Biomedical subjects

R Oishi

Publications and source records attributed to R Oishi.

At least 73 records · Page 4Linked to original sources

PubMed1995

Effect of pregnancy on plasma phenobarbital concentrations in rats.

We examined the pharmacokinetics of phenobarbital before and during pregnancy in rats. Animals were divided into four groups: (a) control, (b) pregnant, (c) phenobarbital-treated, and (d) phenobarbital-treated pregnant groups. The increase in body weight of nonpregnant or pregnant rats was not influenced by long-term phenobarbital treatment. Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affected by pregnancy. Furthermore, pregnancy did not affect pharmacokinetic parameters of phenobarbital between 0.25 and 24h after administration. These results suggest that pregnancy does not influence on the pharmacokinetics of long-term phenobarbital treatment at a fixed dosage by body weight.

Animals↗

PubMed1995

Acute organophosphate poisoning after disulfoton ingestion.

A 75-year-old woman attempted suicide by ingesting a large quantity of granular Di-Syston which is an organophosphate insecticide containing 5% disulfoton (ethylthiometon). On admission, the total plasma phosphorodithioate sulfone concentration (disulfoton and its metabolites, phosphorodithioate sulfoxide and its sulfone) determined by gas chromatography was 1095 ng/mL. After gastric lavage, the concentration gradually decreased to 505 ng/mL. However, it began to increase again 20 h after admission and reached the peak concentration (1322 ng/mL) at 56 h. It was concluded that the secondary elevation of the plasma concentration was due to the prolonged absorption of the organophosphate from the residual granules in the stomach, despite the early gastric lavage. Pralidoxime iodide administration temporarily restored erythrocyte cholinesterase activity to almost normal and inhibited the excessive, delayed reduction of cholinesterase activity. It is recommended that poisoning with the granular form of disulfoton should be treated with repetitive or prolonged gastric and intestinal lavage, charcoal, and a continuous intravenous infusion of pralidoxime iodide in addition to atropine sulfate.

Aged↗

PubMed1995

[Survey of using conditions of sterilized and non-sterilized disinfectants in Kyushu University Hospital].

We surveyed the using conditions of sterilized and non-sterilized disinfectants in Kyushu University Hospital by questionnaires and direct hearing. The kinds and concentrations of disinfectants used were generally proper for their respective purposes. However, there were also some inappropriate cases, such as the cleansing of mucosal membranes with chlorhexidine (Hibitane) gluconate and uses of the concentrations different from those described in the package insert. The present survey was very useful for proper uses of disinfectants.

Disinfectants↗

PubMed1994

Simple and sensitive assay of zonisamide in human serum by high-performance liquid chromatography using a solid-phase extraction technique.

A rapid and sensitive method for the assay of zonisamide in serum was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. A 20-microliter volume of human serum was first purified with a Bond-Elut cartridge column. Then, the methanol eluate was injected onto a reversed-phase HPLC column with a UV detector. The mobile phase was acetonitrile-methanol-distilled water (17:20:63, v/v) and the detection wavelength was 246 nm. The detection limit was 0.1 micrograms/ml in serum. The coefficients of variation were 4.2-5.6% and 5.1-9.1% for the within-day and between-day assays, respectively. This method can be used for clinical pharmacokinetic studies of zonisamide in serum even in infant patients with epilepsy.

Anticonvulsants↗

PubMed1994

First-pass metabolism of omeprazole in rats.

