Several studies have investigated the effect of various anthropometric factors on the risk of cutaneous malignant melanoma (CMM). As the results are controversial, we analysed this issue in a case-control study conducted in Italy. The roles of several body size measures were investigated in a hospital-based case-control study of CMM conducted in Italy. The cases were 542 patients with CMM and the controls were 538 subjects admitted to the same hospitals as the cases for non-dermatological and non-neoplastic diseases. The odds ratios for the highest versus the lowest quartile were 2.06 [95% confidence interval (CI), 1.39-3.05] for weight, 1.16 (95% CI, 0.80-1.68) for height, 1.90 (95% CI, 1.28-2.80) for the body mass index (BMI) and 1.87 (95% CI, 1.28-2.72) for the body surface area (BSA). When allowing for BMI and BSA in the same model, the odds ratios were 1.55 (95% CI, 0.92-2.62) for BMI and 1.41 (95% CI, 0.85-2.33) for BSA. The present findings confirm that obesity increases the risk of CMM. BSA is also related to the risk of CMM. In terms of the population attributable risk, overweight and obesity would account for 31% of the cases of CMM in this Italian population, indicating the scope of prevention.
Endotoxins, cell wall components of bacteria, cause a number of biological effects, presumably via induction of potent cytokines. Previous research suggests that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its COOH-terminal tripeptide reduce the effects of cytokines. These molecules evoke antipyretic and anti-inflammatory effects in vivo. Localization of alpha-MSH within lymphocytes and recent observations that alpha-MSH receptors are widespread and that circulating alpha-MSH increases after systemic injection of endogenous pyrogen, a cytokine-containing extract, suggest that the peptide modulates host defense reactions. One aim of the present experiments was to learn whether a rise in circulating alpha-MSH occurs in synchrony with aspects of the acute phase response (APR) in conscious rabbits given endotoxin. A second aim was to learn whether administration of a single large dose of alpha-MSH inhibits all aspects of the APR induced by a low dose of endotoxin. The results indicate that the concentration of circulating alpha-MSH in rabbits does increase along with other changes in the APR (e.g., increase in corticosterone), which suggests that the peptide is widely available to modulate cytokine effects after endotoxin. Contrary to expectations based on previous results, a large dose of the peptide given intravenously inhibited only fever and not other aspects of the APR. The results suggest that the rise in circulating alpha-MSH is an aspect of the APR and that an acute increase in the circulating peptide caused by intravenous injection does not inhibit all other aspects of the host response to endotoxin.
Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg for 15 days and then at 0.75 mg/kg for another 15 days. After the 30-day dosing period, the treated monkeys were killed. Parameters monitored as markers for toxicity included body weight, food and water consumption, clinical observations, hematology, serum chemistry, light microscopy of all major organs (including brain and retina), and glial fibrillary acid protein immunohistochemistry. Domoic acid in serum and 24-hour urine samples was measured at several time points. All parameters measured remained unremarkable. Domoic acid concentrations measured in the 24-hour urine samples indicated that gastrointestinal absorption in the monkey was approximately 4-7 percent of the administered dose, which is at least twice that previously reported for the rat. Nat.
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