Prolongation of renal allograft survival in a large animal model by oral rapamycin monotherapy.

We assessed the efficacy of 5 dose levels of oral rapamycin for prolonging renal allograft survival in pigs. Untreated and triple therapy groups (cyclosporine, azathioprine, and prednisone) served as controls. Immunosuppression was administered for 28 days posttransplant and then stopped. Rapamycin whole-blood concentrations were followed weekly. Chemistry, hematology, and lipid values were monitored post-transplant. For rapamycin-treated pigs, median survival time (MST) correlated with both dose and trough levels (ng/ml). All kidneys had some degree of rejection seen on necropsy. After rejection, pneumonia was the most common cause of death. No specific end-organ toxicity was noted on histopathologic examination. Triglyceride and cholesterol levels increased in all treated pigs (both rapamycin and triple therapy) vs. untreated controls--however, all values were within normal limits. Mean ALT levels increased in weeks 2 to 4 in the higher-dose rapamycin groups but returned to baseline in pigs surviving after the drug was stopped. ALT levels did not increase above twice normal in any group. Creatinine levels correlated with the degree of rejection seen on biopsy. We noted no other toxicities. We conclude that rapamycin, given as oral monotherapy, is an effective and safe immunosuppressant in our large animal renal allograft model. Outcome correlated with dose and whole-blood levels.

Spontaneous renal disease in beaver in Louisiana.

Interstitial nephritis was present in 13 of 25 adult beavers (Castor canadensis). Results of serum chemistry, serotyping, and culture for leptospires were compared with the extent of renal lesions. Although the pathogenesis of the nephritis was not determined, the survey provided baseline information on spontaneous renal disease in beavers.

Poditis in the rat as a complication of experiments in exercise physiology.

Experiments using the rat to study the effect of forced exercise on various physiologic and biochemical processes were complicated by the occurrence of poditis. Staphylococcus aureus was isolated from two affected rats and a tentative diagnosis of staphylococcal pododermatitis was made. In a subsequent study, poditis again occurred and S aureus was isolated from the rats, cages, exercise wheels, and attendants. Subcutaneous inoculation of six rats with the organism failed to reproduce the disease. The isolation of S aureus, and the apparent response to hygienic and therapeutic procedures and a change in exercise apparatus, suggested a traumatic and infectious etiology. However, the respective roles of trauma and S aureus or other microorganisms were not resolved.

Effect of length of treatment with Bayer 2502 on isolation of Trypanosoma cruzi and resistance to challenge in the mouse.

The effect of length of treatment of Trypanosoma cruzi with Bayer 2502 (Bay 2502, Lampit, Nifurtimox) on resistance to challenge and parasite isolation was studied in two experiments. In each, 200 mice were divided into groups of 20, infected with T. cruzi, and then treated with Bay 2502 for 1 to 8 consecutive weeks. Sixteen weeks after exposure, 10 mice from each experimental group were challenged with 150,000 trypomastigotes. The remainder were maintaned for 8 more weeks and killed for isolation of parasites. Mice treated with Bay 2502 for up to 8 consecutive weeks were uniformly resistant to challenge, and parasites could not be isolated from groups treatef for over 6 weeks. Results suggest that prolonged treatment with Bay 2502 eliminates T. cruzi from infected hosts and that resistance to challenge is not dependent on the presence of the organisms in mice.