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Date of Award

1971

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Graduate Studies

First Advisor

Marvin H. Malone

First Committee Member

Carl C. Riedesel

Second Committee Member

John K. Brown

Third Committee Member

Donald M. Pace

Fourth Committee Member

Herschel G. Frye

Abstract

This study was conducted in an attempt to define the anti inflammatory efficacy of cryogenine, the major alkaloid of Heimia salicifolia Link and Otto. The anti inflammatory effects produced by cryogenine, phenylbutazone, indomethacin, mefenamic acid, paramethasone, hydrocortisone and 6-mercaptopurine were compared considering the sequential changes in various motameters during the course of adjuvant-induced polyarthritis in rats. Polyarthritis was induced by the subplantar injection of a suspension of heat-killed Mycobacterium butyricus in mineral oil into the right hind paw of Sprague-Dawley rats. The manifestations of the diseases were monitored in terms of hind paw swelling, subjective appearance of secondary lesions, impairment of body growth, and various hematological/serological changes. Effects produced by cryogenine in ganglia and acute cardiovascular interactions with various mediators of inflammation and vasoactive agents were also investigated in the rat. Although cryogenine is structurally unrelated to any known class of anti inflammatory, antipyretic or analgesic compounds, it has been shown to be effective in several experimental inflammatory conditions which respond to the anti inflammatory drugs presently in clinical use. Its nonspecificity of action against neuro- and tissue hormones suggest that its anti inflammatory activity is not related primarily to inhibition of acute phase reactants or to peripheral neurotrophic effects. Involvement of the pituitary-adrenal axis in the therapeutic efficacy of cryogenine seems improbable.

Pages

145

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