To clarify the in vivo first-pass metabolism of omeprazole, the pharmacokinetics were examined after oral, intraduodenal (i.d.), intraportal venous (i.p.v), and intravenous (i.v.) administration at various doses to rats. Extraction ratios in the liver and intestinal tract were determined from the areas under the concentration-time curve (AUC) for i.p.v. and i.v. administration and from those for id and ipv administration, respectively. Assuming that the drug was absorbed from the gastrointestinal tract completely, the hepatic and intestinal extraction ratios were 0.80, 0.63, and 0.59 at doses of 2.5, 5, and 10 mg/kg and 0.70 and 0.73 at doses of 5 and 10 mg/kg, respectively. The bioavailability of orally administered omeprazole was 6.4, 9.6, and 12.6% at the doses of 10, 20, and 40 mg/kg, respectively. There were no differences in the distribution volume of steady state, total clearance, or elimination half-life at any doses. In addition, the AUC value after oral administration (20 mg/kg) in rats acutely intoxicated with CCl4 was 2.4 times larger than that in the control. These findings suggest that omeprazole undergoes a first-pass metabolism in the intestinal mucosa and/or lumen, as well as in the liver, and that the major contribution to the dose-dependent increase in bioavailability is a saturation of the first-pass metabolism in the liver.

Administration, Oral↗

PubMed1994

Simultaneous determination of primidone and its active metabolites in rat plasma by high-performance liquid chromatography using a solid-phase extraction technique.

Primidone (PRM) and its active metabolites, phenylethylmalonamide (PEMA) and phenobarbital (PB), in rat plasma were simultaneously determined using a solid-phase extraction technique followed by high-performance liquid chromatography (HPLC). Twenty microliters of plasma was applied to a Bond-Elut C-18 cartridge column with 0.1 microgram of acetanilide (internal standard, IS). After the column was washed, PRM, PEMA, PB, and IS were eluted with methanol and injected into the HPLC system. Calibrations for these substances were linear in the range of 0-20 micrograms/mL. The coefficients of variation were 1.5-7.9% and 3.4-9.1% in the within-day and between-day assays, respectively. The recovery rates were 96.8-101.8%. The pharmacokinetics of these substances were examined after oral administration of PRM (50 mg/kg) to rats. The Tmax values for PRM, PEMA, and PB were 1.4, 5.7, and 6.6 h, respectively, and the Cmax values were 18.2, 8.1, and 9.6 micrograms/mL, respectively. This method is useful for pharmacokinetic studies of PRM and its active metabolites.

Administration, Oral↗

PubMed1994

Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain.

To compare in vivo effects of eleven compounds of different classes of histamine H1-receptor antagonists (alcoholamines: diphenhydramine, carbinoxamine, and clemastine; ethylenediamines: mepyramine, tripelennamine, and clemizole; alkylamines: triprolidine and chlorpheniramine; piperazines: meclizine and homochlorcyclizine; phenothiazines: promethazine) on neuronal uptake of dopamine (DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), the effects on the turnover of these monoamines were examined in the mouse brain, based on the alpha-methyl-p-tyrosine-induced depletion of DA and NA or probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The DA turnover was reduced remarkably by diphenhydramine, tripelennamine, and promethazine, and also significantly by chlorpheniramine, mepyramine, clemizole, and homochlorcyclizine, at doses used in the ordinary animal experiments. The 5-HT turnover was reduced markedly by mepyramine, tripelennamine, and chlorpheniramine. In contrast, the NA turnover was increased by promethazine and homochlorcyclizine, possibly due to their antagonistic effects on alpha-adrenoceptors. These results suggest that (1) the degree of inhibition of the uptake of DA and 5-HT by histamine H1-receptor antagonists is considerably different, (2) most H1-antagonists have little influence on NA uptake and some compounds enhance NA release, and that (3) carbinoxamine, clemastine, triprolidine, and meclizine have comparatively weak influences on monoamine metabolism. These effects on brain monoamine systems may be related to some central actions of histamine H1-receptor antagonists, such as an addiction to these compounds combined with opioids.

Animals↗

PubMed1994

Characteristics of tail-tremor induced by nicotine in rats.

