Rats were tested on an allocentric-spatial working-memory task--delayed matching-to-place (DMTP) in a water maze--before and after either pyrithiamine-induced thiamine deficiency (PTD) or electrolytic lesions of the lateral internal medullary laminae (IML), an area damaged by PTD. DMTP trials consisted of paired swims, with the escape platform in a new location on each trial. PTD rats were impaired at retention delays of 300 s, but not at delays of 4 or 60 s. Rats with IML lesions performed normally at all delays. Both groups displayed normal retention of object-discrimination problems that they had learned at different intervals before treatment (5 weeks, 3 weeks, and 1 week). The results suggest that PTD causes delay-dependent deficits of allocentric spatial working memory and that damage outside the IML is probably responsible. Neither PTD-induced diencephalic damage nor restricted IML lesions appear to produce a global retrograde amnesia.
Trypsin-containing topical treatments can be used to speed wound healing, although the mechanism of action is unknown. To help form granulation tissue and heal wounds, monocytes leave the circulation, enter the wound tissue, and differentiate into fibroblast-like cells called fibrocytes. We find that 20 to 200 ng/ml trypsin (concentrations similar to those used in wound dressings) potentiates the differentiation of human monocytes to fibrocytes in cell culture. Adding trypsin inhibitors increases the amount of trypsin needed to potentiate fibrocyte differentiation, suggesting that the potentiating effect is dependent on trypsin proteolytic activity. Proteases with other site specificities such as pepsin, endoprotease GluC, and chymotrypsin do not potentiate fibrocyte differentiation. This potentiation requires the presence of albumin in the culture medium, and tryptic fragments of human or bovine albumin also potentiate fibrocyte differentiation. These results suggest that topical trypsin speeds wound healing by generating tryptic fragments of albumin, which in turn potentiate fibrocyte differentiation.
