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To investigate whether supplementing manganese (Mn) to the maternal diet could reduce the deleterious effect of heat stress on the developing embryo, the hatchability, antioxidant status, and expression of heat shock proteins (HSP) were evaluated in chick embryos under normal and high incubation temperatures. A completely randomized design ( = 6) with 2 maternal dietary Mn treatments (unsupplemented control basal diet versus the basal diet + 120 mg Mn/kg as inorganic Mn) × 2 incubation temperatures (normal, 37.8°C, versus high, 39.0°C) was used. High incubation temperature did not affect (0.19) hatchability and embryo mortality and development but did increase (0.05) activities of heart manganese superoxide dismutase (MnSOD) and liver copper zinc superoxide dismutase and liver MnSOD mRNA and protein levels in embryos. High incubation temperature also decreased (0.003) HSP70 protein level in the heart but had no effects (0.07) in the liver of embryos. Maternal diet with Mn supplementation not only increased (0.05) the hatchability and Mn content (0.001) in the yolk and embryonic tissues and the activity of MnSOD in the heart (0.004) as well as relative liver weight (0.05) under normal incubation temperature but also decreased ( ≤ 0.05) embryo mortality and HSP90 mRNA level in the liver and heart of embryos. Furthermore, under high incubation temperature, maternal diet Mn supplementation increased (0.002) MnSOD protein expression in the liver of embryos but had no effect (0.43) under normal incubation temperature. These results indicated that high incubation temperature induced self-protective responses of chick embryos with a modification of antioxidant status and a depression of HSP70 protein level. Maternal dietary supplementation of Mn could improve the hatchability as well as antioxidant ability to protect against heat challenge in embryos during incubation.

An experiment was conducted to investigate the effects of environmental temperature and dietary Mn on egg production performance, egg quality, and some plasma biochemical traits of broiler breeders. A completely randomized factorial design involved 2 environmental temperatures (a normal temperature, 21 ± 1°C, and a high temperature, 32 ± 1°C) × 3 dietary Mn treatments (a Mn-unsupplemented corn–soybean meal basal diet or the basal diet supplemented with 120 mg of Mn/kg of diet as either MnSO4·H2O or manganese proteinate). There were 6 treatments with 6 replicates (4 birds per replicate). High temperature decreased egg weight (P0.0001), laying rate (P0.0001), egg yield (P0.0001), feed intake (P0.0001), egg:feed ratio (P0.0001), eggshell strength (P0.05) and thickness (P0.0001), plasma triiodothyronine level (P0.05), and alkaline phosphatase activity (P0.04) whereas it increased rectal temperature (P0.0001); plasma malondialdehyde level (P0.02); and activities (P0.002) of lactic dehydrogenase, aspartate aminotransferase, and creatine kinase. Broiler breeders fed the diets supplemented with Mn regardless of source had greater (P0.05) eggshell strength and lower (P ≤ 0.05) plasma triiodothyronine level and protein carbonyl content than those fed the control diet. The broiler breeders fed the diet supplemented with the organic Mn had greater (P0.01) eggshell thickness than those fed the control diet. There were interactions (P0.05) between environmental temperature and dietary Mn in laying rate, egg yield, feed intake, and egg:feed ratio. Under normal temperature, dietary Mn did not affect the above 4 parameters; however, under high temperature, broiler breeders fed the diet supplemented with the organic Mn showed greater (P0.03) improvements in these 4 parameters than those fed the control diet. The results from this study indicated that high temperature significantly impaired egg production performance and eggshell quality and induced lipid peroxidation and tissue damage whereas dietary supplementation of either organic or inorganic Mn improved eggshell strength and thermotolerance and reduced protein oxidation and that the organic Mn could alleviate the negative effect of high temperature on egg production performance of broiler breeders at the period of 32 to 45 wk of age.

Purpose To assess the pharmacokinetics (PK) of a human monoclonal antibody to IL-12 p40 (anti-IL-12 p40 mAb) following single intravenous (IV) infusion in patients with moderate to severe plaque-type psoriasis as part of a Phase I study. Methods. Patients (n = 18) were randomly assigned to receive a single ascending IV dose of the mAb (n = 4–5 per group). Blood samples were collected and serum mAb levels were measured using an ELISA method. Non-compartmental analysis was employed to calculate the PK parameters of the mAb. The relationship between PK and the severity of psoriatic lesions (Psoriasis Area and Severity Index, PASI) was also investigated to explore the relationship between drug exposure and efficacy. Results. The mAb was slowly eliminated from the circulation after a single IV infusion. The Cmax and AUC were linearly correlated with the dose. Dose-dependent sustained improvements in PASI were observed. Conclusions. PK of the mAb following a single IV infusion were linear and dose-independent, and the systemic exposure increased in a dose-proportional manner. IV administration to patients is feasible in terms of its favorable elimination half-life and sustained clinical response. Clinical Pharmacology & Therapeutics (2004) 75, P9–P9; doi: 10.1016/j.clpt.2003.11.034