Y METABOLIC CHANGES 619 



ministered at an early stage it inhibits regeneration. Reciprocally the regener- 

 ated mucopolysaccharides may inhibit the earlier stages of cell-proliferation 

 (Balazs and Holmgren, 1950). They also inhibit the sprouting of regenerating 

 nerve-fibres (Hoffmann, 1952), probably again by preventing lysis of the tough 

 connective tissues of the innervated organs. Certain pyrogenic polysaccharides 

 counteract this, possibly competitively, and induce the development of a delicate, 

 easily penetrated stroma of connective tissue (Hoffmann, 1954; Bammer and 

 Martini, 1953)- For the same reason mucopolysaccharides prevent the migration 

 of leucocytes (Meier et al., 1955), and of blastema-forming cells (Lehmann,i954). 

 The action of the pyrogenic polysaccharides recalls the anticoagulant action of the 

 polysaccharide heparin, which in fact probably plays some part in the early stages 

 of the GAS (Asboe-Hanson, 1952; Bloom 1952). 



(/) Fat-metabolism 



There is little knowledge of the metabolism of lipids during the regeneration 

 of structures other than the liver and peripheral nerves of mammals ; both are 

 peculiar, the liver because of its function in the intermediate metabolism of fats 

 and the nerve-fibre because of its thick lipoid myelin sheath. After partial hepat- 

 ectomy there is a rapid increase in liver-fat (Ludewig et al., 1939; Harkness, 1952; 

 Johnson and Albert, 1952; Yarbro and Anderson, 1954; Tsuboi et al. 1954), 

 from 3.3% of the wet-weight to 7.6% at 10 h, when all other constituents, except 

 water, are decreasing in amount. This response is not peculiar to liver-regenera- 

 tion (Frazer, 1954; Gaunt, 1954). It is probably the counterpart (Selye, 1948; 

 Cuthbertson, 1954) of protein- and carbohydrate-flow. The fat comes mainly 

 from the depots (Yarbro and Anderson, 1954). It is not required mainly as a 

 source of energy. As a fuel, fat is certainly not more important than carbohydrate. 

 Weisz (1949) found a depletion of glycogen in regenerating Protozoa but not of 

 fat and this is probably true of cells growing m vitro (Willmer, 1953). Fat is said 

 to depress healing in mammals (Whipple, 1940) though Rogers et al. (1950) found 

 that as much as 30% of fat in the diet was beneficial. 



There is considerable evidence that lipids do play a relevant part in regener- 

 ation. Most lipid fractions show two cycles of abundance (Table 8), in regener- 

 ating liver, one of which may be part of the non-specific GAS and the other spe- 

 cific to regeneration. If hepatic trauma is induced chemically, by carbon tetra- 

 chloride (Tsuboi et al., 1951), the initial increase in lipids is delayed by one or 

 two days, presumably associated with the greater demolition necessary than after 

 surgery. The second maximum of fat-concentration, around the eighth day after 

 hepatectomy, is associated with increased lipolytic activity (Bertolani et al ., 1954; 

 Tsuboi et al., 1954). Cavanagh and Webster (1955) found two maxima in lipolytic 

 (ali-esterase) activity in regenerating nerve so that the two cycles may be common 

 (p. 611) among metabolic processes during regeneration. 



The turnover of phospholipid in regenerating liver is maximal around the 

 third day (Johnson and Albert, 1952) at the time of maximal cell-proliferation. 

 Since the concentration of P-lipid is by then decreasing from its initial peak, it is 

 probably being used for cell-growth or -proliferation. There is much evidence 

 (Davidson and Leslie, 1950; Hammarsten, 1951; Singal et al., 1952) that phos- 



Lilerature p. 64^ 



