In this study, a high-performance liquid chromatographic method including a treatment with ion exchange resin following a deproteinization treatment, was studied for determination of cephaloridine in the rat urine which was contaminated by pieces of feces and diet pellets. The solvent system used Was 10% acetonitrile (v/v) in 0.1 M K2 HPO4 -H3 PO4 buffer, pH 7.5, and this was isocratically eluted on a reversed-phase column of NOVA-PAK C18. The urine sample containing cephaloridine was deproteinized, treated with a strongly basic anion exchange resin of Dowex-1-Chloride, and then chromatographed. In comparison to the sample treated by the simple deproteinization, the residual substances after the deproteinization, which interfered the cephaloridine peak, were removed by the following treatment with Dowex-1-Chloride, as was confirmed using a three-dimensional computing spectrophotometric monitor. Thus, the present method is considered to be useful in determination of cephaloridine in such body fluids as urine in which many interfering substances are contained.
Age-related alterations in bone marrow cellularity were ex-amined on SD and Wistar SPF rats. Six rats / strain / sex were sacrificed at 58, 83, 109 and 123 or 135 weeks of age and quantitative assessment and categorization of the bone marrow cells were performed. One male and two female SD rats suffering from leukemia were excluded from statistics. Age-related increases of myeloblasts and plasma cells were observed in rats of either strain and either sex. Age-related decreases in percentages of lymphocytes were noticed in SD, but not in Wistar rats. Age-related alterations in absolute numbers of marrow lymphocytes were equivocal in either strain.
In the present paper we report the effect of high doses of temazepam on drug-metabolism induction in rat and mouse. Temazepam induced a dose-dependent and reversible increase of hepatic microsomal drug-metabolizing enzymes in the rat, dose-correlated increase of dimethadione / trimethadione ratios in plasma of the rat, and dose-related shortening of hexobarbital-induced sleeping time in the mouse. In this study trimethadione is considered a good indicator for estimating the state of hepatic enzyme induction.
The concentration of malondialdehyde (MDA) in tissues in paraquat poisoning was compared between humans and rats. Lung MDA increased in humans, but not in rats despite of development of histological change of the lung. On the other hand, liver MDA increased both in humans and in rats. These findings suggest that lipid peroxidation may not be primary mechanism of paraquat toxicity.
For long-term toxicological studies, mizoribine at the dose of 2.5 mg/kg body weight was administered orally to two male and two female Beagle dogs for 36 consecutive months, once a day, 6 days a week, with a day-off on the 7th of each week. As a control group, 2 male and 2 female dogs were kept under the same conditions as the treated group. The above experiment resulted in no abnormal general symptoms being found in either group. In addition, body weight gain instead of weight loss was observed in both groups. Moreover, hematological and biological parameters were in the normal range, and no statistical difference was obtained between the two groups. An additional 10 mg/kg of mizoribine was administered once to both groups at the months of 6, 12, 18, 24, or 36 after the onset of this toxicological study so as to determine the pharmacokinetic behavior of serum mizoribine. This resulted in no significant difference being observed between the two groups. Therefore, it can be inferred that accumulation of mizoribine is not induced by its long-term repeated administration. In fertility study, the analysis of the sperm and the mating ability of a male dog with an appropriate healthy female dog revealed that mizoribine at this dose did not provoke any abnormalities in male gonadal functions.
Four Beagle dogs were administrated with mizoribine 2.5 mg/kg/day for 36 months. Clinical and laboratory findings were fully described in the first report, in which no remarkable abnormalities were detected. Visceral organs of the experimental group and non-treated control group were submitted for pathological investigations. No conspicuous macroscopical and microscopical drug-induced changes were disclosed in the experimental group.