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Biomedical subjects

R Oishi

Publications and source records attributed to R Oishi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Micellar electrokinetic capillary chromatography for therapeutic drug monitoring of zonisamide.

The simultaneous determination of zonisamide, a new type of antiepileptic drug, and the typical antiepileptic drugs phenobarbital, phenytoin and carbamazepine in human serum was developed using micellar electrokinetic capillary chromatography (MECC) with a diode array detector. A high correlation was revealed between the zonisamide levels in human serum obtained by MECC and those obtained by high-performance liquid chromatography (r=0.981). The serum levels of phenobarbital, phenytoin and carbamazepine determined by MECC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MECC analysis was appropriate for the intra- and inter-day assay coefficients. Therefore, the MECC method established here could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs in patients, especially those treated with a combination of zonisamide and other antiepileptic drugs.

Anticonvulsants↗
PubMed1997

Repeated interferon-alpha administration inhibits dopaminergic neural activity in the mouse brain.

In vivo effects of single and repeated interferon-alpha administrations on the dynamics of noradrenaline, dopamine and 5-hydroxytryptamine were investigated in the mouse brain. Single interferon-alpha administration (15, 30 and 60 X 10(6) U/kg i.p.) had no significant effect on the levels of monoamines and their metabolites or monoamine turnover. When interferon-alpha (15 X 10(6) U/kg i.p.) was administered once a day for 5 days, however, both dopamine and 3,4-dihydroxyphenylacetic acid levels were significantly decreased and alpha-methyl-p-tyrosine-induced dopamine depletion was significantly suppressed. These results suggest that repeated interferon-alpha administration inhibits dopaminergic neural activity. This inhibitory action of interferon-alpha in dopamine neurons may be involved in adverse central effects, such as parkinsonism and depression with suicidal potential.

Animals↗
PubMed1997

Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.

The effects of nicotinic and beta-adrenergic receptor antagonists on tail-tremor induced by repeated nicotine administration were investigated in rats. The daily administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repeated administration of dimethyl phenyl piperazinium iodide (1 mg/kg/day, s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each day, abolished the tail-tremor. After discontinuation of the mecamylamine treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20 mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group. Neither carteolol (20 mg/kg, i.p.) nor metoprolol (20 mg/kg, i.p.) treatment showed such effects. Intraspinal injection of 6-hydroxydopamine markedly enhanced the tail-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by propranolol (5-20 mg/kg, s.c.) in a dose-dependent manner. These results suggest that central nicotinic receptors are essential for the onset and for the further development of tail-tremor induced by the repeated administration of nicotine, and that beta 2-adrenoceptors are associated with the tremor mechanism. Moreover, spinal noradrenergic mechanisms may be involved in the manifestation of this phenomenon.

Adrenergic Agents↗
PubMed1997

Enhancement by morphine of radiographic contrast media-induced histamine release in rat peritoneal mast cells.

In intravascular application of radiographic contrast media causes hypersensitivity reactions, in which histamine release may play a major role. We examined the interaction between contrast medium and morphine. Among the four nonionic contrast media examined, iopamidol showed the most marked histamine release from rat peritoneal mast cells in vitro. Although iopamidol and morphine themselves did not induce histamine release at concentrations up to 65 mgI/ml and 3 mM, respectively, their combination resulted in a significant histamine release. These findings suggest that patients with exposure to medicines that induce histamine release may have a higher incidence and severity of hypersensitivity reactions to radiographic contrast media.

Animals↗
PubMed1997

Pharmacokinetics of thiamylal enantiomers in humans.

Thiamylal, a chiral thiobarbiturate, is marketed as the racemate. The pharmacokinetic behavior of thiamylal enantiomers was studied in patients undergoing thiamylal treatment. The percentage of R(+)-thiamylal unbound to serum protein was 1.5 times greater than that of S(-)-enantiomer (17.5 +/- 2.6% and 11.7 +/- 2.0% mean +/- SD, p < 0.001, n = 7). The pharmacokinetic parameters of enantiomers were estimated in 6 patients. S(-)-thiamylal serum concentration was higher than R(+)-enantiomer in all patients at all time points examined. Total clearance of R(+)-thiamylal (0.27 +/- 0.23 1/hr/kg) was 1.8 times greater (p < 0.05) than that of S(-)-thiamylal (0.15 +/- 0.13). The volume of distribution at steady state of R(+)-thiamylal (3.66 +/- 1.99 l/kg) was 1.4 times higher (p < 0.05) than that of S(-)-enantiomer (2.60 +/- 1.35). The differences in these parameters may be due mainly to enantioselective binding to serum protein.

Adult↗
PubMed1997

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↗
PubMed1996

In-line filter occlusion during intravenous delivery of injectable menatetrenone (vitamin K2).

