Abstract
When various types of inflammatory exudates obtained from dogs or rabbits are introduced into the normal skin of either of these animals an immediate vasodilatation and increased capillary permeability follow. This is demonstrated by the diffuse accumulation of a dye (trypan blue) from the circulating blood into areas treated in this way. 1 , 2 , 3 This finding suggests that an active substance increasing capillary permeability is present in exudates. The effective agent may be recovered by treating the exudates with saturated ammonium sulphate or 20% sodium sulphate. It is thermostable and is active at pH 7.4 to 6.5. Dialysis of the ammonium sulphate treated exudate yields a water soluble crystalline material in the evaporated dialysate which is fully potent, whereas the dialyzed material remaining in the cellophane bag is inactive. Direct dialysis of the untreated cell-free exudate likewise yields some of the active material in the evaporated dialysate. By this latter procedure, however, a small part of the active material remains in the cellophane bag apparently in a non-diffusible form. Since the active substance does not possess the properties of histamine, a definite objection is raised to the hypothesis of Sir Thomas Lewis which involves the action of histamine or an “H-like” substance. 4 Histamine in the rabbit skin in varying concentrations dissolved in either water, saline, or serum causes central blanching and occasionally a peripheral accumulation of the dye from the blood stream in a “flare-like” formation. The active material found in exudates induces diffuse accumulation of dye throughout the treated skin area. Histamine contracts the guinea pig intestine. The active material from exudates, on the other hand, relaxes the isolated strip of intestine. These opposed effects would rule out the possibility that the active material in exudates is histamine or its closely related H-substance.
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