Fifty-five pregnant BALB/c mice received various doses of Brucella abortus virulent strain 2308 intraperitoneally on day 9 of gestation, and uteri and spleens were examined at 3, 5, 7, and 9 days post-inoculation to study the pathogenesis of infection. A dose of 10(5.7) B. abortus organisms produced a severe, necrosuppurative placentitis. Bacteria multiplied preferentially within the placenta and were identified within the rough endoplasmic reticulum of trophoblast giant cells and within the visceral yolk sac endoderm. Abortions did not occur, but infarction of the labyrinth region of severely affected placentas occasionally resulted in fetal death. The severity of infection in the spleens of nonpregnant mice receiving the same challenge dose was not significantly different from that in the spleens of challenged pregnant mice. These results suggest that the sensitivity of the pregnant mouse to placental brucellosis is not due to a generalized immunosuppression but rather may involve a combination of local suppression of the immune response and a susceptible cell population suitable for Brucella colonization and replication. Experimental murine brucellosis resembles ruminant brucellosis and provides a model to study the intracellular replication of B. abortus in trophoblasts.

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Military use of depleted uranium (DU) has renewed interest in the toxicology of this metal. In this study, the nephrotoxicity of single exposure DU was assessed with and without pre-exposure stress. Adult male Sprague-Dawley rats (n=288) were administered a single IM dose of 0, 0.1, 0.3 or 1.0 mg/kg DU. Corticosterone concentrations (ng/ml, mean+/-SD) were 763.65+/-130.94 and 189.80+/-90.81 for swim stressed and unstressed rats. Serum and kidney uranium concentration, hematocrit, chemistry, and renal histology were assessed on sacrifice days 1, 3, 7 and 30 post-DU-dosing. Dose related increases in serum and kidney uranium were noted. DU concentration peaked day 1 in the kidney and days 3-7, in the serum. Dose-related elevations of Cr and BUN concentrations were seen on days 3 and 7. A decline in serum albumin coincided with Cr and BUN suggesting protein losing nephropathy. Dose related acute tubular necrosis and proliferative glomulonephritis were seen. Tubular regeneration in low dose rats was almost complete by day 30. High dose rats had extensive tubular necrosis and delayed regeneration with focal residual chronic interstitial nephritis and cortical scarring. Glomular changes were reversed in all treatment groups by day 30. Stress exposure had no impact on any measured renal parameter.