Filter occlusion during intravenous infusion of injectable menatetrenone in an electrolyte fluid was examined. The menatetrenone concentration and its emulsion droplet size were not changed by in-line filtration. However, particle counts in the admixed solution and examination of scanning electron micrographs of the surface of the filter membrane indicated that particle formation occurred immediately after the admixture of menatetrenone injection with Hicaliq No. 2, but not with 5% glucose injection. This may be due to the interaction of excess lecithin in the emulsion with the electrolyte. Filter occlusion also occurred with the admixture of menatetrenone-free emulsion and Hicaliq No. 2, but not with 5% glucose injection. These findings indicate that injectable menatetrenone should not be admixed with electrolyte fluids.

Drug Therapy, Combination↗
PubMed1996

Instability of standard calibrators may be involved in overestimating vancomycin concentrations determined by fluorescence polarization immunoassay.

Fluorescence polarization immunoassay (FPIA) is widely used to determine serum vancomycin concentrations, and it has been shown to over-estimate vancomycin concentrations in sera from renally impaired patients. This phenomenon has generally been thought to result from interference by vancomycin crystalline degradation products (CDP-1). In this study, we confirmed that serum vancomycin concentrations in various patients determined by FPIA were higher than those determined by high-performance liquid chromatography (HPLC) or enzyme multiplied immunoassay (EMIT). However, the quantitative differences in the serum vancomycin concentrations determined by FPIA versus HPLC were higher than the CDP-1 concentrations, even when the cross-reactivity of FPIA to CDP-1 is assumed to be 100%. When the vancomycin calibrators for FPIA were stored at 4 degrees C for 30 days, their concentrations determined by FPIA and HPLC decreased by 14 and 20%, respectively, and CDP-1 corresponding to 20% of primary vancomycin was formed. When stored at 25 degrees C, the degradation of vancomycin was more marked. We concluded that not only the cross-reactivity of FPIA to CDP-1 but also the instability of calibrators may cause the overestimation of serum vancomycin concentrations determined by FPIA.

Aged↗
PubMed1996

Potentiation of L-dopa-induced behavioral excitement by histamine H1-receptor antagonists in mice.

Effects of histamine H1-receptor antagonists on L-dopa-induced behavioral excitement were examined in mice to confirm behaviorally the inhibition of dopamine uptake by these compounds. L-Dopa (100-300 mg/kg, s.c.) combined with pargyline hydrochloride (80 mg/kg, i.p.) caused a dose-dependent behavioral excitement. The marked excitement induced by L-dopa (300 mg/kg) plus pargyline was significantly inhibited by pimozide (0.1 - 1 mg/kg, s.c.), a selective dopamine antagonist. Tripelennamine (10 mg/kg, s.c.), d-chlorpheniramine (1 and 2 mg/kg, s.c.), homochlorcyclizine (2 and 5 mg/kg, s.c.), diphenhydramine (2 and 5 mg/kg, s.c.) and mepyramine (2 and 5 mg/kg, s.c.) each markedly enhanced the moderate behavioral excitement induced by L-dopa (150 mg/kg) plus pargyline. These findings are behavioral evidence for inhibition of dopamine uptake by H1 antagonists, which has been suggested by neurochemical studies.

Animals↗
PubMed1996

Relapse and elevation of blood urea nitrogen in acute fenitrothion and malathion poisoning.

We observed 6 patients with severe fenitrothion and/or malathion poisoning necessitating artificial ventilation and intensive care monitoring. Three developed relapse following acute cholinergic crisis. In these patients the blood urea nitrogen (BUN) abnormally elevated before the development of relapse and the initial high concentration of plasma organophosphate (OP) decreased only gradually. However, the patients who did not develop relapse showed no elevation of BUN and a relatively low concentration of plasma OP. This observation was confirmed in a retrospective search of 14 patients. In addition, erythrocyte cholinesterase (EChE) activities were more helpful to diagnose the development of relapse than plasma cholinesterase activities. Therefore, careful monitoring of BUN in addition to plasma OP concentration may be useful to predict the development of relapse.

Blood Urea Nitrogen↗
PubMed1996

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↗
PubMed1995

Rapid and sensitive detection of benzodiazepines and zopiclone in serum using high-performance thin-layer chromatography.

We developed a rapid and sensitive method of identifying benzodiazepines and zopiclone in human serum using high-performance thin-layer chromatography (HPTLC). These drugs were developed and separated on plates within 8-11 min and detected by means of UV radiation and colour. Each drug was accurately identified by means of the values of RF x 100 and the spot colour in three systems. The detection limit of the benzodiazepines in serum was 0.1-0.4 micrograms/ml, except for cloxazolam and haloxazolam. The sensitivity was increased about ten-fold over the conventional method. These results suggested that the HPTLC system is useful for the initial detection and identification of these drugs in emergencies.

Azabicyclo Compounds↗
PubMed1995

Enantioselective determination of thiamylal in human serum by high-performance liquid chromatography.

