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Biomedical subjects

K Furuno

Publications and source records attributed to K Furuno.

At least 37 records · Page 2Linked to original sources

Cytotoxicity of food preservatives in cultured rat hepatocytes loaded with linolenic acid.

We investigated the ability of eight food preservatives to induce lipid peroxidation in normal and alpha-linolenic acid (LNA)-loaded cultured rat hepatocytes. On the addition of sodium dehydroacetate (DHA-Na), potassium sorbate (SA-K) or thiabendazole (TBZ) to the cell culture, lipid peroxidation, assessed in terms of the production of malondialdehyde (MDA), was induced in LNA-loaded cells, but not in normal cells. At the low concentrations, induction of lipid peroxidation in LNA-loaded cells was highest with TBZ, whereas at high concentrations DHA-Na greatly induced lipid peroxidation. The occurrence of lipid peroxidation in LNA-loaded cells was accompanied by a decrease in cellular GSH levels with the three preservatives and by a decrease in cellular protein-SH levels with DHA-Na and TBZ. Furthermore, cell injury, measured by the release of LDH, was produced in LNA-loaded cells exposed to DHA-Na and SA-K. The addition of TBZ caused substantial cell injury in normal cells, and even greater injury in LNA-loaded cells. The prevention of lipid peroxidation in LNA-loaded hepatocytes by addition of an antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD) almost completely prevented DHA-Na- and SA-K-induced cell injury, and reduced TBZ-induced cell injury. The addition of diphenyl (DP), o-phenylphenol (OPP) or butyl p-hydroxybenzoate (BHB) caused severe cell injury, in association with a marked decrease in cellular levels of both of GSH and protein-SH in both groups of cells. However, lipid peroxidation was not detectable in either group of cells exposed to these preservatives. Sodium propionate (PA-Na) and sodium benzoate (BA-Na) had little effect on any cytotoxic parameter in either group of cells.

Animals↗

Effects of various antiepileptic drugs on plasma levels of lamotrigine, a novel antiepileptic, in rats.

The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ), valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in rats. LTG plasma levels were measured by high-performance liquid chromatography (HPLC). A single oral administration of LTG at 2.5-10 mg/kg showed linear disposition kinetics. In the pharmacokinetic parameters of LTG when combined with CBZ, the maximal plasma concentration (Cmax) and the area under the plasma concentration curve (AUC0-36) values were significantly lower and the time to maximal plasma concentration (Tmax) value was significantly higher than those in LTG alone. Furthermore, the Cmax and AUC0-36 values of LTG when pretreated with CBZ for 7 days were significantly lower than those from simultaneous treatment with CBZ. The Cmax and AUC0-36 values of LTG when combined with VPA were significantly lower than those for LTG alone. There was no significant difference in the Tmax or time of elimination half-life (t1/2) values of LTG between simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG with ZNS combination, the Cmax value of LTG after long-term dosings of ZNS decreased significantly, whereas no significant change in Cmax was observed after the combined single administration of LTG and ZNS. Single and chronic ZNS treatment did not significantly affect the Tmax, t1/2 and AUC0-36 values of LTG. The LTG trough level was significantly reduced by CBZ administration, reached the bottom level at 6 days after starting CBZ administration, and recovered gradually after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes changes in the plasma LTG level. They also suggest that in therapy combining LTG with one of these antiepileptics, especially CBZ, the LTG concentration in plasma should be monitored carefully.

Administration, Oral↗

Influence of lactation on plasma phenobarbital concentrations in rats.

The effect of lactation on the pharmacokinetics of phenobarbital (PB) after delivery was studied in female rats. Non-pregnant animals received PB 20 mg/kg/day twice for 6-7 days before mating, during pregnancy and after delivery. Chronic PB did not significantly influence changes in the body weight of rats after delivery. On the first post-delivery day, the plasma PB concentration in the PB-treated rats was significantly higher than that in PB-treated, non-pregnant rats (non-pregnant rats); and thereafter, it gradually decreased until ablactation on the 20th day. After ablactation, plasma PB concentrations gradually returned to the level before delivery. In PB-treated rats, pharmacokinetic parameters (Cmax, AUC0-12) of PB between 0 and 12 hr after a single oral administration were significantly decreased during lactation. These results suggest that PB administered during lactation is transferred in part to offspring through maternal milk.

