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T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 433 records · Page 24Linked to original sources
PubMed1977

[Effects of difenamizole on behavior maintained by schedule of positive reinforcement (author's transl)].

The anti-nociceptive dose of difenamizole, morphine, aminopyrine and aspirin was studied for effects on behavior maintained by schedule of positive reinforcement. Male, albino rats were trained to press a lever for food pellets on a fixed-ratio (FR) 10 and 30 schedule of reinforcement or a differential reinforcement of low rates of responding (DRL) schedule. Difenamizole (200 and 400 mg/kg, p.o.) produced a dose-related decrease in the response under FR-10 schedule. The response rate decrease observed under the FR-10 schedule was similar to that resulting from the oral administration of 400 mg/kg of aminopyrine. Response in the FR-30 schedule was not affected by any dose of difenamizole (100 approximately 400 mg/kg, p.o.) and aminopyrine (200 approximately 400 mg/kg, p.o.). In the response maintained by the DRL schedule, the overall response rate and the mean interresponse time were not altered significantly by most doses of difenamizole, aminopyrine and aspirin given, however, food reinforcement was decreased significantly with ingestion of these drugs. Morphine (20 mg/kg, p.o.) shortened the mean interresponse time and increased the response in DRL schedule. These results suggest that the central action of difenamizole is similar to that produced by aminopyrine, but not that produced by morphine.

Aminopyrine↗
PubMed1976

Dffects of imipramine on auditory sensitivity in the rat in relation to initial sensitivity.

Rats were divided into 2 groups according to their absolute auditory thresholds, as measured by a psychophysical method of limits using an operant conditioning technique. The procedure required a water-deprived rat to bar press repeatedly until a 3 s pure tone (3 kHz) came on. VR-15 schedule was used to determined the frequency of occurrence of the tone. Only within 4 s after the tone onset could the rat get water reinforcement by sticking its nose into the dipper area. The descending method was used with tone intensities ranging from 120 to 40 dB, in 2 dB steps. Imipramine was then administered 3 times at 24-h intervals (40, 80 and 160 mg/kg, p.o., respectively), and each rat was tested at 4, 8, and 12 h after each administration. Rats with high initial thresholds showed a decrease in thresholds with the lower dose of imipramine, and those with low initial thresholds an increase with the higher dose. An analysis of variance of these data showed significant effects of the type of subject (in terms of the level of initial thresholds), dose and interval conditions, and their interaction. It was demonstrated that the lower the initial sensitivity the greater the increase in sensitivity by imipramine.

Animals↗
PubMed1976

[Relationship between biogenic amines and analgesic action of difenamizole in heat induced reflexes].

Effects of drugs that modify catecholaminergic or tryptaminergic mechanisms were determined in experimental animals regarding the analgesic action of difenamizole, morphine, and aminopyrine. Analgesia was assessed by the hot plate method in mice and the hot water induced tail withdrawal reflex in rats. Both 5-hydroxytryptophan (5-HTP) and L-dopa potentiated the analgesic action of morphine, but antagonized the action of difenamizole in the hot plate test. p-Chlorophenylalanine (pCPA), alpha-methyl-p-tyrosine (alpha-MT), and reserpine antagonized the effect of morphine as assessed by this same test. alpha-MT potentiated the analgesic action of difenamizole. The analgesic action of aminopyrine was hardly modified in the hot plate method by pretreatment with 5-HTP, pCPA, L-dopa, and alpha-MT. In rats, 5-HTP antagonized the effect of morphine, while pCPA, L-dopa, and alpha-MT caused no appreciable change in the analgesic action of morphine in the hot water induced tail withdrawal reflex. The effect of difenamizole was not modified by pretreatment with these monoamine-related drugs. On the other hand, brain 5-hydroxytryptamine content was increased by pretreatment with 5-HTP in both tests. These results suggest that the analgesic action of difenamizole and morphine, as measured in the hot plate test in mice, may be mediated by catecholamines and 5-hydroxytryptamine, but that other mechanisms may be involved in the hot water induced tail withdrawal relfex in rats. In addition, the biogenic amines may play a different role depending on the type of analgesic.

5-Hydroxytryptophan↗
PubMedDate not supplied

Possible involvement of nitric oxide in quinolinic acid-induced convulsion in mice.