To characterize the tail-tremor and locomotor hyperactivity induced by repeated nicotine administration, the effects of nicotinic, alpha-adrenergic and dopaminergic blockers were investigated in rats. Daily administration of nicotine (0.5 mg/kg, s.c.) induced tail-tremor from the 4th day, which became more marked in intensity by subsequent administration. Locomotor hyperactivity was also induced by nicotine, which was enhanced by daily administration. The tail-tremor and locomotor hyperactivity induced by repeated nicotine administration were inhibited by mecamylamine (0.1-1 mg/kg, i.p.) but not by hexamethonium (0.5 and 1 mg/kg, i.p.). Clonidine (0.02 and 0.04 mg/kg, i.p.) and prazosin (0.5 and 1 mg/kg, i.p.) reduced tail-tremor more markedly than hyperactivity. However, haloperidol (0.05-0.2 mg/kg, i.p.) and chlorpromazine (1-5 mg/kg, i.p.) reduced hyperactivity more markedly than tail-tremor. These results suggest that nicotine-induced tail-tremor and hyperactivity are due to an increased susceptibility of central nicotinic receptors of nicotine followed by catecholaminergic mechanisms, and that tail-tremor may be more associated with the noradrenergic system than the dopaminergic system.

Animals↗

PubMed1994

Increase in the extracellular histamine concentration in the rat striatum by mu-opioid receptor activation.

The effects of morphine and selective ligands for mu-, kappa-, and delta-opioid receptors on the extracellular histamine (HA) concentration in the striatum of freely moving rats were examined by in vivo microdialysis. On the day after implantation of the dialysis probe, the HA output per 30-min period was measured using HPLC-fluorometry. Morphine (3.8 mg/kg, s.c.) significantly increased the HA output by approximately 200% 1-3 h after treatment. This effect was completely antagonized by naltrexone (1.6 mg/kg, s.c.). The HA output decreased to a level below 10% of the basal value by 4 h after treatment with (S)-alpha-fluoromethyl-histidine (77 mg/kg, s.c.). In such animals, morphine (3.8 mg/kg, s.c.) had no influence on the HA output. [D-Ala2,MePhe4,Gly(ol)5]Enkephalin (DAGO; 0.2 microgram, i.c.v.), a selective mu-agonist, significantly increased the HA output by approximately 150% 0.5-1.5 h after treatment, and this effect was also completely blocked by naltrexone. A selective kappa-agonist, U-50,488 (3.8 and 7.6 mg/kg, s.c.), and a selective delta-agonist, [D-Pen2,D-Pen5]enkephalin (0.5 and 2 micrograms, i.c.v.), had no effect on the HA output. These findings suggest that the stimulation of mu-opioid receptors by morphine and DAGO increases the extracellular HA concentration by accelerating HA release from nerve endings.

Animals↗

PubMed1994

Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

Animals↗

PubMed1994

Effect of acute and chronic immobilization stress on plasma levels of nicorandil administered orally to rats.

Effects of acute (15h) and chronic (15h x 7 days) immobilization (IM) stress on plasma levels of nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate (ester)] administered orally were examined in rats. The maximum plasma level was reached 30 min after administration. Acute IM stress significantly reduced plasma nicorandil levels both in the absorption and elimination phases (15 min and 2-6h after administration, respectively). Chronic IM stress further intensified the reduction of nicorandil levels in the absorption phase, but attenuated the influence of acute stress in the elimination phase. No significant difference was observed one day after removal of chronic IM stress. These results suggest that chronic IM stress markedly inhibits the absorption of nicorandil, but the distribution, metabolism and excretion were influenced more by acute IM stress.

Acute Disease↗

PubMed1993

N alpha-methylhistamine inhibits intestinal transit in mice by central histamine H1 receptor activation.

