Shiga-like toxin-producing Escherichia coli (STEC) infection causes diarrhea, which is often bloody and which can result in potentially life-threatening hemolytic-uremic syndrome (HUS). Urtoxazumab, a humanized monoclonal antibody directed against the Shiga-like toxin 2 (Stx2) produced by STEC, has been developed as a promising agent for the prevention of HUS. Single randomized, intravenous, double-blind, placebo-controlled doses of urtoxazumab were administered to assess its safety and pharmacokinetics in healthy adults (0.1 to 3.0 mg/kg of body weight) and STEC-infected pediatric patients (1.0 and 3.0 mg/kg). No dose-related safety trends were noted, nor were antiurtoxazumab antibodies detected. The disposition of urtoxazumab showed a biexponential decline, regardless of the dose. In healthy adults, the mean terminal elimination half-life was consistent across the dose groups and ranged from 24.6 days (3.0-mg/kg dose group) to 28.9 days (0.3-mg/kg dose group). The mean maximum serum drug concentration (C max ) ranged from 2.6 g/ml at 0.1 mg/kg to 71.7 g/ml at 3.0 mg/kg. The disposition of urtoxazumab following the administration of doses of 1.0 and 3.0 mg/kg in pediatric patients showed mean C max s of 19.6 and 56.1 g/ml, respectively. Urtoxazumab was well tolerated, appears to be safe at doses of up to 3.0 mg/kg, and is a potential candidate for the prevention of HUS in pediatric patients.

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Using food-deprived rabbits we investigated the effects of nutritional deficiency on the development of pressure sores. The body weight of these animals was decreased significantly from normal. Organ weights of liver, heart, spleen, kidney, and testis were significantly decreased from normal as well. Protein deficiency in these animals was indicated by serum tests, as well as by histologic features of liver and testis and ultrastructural findings on fibroblasts. We produced lesions in malnourished as well as normal rabbits by exposing their skin to a balloon-produced compressive force of 120 +/- 10 mmHg for 4 hours. Biopsies were taken 1, 2, and 3 days after the pressure application. Histologic findings at each time were as follows: At day one, the degree of ischemic skin destruction in the malnourished animals was more severe than that in the normal ones, and thrombi were occasionally seen in the malnourished cases. At day two, proliferation of fibroblasts and macrophage infiltration were evidenced in the normal animals, whereas signs of collagen fiber degeneration as well as microthrombi were seen in the malnourished ones. At three days, epidermal cells covered the lesions in the case of normal animals; however, massive necrosis of the epidermis was still recognized in the malnourished rabbits. Thus, the healing process of pressure sores was strongly suppressed in the malnourished animals. This suppression was attributed to the reduction in fibroblast proliferation, capillary formation, macrophage infiltration, and also to the low level of epidermal cell proliferation.

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The morphology of the parathyroid gland was examined in rats treated for one month with an active vitamin D3, 1α‐hydroxyvitamin D3. On continuous adiministration of 12.5 μg/kg/day of 1α‐hydroxyvitamin D3, the first histological change of the parathyroid gland, seen on day 10, was atrophy of the chief cells with marked accumulation of prosecretory granules. Replacement of the parenchyma by small or large cysts was evident on days 20 and 30. The remaining portion of the parathyroid parenchyma showed various histological changes: widened intercellular spaces intermingled with many cytoplasmic processes, shrinkage of the cytoplasm of the chief cells, and the presence of a few ghost cells in cysts. The appearance of cysts may be caused by suppression of parathyroid hormone secretion and is a characteristic lesion in hypervitaminosis in rats induced by treatment with active vitamin D3.