 

 violet radiation produced proliferation-promoting substances which are not 

 products of autolysis but are normal cellular constituents, released as a result of 

 increased permeability of the cell membrane or synthesized following injury. Their 

 chief effect is to stimulate cellular respiration, as demonstrated by Adelstein et al. 

 (1952), who found that oxygen consumption and carbon dioxide production of 

 normal cells were increased vipon exposure to the supernatant fluid of irradiated 

 yeast cells. The oxygen consumption is closely associated with the growth curve; 

 therefore, the effect is enhanced under aerobic conditions (Loofbourow et al., 1942). 

 Anaerobiosis alone will produce some growth increase, perhaps resulting from 

 greater permeability of the cell membrane. This type of reaction is not limited to 

 yeast and has been demonstrated in bacteria (Loofbourow and Morgan, 1940) 

 and cultures of fibroblasts containing chick embryo extracts (Loofbourow et al., 

 1939b). The nature of this growth-promoting substance is unknown, however, 

 in the supernatant, an increase in amino acids, vitamins of the B complex, nucleo- 

 tides, and nucleosides was demonstrated (Webb and Loofbourow, 1947; Loof- 

 bourow, 1947; Loofbourow et al., 1947). Most probably synthetic processes 

 within the damaged cells are responsible for this effect. The substance produced, 

 then diffuses through the cell wall, due to increased permeability. Although no 

 such mechanism has been demonstrated in mammalian wound healing, certain 

 evidence exists to indicate that it is possible. Since mechanical (Loofbourow et al., 

 1939a) or chemical (Loofbourow and Dwyer, 1939) damage to yeast cells will 

 produce the same result as irradiation, it is conceivable that the mechanical damage 

 incurred at a wound site might also result in the liberation of growth-stimulating 

 products. 



A relatively new and attractive concept with regard to the stimulus inducing 

 wound healing can be developed from the "coaptation" theory of Weiss (1947, 

 ig49a, b, 1950). Although the mechanics of cell reaction on a molecular level are 

 as yet unknown, his concept coincides with present facts and lends itself to 

 experimental verification. He has suggested that the affinity which exists between 

 certain cells (Bronsted, 1936; Holtfreter, 1939) may be due to specific stereochem- 



