THE MAST CELLS 



1, 4, 8, 15 and 32. 'Subacute dosage' expt., at days 3, 5, 11, 15, 18 and 32. 

 'Chronic dosage' expt., at days 5, 15, 24 and 32. 



On each occasion one animal from each group, chosen at random, was 

 used for histological purposes, pooled tissues from the remainder being assayed 

 for histamine. In the 'chronic dosage' experiment, four further groups of 

 rats were injected intraperitoneally with a volume of saline equal to that 

 used as a solvent for compound 48 80 and killed at the times stated. Again 

 histamine values and the histological picture in each of these control groups 

 were determined. 



Histamine-liberator. Compound 48 80, kindly supplied by Messrs. 

 Burroughs Wellcome and Co., was made up fresh in normal saline and injected 

 intraperitoneally low down on the abdominal wall, the dosage, measured in 

 micrograms ((J-g.), being as follows: 



'Acute dosage' expt. 100 (morning), 200 (afternoon). 



'Subacute dosage' expt. Injection twice daily, starting at 100 per dose 



and increasing the dose by 100 each day to reach a dose of 500 on the fifth 



day. 



'Chronic dosage' expt. Dosage as for 'subacute dosage' experiment for 



the first five days, thereafter single daily injections of 500 with increments 



of 100 every other day to reach 1000 per day, and continuing at this level 



of dosage once daily up to the thirty-first day of the experiment. 



Intra-arterial Experiment. Injections in this group were given into the 

 artery of the ear. From previous work in which the vascular system of the rat 

 was injected with coloured substances (Riley, 1953a) it was known that the 

 main blood supply of the ear comes from the first branch of the external 

 carotid artery. Accordingly this vessel was exposed in ten rats under ether 

 anaesthesia by cutting the oblique muscle covering the carotid on the left side 

 at its tendinous insertion under the mandible and retracting it posteriorly, 

 at the same time turning the submaxillary salivary gland forwards to expose 

 the entire cervical vessels. A hypodermic needle bent to a convenient shape 

 was then inserted into the common carotid to lie in the origin of the external 

 carotid. After the external carotid had been occluded beyond the branch to 

 the ear by light pressure with a probe, a single dose of 200 fzg. of compound 

 48/80 was injected slowly. Of ten rats so treated, eight subsequently developed 

 erythema or cyanosis of the injected ear and were killed twenty-four hours later. 

 The histamine content of pooled left ears from six rats was compared with the 

 histamine content of pooled right ears (control) and then correlated with the 

 histological findings in the ears of the remaining two animals. 



Histamine assay. For the estimation of histamine content mesentery, 

 omentum and subcutaneous tissue were chosen because they all contain numer- 



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