Abstract.New drugs for causal prophylaxis of malaria are needed. A proguan il/sulfamethoxazole combination was investigated using a rhesus monkey model (Macaca mulaiia infected with Plasmodium cynomolgi) to determine whether causal prophylaxis could be achieved. When a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day) was used, infection of all animals (6 of 6) was observed, with an extended prepatent period (median 40 days). Two control animals became infected on days 9 and 23 following sporozoite inoculation. Plasma concentrations indicated that proguanil and sulfamethoxazole were adequately absorbed and metabolized to cycloguanil and N4-acetylsulfamethoxazole, respectively. Analysis of liver biopsy specimens demon strated that the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole does not eliminate exoerythro cytic-stage parasites in the rhesus monkeyâ€"P. cynomolgi model.
The area postrema (AP) is being widely studied to delineate its role in such varied functions as blood pressure regulation, conditioned taste aversion, water and energy balance, and radiation-induced emesis. This paper describes the preoperative preparation, surgical procedure, and postoperative care of cats kept long-term in which the AP was lesioned by electrocautery. A dorsal midline approach under gas anesthesia allowed access to selectively lesion the AP. Cats fully regained consciousness the same day and many became homeostatic within 24-48 h. Results of experiments using this model demonstrate the usefulness and effectiveness of the technique for model preparation.
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