Establishment of a model of acetaminophen-induced hepatotoxicity in different weekly-aged ICR mice.

Acetaminophen (APAP), a widely used analgesic and antipyretic drug, has the potential to cause lethal hepatotoxicity. Mice are widely used for developing murine models of APAP-induced hepatotoxicity, and many researchers have used these models for APAP-related studies including the fields of biology, pharmacology and toxicology. Although drug-induced hepatotoxicity is dependent on a number of factors (species, gender and age), very few studies have investigated the effect of aging on APAP hepatotoxicity. In this study, we evaluated the effect of age on APAP-induced hepatotoxicity in different weekly-aged mice to establish a model of APAP-induced hepatotoxicity that is an accurate reflection of general experimental conditions. Male ICR mice 4, 6, 8, 10 and 12 weeks old were given APAP intraperitoneally, and mortality, hepatic damage and the plasma concentration of APAP metabolites were evaluated. It was found that younger male ICR mice were relatively resistant to hepatotoxicity induced by intraperitoneal APAP administration. In addition, the APAP-glucuronide concentration in plasma remained essentially the same among the differently-aged mice, while APAP-sulfate levels were dramatically decreased in an age-dependent manner. Thus, it is recommended that mice of the same ages be used in studies related to APAP-induced hepatotoxixity. These results provide evidence in support of not only the age-related changes in susceptibility to APAP-derived hepatotoxicity in mice but also in developing mouse models for APAP-related studies.

Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy.

AIMS: Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients. METHODS: The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole. RESULTS: The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006). CONCLUSION: Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate.

Cultural differences in attitudes, values, and beliefs about osteoporosis in first and second generation Japanese-American women.

This study examines attitudinal differences related to osteoporosis between first and second generation Japanese-American women. In an interview, the women completed a battery of tests assessing their attitudes, values, and beliefs about the diagnosis, treatment, and follow-up care of osteoporosis. The groups differed in their general knowledge of osteoporosis, perceptions of the disease, attributions of its causes, anticipated and preferred support mechanisms for care, and anticipated areas of concern for self-or other-care. There were also considerable differences in treatment compliance and feelings toward physicians. The findings were discussed in relation to the effects of culture on health-care attitudes and behaviors.

(+-)-1-Amino-1,3-cyclopentane-trans-dicarboxylic acid (trans-ACPD) induced inositol triphosphoric acid formation in the brain of iron-induced epileptic rats and epileptic El mice.

Myo-inositol-1,4,5-triphosphoric acid (IP3) formation stimulated by (+-)-1-amino-1,3-cyclopentane-trans-dicarboxylic acid (trans-ACPD) was examined in the cortex, hippocampus and cerebellum of iron-induced epileptic rats and epileptic El mice. Increased IP3 formation by trans-ACPD was observed in the cortex, hippocampus and cerebellum of iron-injected rats while it was found in the hippocampus and cerebellum of the saline-injected control rats. Increased IP3 formation by trans-ACPD was remarkably higher in the hippocampus of iron-injected rats than the other regions. Increased IP3 formation by trans-ACPD was observed in the cortex, hippocampus and cerebellum of ddY mice, while such an increase was found only in the cerebral cortex and not in the hippocampus and cerebellum of El mice. These findings suggest that the inositol response may be involved in the seizure mechanisms of iron-induced epileptic rats and epileptic El mice in some different forms.

Probucol scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited formation of thiobarbituric acid reactive substances.

Probucol is suggested to have antioxidant properties. The direct scavenging action of probucol on hydroxyl radicals, superoxide and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were examined using electron spin resonance (ESR) spectrometry. Probucol scavenged DPPH radicals dose dependently but showed no effect on hydroxyl radicals and superoxide generated by Fenton reaction and by hypoxanthine-xanthine oxidase system, respectively. It inhibited the formation of thiobarbituric acid reactive substances (TBARS) in rat cortex homogenate induced by ascorbic acid and FeCl2 at low dose, but it increased TBARS formation at high doses. Probucol showed no effect on the carbon centered radicals. Iron injection into the rat cortex, which is an experimental model for traumatic epilepsy, increased TBARS level in the cortex, hippocampus, striatum and cerebellum, but pretreatment with probucol inhibited the increase in these brain parts except for the hippocampus. These results suggest that the antioxidant property of probucol is partly due to its free radical scavenging effect.