COMPOUND 48/80 ON RAT 



ous mast cells. Sufficient subcutaneous tissue for this purpose can be obtained 

 by scraping it off from under the surface of the excised skin. The mast cells 

 of the rat ear are in the dermis, but for assay, since so little dermis is available, 

 whole ears were employed. 



These various tissues were extracted as previously described and were 

 tested for histamine activity on the isolated guinea pig ileum preparation or 

 on the blood pressure of the atropinized cat. 



Microscopic examination. Fresh tissue spreads of subcutaneous connective 

 tissue, mesentery and omentum were prepared and fixed as previously described 

 and stained with 0-1 per cent aqueous toluidine blue. In studying the ear it 

 was found that once a narrow rim has been cut from its margin, the transparent 

 epithelium and attached connective tissue can be peeled off the outer surface 

 of the cartilage and glued to a slide, hairy side down, with a drop of B.P.S. 

 mountant, which holds it there firmly during fixation in alcohol. On defatting 

 with xylol, the preparation becomes detached and can be conveniently stained 

 and differentiated in watch glasses until it is finally mounted under a weighted 

 cover slip to keep it flat while the B.P.S. hardens. 



Results 

 ' Acute dosage ' experiment 



Within a few minutes of the intraperitoneal injection of an appropriate 

 dose of compound 48 80, the rat displays the characteristic signs of histamine 

 release — shock, erythema followed by cyanosis of the ears, and, in extreme 

 cases, visible oedema of the muzzle and extremities. The treated animals lie 

 in isolation, not huddled together as they normally do. There is an obvious 

 lowering of body temperature during the period of acute shock, but, given 

 abundant drinking water, the animals soon recover. 



Mast cells. In as short a time as three hours after the first intraperitoneal 

 injection of compound 48/80, a striking change occurs in the peritoneum. 

 Whereas in the controls injected with saline, the mast-cell picture is normal, 

 the first impression of the stained spread of mesentery and omentum from the 

 experimental rats is that the mast cells have completely disappeared. Even 

 under high power it is difficult to find an intact mast cell in the mesentery: 

 at most there remain a few irregular masses of darkly staining material near 

 the smaller blood vessels whose endothelial nuclei now stain with the basic 

 dye (Fig. 31). The mast cells scattered over the peritoneal windows have 

 vanished. In the omentum this disappearance of mast cells is somewhat 

 slower, but by one hour after the second injection the cells have under- 

 gone almost complete disruption. The milk spots are now crowded with 

 round or amoeboid cells, each of which contains a few peripheral masses of 



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