The effects of (R)alpha-methylhistamine and N alpha-methylhistamine on intestinal transit were examined in mice. The passage of a charcoal meal in the gastrointestinal tract was dose dependently inhibited by N alpha-methylhistamine (1-20 mg/kg i.p.), but not by a selective H3 receptor agonist (R)alpha-methyl-histamine (1-50 mg/kg i.p.). The inhibitory effect of N alpha-methylhistamine (20 mg/kg) was attenuated by pretreatment with H1 receptor antagonists (mepyramine 5 mg/kg i.p. or 5 micrograms i.c.v. and triprolidine 5 mg/kg i.p.), but not by cimetidine (10 mg/kg i.p.), zolantidine (5 mg/kg i.p.), a brain-penetrating H2 receptor antagonist, or thioperamide (5 mg/kg i.p.), a selective H3 receptor antagonist. The effect of N alpha-methylhistamine was also attenuated by combined treatment with phentolamine and propranolol (5 and 15 mg/kg s.c., respectively) and by pretreatment with 6-hydroxydopamine (20 mg/kg i.p., 2 days before). N alpha-Methylhistamine markedly decreased histamine turnover in the mouse brain. These findings suggest that intestinal transit is inhibited by N alpha-methylhistamine via stimulation of central H1 but not H3 receptors and that stimulation of the sympathetic system is involved in this effect.

Animals↗

PubMed1993

Aggravation of ischemic neuronal damage in the rat hippocampus by impairment of histaminergic neurotransmission.

Delayed damage to hippocampal CA1 pyramidal cells was observed in rats subjected to cerebral ischemia caused by 10 min of 4-vessel occlusion. Animals pretreated with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, showed significantly more necrotic cells than did control animals. Mepyramine (H1-antagonist) and (R) alpha-methylhistamine (H3-agonist), but not zolantidine (H2-antagonist), significantly aggravated the delayed neuronal death. These results suggest that histaminergic neurons have a protective role, probably via H1-receptors, in the development of delayed neuronal death caused by cerebral ischemia.

Animals↗

PubMed1993

Possible explanations for the antagonism by nicotine against reserpine-induced depletion of monoamines in mouse brain.

The inhibitory effect of nicotine pretreatment on reserpine-induced depletion of monoamines in mouse brain was investigated. The depletion of brain monoamines by 24 h after intraperitoneal injection of reserpine (2 mg/kg) was dose-dependently inhibited by nicotine (0.3-10 mg/kg, s.c.) pretreatment 20 min before reserpine injection. This effect of nicotine was more marked on dopamine depletion than on noradrenaline or 5-hydroxytryptamine depletion. The nicotine pretreatment also inhibited the reserpine-induced hypothermia and decrease in the locomotor activity. When reserpine (2 mg/kg) was injected intraperitoneally, the inhibitory effect of nicotine (3 mg/kg, s.c.) on the reserpine-induced depletion of brain monoamines and heart noradrenaline was not antagonized by hexamethonium (8 mg/kg, s.c.) but rather potentiated by mecamylamine (2 mg/kg, s.c.). However, when reserpine (0.5 mg/kg) was injected intravenously, pretreatment with nicotine (3 mg/kg, s.c.) inhibited the reserpine-induced dopamine depletion only, and this effect of nicotine was completely blocked by mecamylamine but not by hexamethonium. These results suggest that inhibitory effect of nicotine on the intraperitoneal reserpine-induced depletion of brain monoamines is due to an inhibition of absorption of reserpine, and that central nicotinic action is also involved in the antagonism by nicotine of reserpine-induced dopamine depletion.

Animals↗

PubMed1993

Effect of a new psychoactive compound, MCI-225, on brain monoamine metabolism in rats.

Effect of MCI-225 on brain monoamine metabolism was examined in rats. MCI-225 (30 mg/kg, p.o.) had no influence on noradrenaline (NA) levels, but significantly inhibited the NA turnover in the hippocampus and hypothalamus. This compound also significantly increased the 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine ratio in the cerebral cortex, hippocampus and striatum; and it enhanced the probenecid-induced 5-HIAA accumulation in the striatum. In the microdialysis study, MCI-225 markedly increased the NA output, but decreased the 3,4-dihydroxyphenylethyleneglycol output from the hypothalamus of urethane-anesthetized rats. These results suggest that MCI-225 enhances both noradrenergic and serotonergic function by inhibiting NA uptake and accelerating 5-HT turnover, respectively.

Animals↗

PubMed1993

Microdialysis study of the effects of sedative drugs on extracellular histamine in the striatum of freely moving rats.