Quinolinic acid (QA) induced clonic and tonic convulsions in mice when it was injected into the cerebral ventricle. Pretreatment with L-arginine (L-Arg), a substrate of nitric oxide (NO) synthase (NOS), and/or 5,6,7,8-tetrahydrobiopterin (THB), cofactor of NOS, tended to potentiate QA-induced convulsion. NG-monomethyl-L-arginine (NMMA), a competitive NOS inhibitor, diminished QA-induced convulsion. This effect of NMMA was attenuated by coadministration of L-Arg or THB. Sodium nitroprusside (SNP), which spontaneously releases NO, did not potentiate, but diminished QA-induced convulsion. These findings suggest that an endogenous NO may be involved, at least in part, in QA-induced convulsion in mice, and that an exogenous NO released from SNP may cause downregulation of N-methyl-D-aspartate (NMDA) receptor activity, and thereby prevent the excessive excitation of NMDA receptors and subsequent convulsion caused by QA.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Endorphins do not affect behavioral stress responses in mice.

Effects of endorphins on behavioral stress responses were investigated in mice. For this purpose, we used environment-induced conditioned suppression of motility and forced swimming-induced immobility. The cerebral ventricular administration of alpha-endorphin (2.5-10 nmol), beta-endorphin (0.38-1.5 nmol), or gamma-endorphin (2.5-10 nmol) failed to affect either the environment-induced conditioned suppression of motility or the forced swimming-induced immobility. We have indicated previously that enkephalins attenuate both stress responses and, in contrast, dynorphin potentiates them. These findings indicate that the endorphinergic systems are not responsible for behavioral stress responses and that the role played by endorphins in the present stressful situations may be different from that of enkephalin and dynorphin.

Animals↗
PubMedDate not supplied

Phencyclidine-induced expression of c-Fos-like immunoreactivity in mouse brain regions.

For the purpose of studying a role of immediate early genes in psychotomimetic-induced behavioral excitation, we experimentally enhanced the locomotor activity of mice by acute administration of phencyclidine and examined the expression and localization of the c-Fos-like and c-Jun-like immunoreactivities in brain regions. A single injection of phencyclidine (5.0 mg/kg, i.p.) significantly increased not only the locomotor activity but also the expression of c-Fos-like immunoreactivity in several brain regions, particularly in the parietal cortex, hippocampal dentate gyrus, piriform cortex and hypothalamus. Interestingly, the c-Fos-like immunoreactivity in the parietal cortex continued to increase for 1 week after the phencyclidine injection. These results indicate that phencyclidine, even injected only once, can induce the persistent expression of c-Fos or c-Fos-related protein(s) in the mouse brain, and also suggest the possibility that such a c-Fos expression may underlie the behavioral and/or psychotomimetic effects of phencyclidine.

Analysis of Variance↗
PubMedDate not supplied

Longitudinal study of spinal deformity in Duchenne muscular dystrophy.

To investigate the natural course of the spinal deformity in Duchenne muscular dystrophy (DMD) and its clinical relevance, longitudinal series of spinal radiographs and medical records of 46 patients with DMD were reviewed. The natural course of the deformity was classified into three types; type 1 (n = 21), unremittent progression of scoliosis with kyphosis; type 2 (n = 18), transition from kyphosis to lordosis before age 15 years; and type 3 (n = 7), less deformity without prominent longitudinal changes. Age at loss of ambulatory ability was not a predictor of type. Neither was the age at which the Cobb angle was 30 degrees correlated with the rate of subsequent progression. Because the spinal deformity always progresses, we consider spinal surgery justifiable in type 1, when a certain strict indication exists, such as spinal deformity > 30 degrees and age < 15 years in patients with > 35% predicted value of vital capacity. In type 2, operation may be necessary in patients in whom Cobb angle will progress unremittently. There is no surgical indication for patients with type 3.

Adolescent↗
PubMedDate not supplied

Inhibitory effect of erythromycin on P-glycoprotein-mediated biliary excretion of doxorubicin in rats.

