J. A. Wells

Potentiating Effect of Iproniazid on the Pharmacological Action of Sympathomimetic Amines.

Summary Iproniazid, in a dose of 0.18 millimoles/kg potentiates the action of phenylethylamine and tyramine upon the nictitating membrane of cats. The action of epinephrine is not changed significantly. Isoniazid does not have this effect when given in equivalent doses.

Adrenergic blockade by iproniazid

1-Isonicotinyl-2-isopropylhydrazin (Iproniazid) blokkiert reversibel den Angriffsort des Adrenalins im Furchgottschen Präparat der Kaninchenaorta. Die Wirkung wird der strukturchemischen Ähnlichkeit zwischen Adrenalin und Iproniazid zugeschrieben.

Modification of Anaphylaxis by Benadryl.

Summary The intravenous injection of Benadryl (10 mg per kilo) into horse serum sensitized dogs, prior to the reinjection of horse serum, reduces the severity of anaphylactic shock in these animals, there being no deaths in 22 animals as against 9 deaths in 26 controls. As Benadryl has a similar modifying effect upon the shock induced by the injection of histamine, the results of these experiments are consistent with the theory that histamine plays a significant role in anaphylaxis in dogs. Unfortunately, Benadryl merely reduces, but does not obliterate, the vasodepressor effects of histamine and thus the present experiments with Benadryl do not permit conclusions as to whether histamine is or is not the sole vasodepressor factor in anaphylaxis in the dog.

Significance of histamine in trypsin shock as determined by benadryl.

Summary It was found that benadryl, a potent antagonist to either injected or liberated histamine, does not modify the lethal action of trypsin in the guinea pig or the dog. It is thus apparent that the histamine hypothesis, relative to the toxicity of trypsin, requires reconsideration.

Comparison of Leukocyte Response to ACTH and Bacterial Pyrogen.

Summary The leukocyte response to bacterial pyrogen is superficially similar to that produced by ACTH. However, removal of the adrenals substantially modifies the response to ACTH in the dog, but is without effect on pyrogen induced leukocyte responses. It is concluded that pyrogen produces its characteristic changes in the W.B.C. count by mechanisms other than pituitary-adrenal discharge.

Mechanism of pyrogen induced fever.

Summary Typical pyrogen induced fever occurs under conditions in which increased heat production due to activity of skeletal muscles is not possible. Under these conditions the mechanism of the pyrogenic reaction is one of sudden and marked reduction of heat loss. The slight increase in heat production under these conditions is correlated with the rise in temperature and is assumed to be a consequence rather than a cause of the fever.

Observations on the Antagonism Between Heparin and Trypsin.

Summary Heparin does not appear to be specific antitryptic substance since it prevents neither the fall in blood pressure produced by trypsin in the dog nor the proteolytic activity of trypsin on a hemoglobin substrate. However, heparin does protect guinea pigs against the lethal effects of intravenously injected trypsin. The observation that fastusol, like heparin, protects rats against the lethal effects of trypsin is compatible with the notion that such a protective action on the part of heparin is related to its anticoagulant properties.

Influence of Adrenergic Blocking Drug [N-Ethyl-N-(2-bromoethyl)-l-naphthylenemethylamine · HBr] On Pyrogenic Reaction.

Summary A potent adrenergic blocking drug, N-Ethyl-N- (2-bromoethy1)-1-naphthyl-enemethylamine · HBr, has been shown to reduce and alter the febrile response of normal and curarized dogs to the intravenous injection of a purified pyrogenic material obtained from pseudomonas aeruginosa. This evidence is interpreted as supporting the hypothesis that the pyrogenic reaction is due, at least in part, to a reduction in heat loss caused by adrenergic nerve mediated vasoconstriction in the skin.

Attempts to Prevent Ergot Gangrene with Heparin and Dicumarol. Vascular Effects of Ergot by Fluorescein Technic

Summary Twenty-four hours after the administration of a single dose of ergotamine tartrate, approximately 50% of rats showed, by means of the fluorescein test, a seriously impaired circulation to the tail, due to marked constriction of the major arteries of the tail. Forty to 50% of rats receiving a single dose of 12.5-37.5 mg/kg of ergotamine tartrate may be expected to develop gangrene of the tail and to begin to do so within one week of the injection of ergotamine. Anticoagulants, such as heparin and dicumarol, do not alter the incidence of ergotamine induced gangrene. It is concluded that the thrombosis, observed to be associated with this process by others, is incidental rather than contributory to the vascular occlusion.

Gastric secretion in enterectomized dogs

1. A continuous hypersecretion of highly acid gastric juice was observed in dogs following either removal of the small intestine, or exclusion of gastric, pancreatic, and biliary secretions from the small intestine. 2. This hypersecretion appears to be related mainly to the stimulatory effects of the surgical intervention and post-operative care, rather than to a possible release from the inhibitory effects of enterogastrone.