The effects of some sedative drugs on the extracellular concentration of histamine (HA) in the striatum of conscious freely moving rats were examined by in vivo microdialysis coupled with high-performance liquid chromatography-fluorometry. The HA output did not significantly change until 4 hr after intraperitoneal saline injection. Pentobarbital (46 mg/kg i.p.) significantly decreased the HA output by 76% at 0.5 to 1 hr after treatment. Muscimol (5 mg/kg i.p.) and diazepam (20 mg/kg i.p.) also significantly decreased the HA output at 0.5 to 1.5 hr after treatment. delta 9-Tetrahydrocannabinol (5 mg/kg i.p.) induced biphasic changes in the HA output, i.e., a significant increase and a significant decrease were observed at 0 to 0.5 hr and 1.5 to 2.5 hr after treatment, respectively. Reserpine (5 mg/kg i.p.) significantly increased the HA output by 47% to 58% at 0 to 2 hr after treatment. The HA output decreased to a level below 10% of the basal value by 4 hr after treatment with (S)-alpha-fluoromethylhistidine (77 mg/kg i.p.). Reserpine slightly restored the HA output (to about 25% of the original basal value). These results, taken together with our previous results, suggest the following: 1) pentobarbital, muscimol and diazepam inhibit HA release; 2) tetrahydrocannabinol initially increases HA release for a short period but markedly decreases the release thereafter; and 3) reserpine increases the extracellular HA concentration probably as a result of inhibition of its elimination.

Animals↗

PubMed1992

GAP-43 gene expression is increased in anterior horn cells of amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), neuronal loss and axonal degeneration occur in motor neurons. Although there is limited axonal regeneration, surviving motor neurons send collateral sprouts to denervated muscle fibers. GAP-43, a protein enriched in growth cones and synaptic terminals, is thought to have a role in axonal elongation and synaptogenesis. GAP-43 messenger RNA (mRNA) expression was evaluated in ALS spinal cords using Northern blot analysis and in situ hybridization to assess whether surviving neurons can mount an appropriate response to injury. There was a two- to four-fold increase in GAP-43 mRNA in ALS that localized to the anterior horn cells. The increase in GAP-43 mRNA indicates that the mechanism which leads to degeneration in ALS does not compromise the neuron's capacity for vigorous expression of growth-associated proteins.

Amyotrophic Lateral Sclerosis↗

PubMed1992

Inhibition of histamine turnover by 8-OH-DPAT, buspirone and 5-hydroxytryptophan in the mouse and rat brain.

The effects of 5-hydroxytryptamine (5-HT) receptor agonists on histamine turnover in mouse and rat brains were examined. The histamine turnover rate was estimated from the accumulation of tele-methylhistamine 90 min after i.p. injection of pargyline (65 mg/kg). In whole mouse brains, the histamine turnover was significantly inhibited by the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (greater than 0.5 mg/kg) and buspirone (greater than 2 mg/kg) injected s.c. 10 min before pargyline treatment. 5-hydroxytryptophan (20 mg/kg) also significantly inhibited histamine turnover. Injections of the 5-HT1B agonist m-trifluoromethylphenylpiperazine (10 and 20 mg/kg) or the 5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1, 2 and 5 mg/kg), however, did not affect histamine turnover. The inhibitory effect of 8-OH-DPAT (1 mg/kg) on histamine turnover was significantly antagonized (by 40%) by pindolol (20 mg/kg) and slightly antagonized (by 29%) by spiperone (10 mg/kg), while methysergide (20 mg/kg) and ketanserin (10 mg/kg) demonstrated no antagonistic effects. 8-OH-DPAT (0.3 and 1 mg/kg) also showed an inhibiting effect on histamine turnover in various regions of rat brains. Although the extent of inhibition was slightly larger in the striatum and cerebral cortex, there was no marked regional difference. These results suggest that histaminergic activity in the brain is regulated by 5-HT1A receptors.

5-Hydroxytryptophan↗