The macrolide antibiotic erythromycin has recently been shown to overcome the resistance to anticancer drugs that results from overexpression of P-glycoprotein. The present study, using erythromycin lactobionic acid as a model drug, investigated the inhibitory effects of erythromycin on the efflux of doxorubicin from P388/ADR cells expressing P-glycoprotein and on the biliary excretion mechanism of doxorubicin in rats, which is primarily mediated by P-glycoprotein. Erythromycin lactobionic acid was found to inhibit the efflux of doxorubicin (5 microM) from P388/ADR cells in a concentration-dependent manner. In rats receiving constant-rate infusion of doxorubicin (30 micrograms/min), both the biliary and renal clearance of this drug dramatically decreased and its plasma concentrations increased after an intravenous injection of erythromycin lactobionic acid (100 mg/kg as erythromycin). These results suggest that erythromycin competitively inhibits P-glycoprotein-mediated biliary and renal excretion of doxorubicin. The effect of erythromycin on the biliary secretion of doxorubicin was also analyzed quantitatively by the competitive inhibition model. The computer-estimated values of Vmax/Km, Km and Ki were 8.79 ml/minute, 0.82 microgram/ml and 0.41 microgram/ml, respectively. The findings of these experiments suggest that the inhibitory effect of erythromycin on the P-glycoprotein-mediated biliary excretion of doxorubicin is competitive and that combination chemotherapy of doxorubicin with erythromycin may induce toxicity as a result of increased plasma concentrations of doxorubicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Pharmacokinetics and renal handling of enprofylline in pregnant rats.

The pharmacokinetics and renal handling of enprofylline during pregnancy were investigated in Sprague-Dawley rats. Significant differences in the pharmacokinetic parameters of enprofylline were observed between nonpregnant rats and pregnant rats on the 20th day of gestation: volume of distribution was higher, and systemic clearance was lower in pregnant rats. Parameters obtained from rats at 7 days postpartum were the same as those obtained from nonpregnant rats. There were no significant differences in the fraction of urinary excretion of enprofylline between nonpregnant and pregnant rats. The protein binding of enprofylline in the plasma of pregnant rats was significantly lower than in nonpregnant rats, as a decrease in the albumin concentration consequentially reduced the binding capacity of enprofylline. The volume of distribution for unbound enprofylline in pregnant rats was not significantly different from nonpregnant rats, although a significant decrease was observed in pregnant rats in the systemic clearance for unbound enprofylline. In addition, the clearance ratio was lower in pregnant rats (2.8) when compared with nonpregnant rats (6.4). Pregnancy caused a decrease in the apparent maximum capacity of transport (Vmax) from 29.9 to 20.8 micrograms/min and in the Michaelis-Menten constant (KM) from 2.59 to 2.26 micrograms/ml, indicating that the tubular secretion ability of enprofylline becomes reduced during pregnancy. These results suggest that changes that occur in the plasma protein binding behavior and in renal handling as a result of pregnancy are primary factors influencing the disposition of enprofylline during pregnancy.

Animals↗
PubMedDate not supplied

The interaction between the cholinergic and dopaminergic system in learning and memory process in rats.

In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating role on both short-term and long-term memory tested by Y-maze task and multi-trial passive avoidance test, respectively, since scopolamine, a specific mAChRs antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w., i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist, administered once caused a significant facilitating effect on short-term memory. A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days had about the same facilitating effect on short- and long-term memory without affecting information acquisition. In rats, having mAChRs and nAChRs blocked by means of scopolamine and chlorisondamine respectively, a low dose of nicotine administered once caused a significant improvement of long-term memory deficits without affecting significantly short-term memory. A higher dose of nicotine administered 5 consecutive days in rats with a double blockade of cholinergic receptors had the same ameliorating effect on long-term memory deficits as low dose. Our data suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.

Animals↗
PubMedDate not supplied

Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats.

Mutant rats possessing conjugated hyperbilirubinemia have recently been established from Sprague-Dawley rats (SDRs) and are called Eisai hyperbilirubinemic rats (EHBRs). The effects of hyperbilirubinemia on the disposition, renal handling, and protein binding behavior of enprofylline, which is mainly excreted into the urine by an active tubular secretion mechanism, were investigated in 9- and 19-week-old EHBRs and compared with their age-matched normal SDRs. Enprofylline was administered intravenously at a dose of 2.5 mg/kg, which exhibits linear kinetics. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model-independent methods. Both systemic clearance and volume of distribution at steady state of enprofylline significantly increased in 19-week-old EHBRs. However, there were no differences in the glomerular filtration rate estimated as inulin clearance and fraction of urinary excretion as unchanged drug between EHBRs and normal SDRs. Significant decreases in both the binding capacity and number of binding sites were observed in 19-week-old EHBRs, but no such changes were observed between 9-week-old EHBRs and SDRs. Hyperbilirubinemia in EHBRs had no effect on the pharmacokinetics and renal handling of unbound enprofylline. These results indicate that the pharmacokinetics of enprofylline, but not renal handling, glomerular filtration, or tubular secretion are modified in EHBRs by changes in protein binding behavior.

Animals↗