Administration, Oral↗

Effects of cigarette smoke inhalation on plasma diltiazem levels in rats.

A rapid and sensitive method for the assay of plasma diltiazem was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. The effects of cigarette smoke on plasma levels of orally administered diltiazem was investigated in rats. The animals were exposed to cigarette smoke for 10 min using a Hamburg II smoking machine, immediately after oral administration of diltiazem (10 mg/kg). In the nonsmoking nonrestrained rats, plasma diltiazem levels increased rapidly and reached the maximum (7.1 micrograms/kg) 2 h after administration and decreased gradually thereafter. In the nonsmoking restrained rats, plasma diltiazem levels increased rapidly, but showed almost constant levels between 1 h and 8 h after administration. The maximum level (5.4 micrograms/kg) was shown after 2 h. On the other hand, plasma diltiazem levels in the rats exposed to cigarette smoke reached the maximum (4.3 micrograms/kg) after 4 h. These results suggest that absorption of orally administered diltiazem is inhibited and delayed by cigarette smoke.

Animals↗

Pharmacokinetic evaluation of omeprazole suspension following oral administration in rats: effect of neutralization of gastric acid.

In order to evaluate a clinical use of omeprazole suspension, we examined the pharmacokinetics of omeprazole after oral administration in rats. Although the administration of omeprazole suspension buffered by NaHCO3 solution did not produce a significant increase in the area under the concentration-time curve (AUC) value compared with non-buffered group, the administration of NaHCO3 buffer immediately after dosing of omeprazole suspension buffered by NaHCO3 caused a significant increase in the AUC value. These results suggest that the NaHCO3 treatment following the administration of omeprazole buffered suspension effectively decreased the degradation of the compound by gastric acid. Therefore, the successive administration of NaHCO3 solution after the omeprazole dosing seems to be a simple and useful method for the administration to patients who cannot receive tablets.

Administration, Oral↗

Effects of nicotine and exposure to cigarette smoke on suppression of local graft-versus-host reaction induced by immobilization stress in mice.

To study the effects of emotional stress on immunological activities and modification of these effects by nicotine or cigarette smoke, we evaluated the effects of immobilization stress on local graft-versus-host (GVH) reaction, a cell-mediated immune response, and the effects of nicotine and cigarette smoke on them. The effects of immobilization stress on GVH reaction and the effects of nicotine and cigarette smoke on them were evaluated in two experiments: in Experiment 1 by applying the stimulations before and immediately after spleen cell transplantation, and in Experiment 2, by applying stimulations after transplantation. Spleen cells of BALB/C mice were injected into the footpad of CBF1 mice, and GVH reaction was examined after 7 days by weighing the popliteal lymph nodes. Immobilization, nicotine administration and inhalation of cigarette smoke were performed either for 5 days before and immediately after the transplantation (Experiment 1) or for 5 days after transplantation (Experiment 2). The weight of the lymph nodes was markedly increased in the control group, indicating GVH reaction, but the reaction was suppressed by immobilization in both experiments. This suppression of GVH reaction by immobilization was antagonized by nicotine administration and exposure to cigarette smoke in Experiment 1 but not in Experiment 2. These findings suggest that nicotine and cigarette smoke induce recovery of immune response suppressed by immobilization stress, especially by increasing the competence of antigen recognition.

Animals↗

Simple and rapid analysis of lamotrigine, a novel antiepileptic, in human serum by high-performance liquid chromatography using a solid-phase extraction technique.

A simple and rapid method for the quantitation of concentrations of lamotrigine, a novel antiepileptic, in human serum was developed with high-performance liquid chromatography, using a solid-phase extraction technique. The mobile phase was composed of acetonitrile-10 mM phosphate buffer (pH 3.5) containing 5 mM sodium octanesulphonate (27:73, v/v), and components were detected at 265 nm. Retention times of acetanilide as an internal standard and lamotrigine were 3.4 and 10.3 min, respectively. The coefficients of variation were 3.1-4.5% and 4.4-9.8% for the within-day and between-day precision estimates, respectively. The extraction recovery of lamotrigine added to blank serum was 86-107%. The quantitation limit of lamotrigine was ca. 0.2 microgram/ml in 100 microliters of serum. These results suggest that the method employed in this study is useful for the routine monitoring of serum concentrations of lamotrigine in epileptic patients.

Anticonvulsants↗