II THE STIMULUS FOR WOUND HEALING 667 



cultures was stimulated by extracts of inflammatory tissue. A similar concentrated 

 diffusate, when injected repeatedly into the nipple of non-pregnant rabbits, 

 induced some growth response (Menkin, 1953, 1955, 1956). The growth- 

 promoting action of protein degradation products in vitro appears well established 

 (Carrel and Baker, 1926; Willmer and Kendal, 1932; Davidson and Waymouth, 

 1944a, b). Embryo extracts which contain a large quantity of these substances also 

 stimulate tissue culture growth, and Fisher (1930) has shown that when cells in 

 culture are wounded, the remaining ones grow faster — an observation confirmed 

 by Svmtzowa (1944). 



A number of references in the literature indicate that embryo juice has a 

 favorable action on wound healing (Bergami, 1925; Roulet, 1926; Wallich, 1926; 

 Carnot and Terris, 1926; Carrel and Baker, 1926; Kiaer, 1927; Bugliari, 1927; 

 Schloss, 1928; Nakamura, 1930; Nielsen, 1939; Waugh, 1940; Egorov, 1943). 

 Many believe the active growth principle of embryo extract to be a pentose- 

 nucleoprotein (Fisher, 1939, 1940, 1942; Davidson and Waymouth, 1944a, b) 

 although others were unable to confirm this (Dvorak and Byram, 1930; Auerbach 

 and Doljanski, 1944; Doljanski and Auerbach, 1944). Fisher (1939, 1940) 

 claimed to have isolated an active principle from embryos, "embryonin", but this 

 has not been confirmed by other investigators (Young et al., 1941 ; Botsford, 1941 ; 

 Dann et al., 1941). At present there is no evidence that such embryonic extracts 

 have any action other, than as nutrient materials (Davidson, 1943, 1945)- The 

 healing rate of a non-infected wound in a well-nourished individual is not in- 

 creased by such products, and it is questionable whether they affect the healing- 

 rate under any circumstances. A substance with a specific catalytic effect on 

 healing which would conform to the definition of a "wound hormone", has still to 

 be demonstrated. 



There are some facts indicating that the stimulus for wound healing may be 

 of a humoral nature. Auerbach et al. (Auerbach and Doljanski, 1944; Doljanski 

 and Auerbach, 1944), treating rat wounds with either adult or embryonic tissue 

 extracts, found that control wounds on treated animals healed faster than control 

 wounds on untreated animals. This could only be explained on the basis of a 

 humoral mechanism. Furthermore, rats receiving intraperitoneal injections of 

 saline-extracted adult chicken hearts, healed approximately 20% more rapidly 

 than controls (Auerbach and Doljanski, 1945). Lorin-Epstein (1927) reported 

 the presence of substances in the serum of wounded animals which accelerated 

 healing, and Akamatsu (1922) demonstrated that plasma from such animals 

 produced better growth in tissue culture than plasma from intact animals. 

 Verification of a humoral substance which would directly stimulate healing is 

 lacking, and clinical studies have not substantiated this concept. 



The relationship between the healing rate of primary and secondary wounds 

 has resulted in contradictory findings. If a secondary incision heals more rapidly 

 than a distantly placed primary incision, a humoral mechanism can be inferred, 

 as suggested by Lorin-Epstein (1927), Young, Fisher, and Young (1941), and 

 Sandblom (1949), however other investigators obtained negative results (Carnot 

 and Terris, 1926; Taffel et al., 1950; Williams et al., 1951; Engley et al., 1955). 

 The bulk of evidence favors the carefully controlled studies of Billingham and 



I.iteraluTC p. 705 