Thiamylal, a widely used anesthetic drug, has two enantiomers. We developed a novel and simple method for measuring thiamylal enantiomers in human serum using reversed-phase high-performance liquid chromatography. R(+)- and S(-)-Thiamylal were separated using a chiral mobile phase containing beta-cyclodextrin, and detected at the range of 50 ng/ml-25 micrograms/ml in serum. The relative standard deviations of R(+)- and S(-)-thiamylal were 3.4-8.7% and 2.8-8.7% for the intra-day assay, and 2.8-12.0% and 2.8-13.0% for the inter-day assay. This method may be applied to enantioselective pharmacokinetic studies of thiamylal.

Chromatography, High Pressure Liquid↗
PubMed1995

Anticonflict effects of acute and chronic treatments with buspirone and gepirone in rats.

The anticonflict activities of buspirone and gepirone were examined in the Vogel's water licking test in rats. Acute treatment with buspirone induced a significant increase in water licking response, but gepirone showed slightly more marked effect than buspirone. The anticonflict activities of these compounds were potentiated by chronic administration. Especially, gepirone exhibited a dramatically remarkable anticonflict effect. These results suggest that gepirone has a great possibility of promising drug for anxiety.

Animals↗
PubMed1995

Vitamin K prodrugs: 2. water-soluble prodrugs of menahydroquinone-4 for systemic site-specific delivery.

PURPOSE: The hydrochloride salts of the N,N-dimethylglycine esters of menahydroquinone-4 (1-mono, 1; 4-mono, 2; and 1,4-bis, 3) were assessed in vivo as prodrug for the systemic site-specific delivery system of menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4, vitamin K2(20)). METHODS: The disposition of MK-4 and menaquinone-4 epoxide (MKO) following the intravenous administration of the prodrugs and MK-4 preparation solubilized with surfactant (H-MK-4) were studied in vitamin K cycle inhibited rats. The relative bioavailability of MKH after the administration of the prodrugs was assessed from the area under the plasma concentration of MKO vs. time curve (AUCMKO). The specific delivery of MKH to its active site (liver) and coagulation activity after the administration of selected prodrug 1 were then compared with those of H-MK-4 in warfarin poisoned rats. RESULTS: All compounds showed linear pharmacokinetics, and significant bioavailability of MKH was also observed following the administration of 1 (188%), 2 (87%) and 3 (135%). Prodrug 1 caused the following increases; AUCliver of MKO from 70.7 +/- 5.77 (H-MK-4) to 167 +/- 7.89 nmol.h/g, MRTliver of MKO, from 3.87 +/- 0.307 to 8.57 +/- 0.432 h. The liver accumulation of intrinsic 1 reached a maximum (88% of dose) by 0.25 h. The rapid and liver-selective uptake and liver esterase mediated MKH regeneration characteristics of 1 enhanced the delivery of MKH to its active site and the selective advantage was increased 5.7 fold. The coagulation activity was extended 1.9 fold by 1 administration. CONCLUSIONS: The results indicated that these highly water-soluble and liver-esterase hydrolyzable ester derivatives of MKH are potential candidates for parenteral prodrugs which can thus achieve the systemic site-specific delivery of MKH. Such effective and selective delivery of MKH to its active site can therefore lead to enhanced pharmacological efficacy and can also avoid the toxicity induced by the solubilizing agent used in the H-MK-4 preparation.

Animals↗
PubMed1995

Influences of immobilization and footshock stress on pharmacokinetics of theophylline and caffeine in rats.

The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg-1) and caffeine (30 mg kg-1) administered orally were examined in rats. The immobilization stress for 30 min or 1 h immediately after oral administration caused marked immobilization period-related decreases in plasma theophylline concentrations during the absorption phase, but did not affect plasma caffeine concentrations. The ka and Cmax values for theophylline were significantly decreased, and the tmax was significantly increased. On the other hand, when the immobilization stress was loaded for 1 or 3 h before the oral administration, the plasma theophylline or caffeine concentrations were not affected. The footshock stress for 30 min immediately after oral administration did not significantly decrease plasma theophylline concentrations during the absorption phase. These results suggest that the pharmacokinetics of theophylline are influenced by strong stress, possibly due to the inhibition of its absorption from the gastrointestinal tract, but the pharmacokinetics of caffeine are not influenced by stress, probably due to its central action.

Animals↗
PubMed1995

Quality evaluation of commercial lyophilized human growth hormone preparations.

The quality of three commercial injections (Genotropin, Humatrope and Norditropin) of lyophilized recombinant human growth hormone (r-hGH) was evaluated in tests by visual inspection, high-performance gel permeation chromatography, polyacrylamide gel electrophoresis, scanning electron microscopy and energy dispersion X-ray microanalysis. The influence of the reconstitution method on gel formation was examined as follows: rapid injection of the diluting solution into a vial against the wall, slow injection onto the surface of the content, and rapid injection onto the surface of the content. The degree of gel formation differed among reconstitution methods. Moreover, fibrous particulate matter in addition to degradation products of r-hGH were evident in all preparations. The quality of r-hGH injection differed among commercial products. Norditropin included the least particulate matter when examined immediately after reconstitution, but it was easily denatured after storage in solution. We advise medical specialists to reconstitute a preparation by the optimal method.

Drug Compounding↗