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Identify abortifacient toxins in pine needles and broom snakeweed and determine metabolism and clearance times. Describe the pathophysiologic, endocrine, immunologic, and morphologic changes associated with the abortions, and define mechanisms. Describe their physiologic activity, toxicokinetics, and mechanisms of action of teratogenic plants. Determine plant, animal, environmental and management factors influencing consumption of these plants and develop management strategies that will reduce losses.
Unknown alkaloids will be isolated and characterized from larkspur species using large scale extraction followed by acid/base extraction to yield a crude alkaloid fraction. HPLC will be used to purify alkaloids for toxicity testing. Development of new analytical methods for larkspur alkaloids will continue. Immunogenic alkaloid-protein conjugates will be synthesized and immunized into animals. The resulting antibodies will be characterized, and if suitable, will be developed into ELISA detection systems. Immunogenic conjugates will be tested in animals as vaccines to determine if immunization alters larkspur toxicity. Rates of toxic metabolism and clearance will be determined using extracts and purified alkaloids. Diagnostic procedures will be enhanced. Treatment of intoxicated animals using cholinergic drugs will continue. Field and pen studies will evaluate plant, animal, and environmental factors influencing larkspur consumption and toxicity. Management options such as sheep grazing, aversive conditioning.