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Biomedical subjects

N Motohashi

Publications and source records attributed to N Motohashi.

At least 73 records · Page 4Linked to original sources

Possible mechanism of dantrolene stabilization of cultured neuroblastoma cell plasma membranes.

Some reports have suggested that dantrolene interacts directly with the membrane bilayer. We investigated effects of dantrolene on changes in membrane properties induced by compound 48/80 (C48/80), a membrane stimulator. The addition of C48/80 for 1 min elicited a rapid, dose-dependent Ca2+ influx, which was reduced to 14% by the absence of external Ca2+. Dantrolene inhibited the C48/80-induced increase in Ca2+ permeability of plasma membranes in a concentration-dependent manner (0.33-10 microM, IC50 value was 5 microM). We next examined C48/80-induced changes in structural and dynamic membrane properties by electron spin resonance (ESR). The ratio h0/h-1 was determined to evaluate membrane fluidity. C48/80 increased the membrane fluidity in a concentration-dependent manner (0.1-0.56 mg/ml). Dantrolene (10 microM) itself did not change the membrane fluidity, but it significantly reduced the C48/80-induced increase in membrane fluidity (0.56 mg/ml). Moreover, the C48/80-induced increase in fluidity was dependent on extracellular Ca2+. We conclude that dantrolene protects neuroblastoma cell plasma membrane from C48/80-induced membrane perturbation, which causes Ca2+ influx and an increase in membrane fluidity. These findings strongly suggest that dantrolene directly stabilizes the neuronal plasma membrane.

Animals↗

Increase in serotonin 1A receptors in the dentate gyrus as revealed by autoradiographic analysis following repeated electroconvulsive shock but not imipramine treatment.

The effects of repeated treatment with electroconvulsive shock (ECS) and imipramine on [3H]8-OH-DPAT binding to serotonin1A (5-HT1A) receptors in the rat brain were studied by quantitative autoradiographic analysis. A large number of binding sites for [3H]8-OH-DPAT were observed in the hippocampus, especially the dentate gyrus, CA1+CA2 field, dorsal raphe nucleus and septum. Repeated treatment with ECS, but not repeated imipramine treatment, significantly increased [3H]8-OH-DPAT binding sites in the dentate gyrus. These results suggest that the increase in [3H]8-OH-DPAT binding sites in the dentate gyrus may be important in ECS therapy for depressive illness.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

P-A cephalometric analysis of nonoperated adult cleft lip and palate.

P-A cephalometric analysis was performed on the craniofacial morphology in 88 Brazilian men with nonoperated and operated cleft lip and palate. For the comparative study, these subjects were divided into the following four groups: (1) 31 nonoperated unilateral cleft lip and palate (UCLP), (2) 24 nonoperated bilateral cleft lip and palate (BCLP), (3) 16 operated UCLP, (4) 17 operated BCLP. Thirty Brazilian men without cleft lip and palate were used as control subjects. In comparison with the control subjects, nonoperated BCLP and UCLP showed remarkable facial deformity characterized by increased width of various facial parts. Facial morphology of surgically treated BCLP and UCLP, however, was very similar to that of noncleft subjects, apart from the immediate cleft region. There was no remarkable difference in the facial morphology between nonoperated BCLP and UCLP, except for the cleft width and the deviation of nasal septum base, while the only significant difference between operated BCLP and UCLP was in the cleft width.

Adolescent↗

TJS-010, a new prescription of Kampo medicine with putative antidepressive and anxiolytic properties.--A behavioral study using experimental models for depression and anxiety.

We investigated the effect of TJS-010, a new prescription of Kampo or oriental medicine, on the locomotor activity and body temperature in rats in order to determine its antidepressive and anxiolytic effects. Tetrabenazine(TBZ), which sometimes induces depression in humans, decreased the spontaneous locomotion in rats, and attenuated the content of amines in several regions in the rat brain when intraperitoneally injected. TJS-010 was orally administered at a concentration of 750 mg/kg, and inhibited the locomotor suppression. The content of amines was not, however, altered. These results indicate that TJS-010 postsynaptically modulates the transmission or transduction. Imipramine, 5mg/kg, also enhanced locomotion in TBZ-treated rats, which was similar to the effect of TJS-010. These results suggest that TJS-010 has an antidepressive effect. TJS-010 also facilitated the hypothermia induced by subcutaneous injection of 0.1 mg/kg (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), which is known to be mediated by serotonin-1A receptors. The hypothermia in the rats via an activation of serotonin-1A receptors is often observed with anxiolytic drugs. These results may raise the possibility that TJS-010 has an anxiolytic property. TJS-010 may serve as a useful drug for the treatment of those who suffer from depressive and anxiety disorders.

Administration, Oral↗

[Studies on lithium potentiation of antidepressant treatment].

The effects of chronic administration of clomipramine or citalopram (CMI or CIT, 20 mg/kg i.p. daily for 19 days) with/without short-term administration of lithium (Li, 2 mEq/kg i.p. daily for 5 days) on the concentration of monoamines and their metabolites and serotonergic receptors were studied in the rat cerebral cortex. Li or CMI by itself had no effects on the concentration of monoamines and their metabolites, but a combination of CMI and Li increased that of 5-HIAA. CIT alone increased that of 5-HIAA, and a combination of CIT and Li increased that of 5-HIAA more than CIT alone. There were no changes in 5-HT or 5-HIAA after acute administration of CMI or CIT with/without Li. For the serotonergic receptors, [3H] 8-OH-DPAT and [3H] paroxetine binding did not change in any of the treatments. CMI alone or a combination of CMI and Li reduced [3H] ketanserin binding, but Li did not potentiate this effect. It is speculated that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the activation of presynaptic serotonergic system.

Animals↗

Acute swim stress increases benzodiazepine receptors, but not GABAA or GABAB receptors, in the rat cerebral cortex.

We have examined the effects of swim stress on gamma-aminobutyric acidA (GABAA), GABAB and benzodiazepine (BZD) receptors in synaptic membranes from rat brain. Acute, but not repeated, stress increased the number of BZD receptors in the cerebral cortex. The stress manipulation did not change BZD receptors either in the hippocampus or cerebellum. Furthermore, both GABAA and GABAB receptors did not change in the cerebral cortex, hippocampus or cerebellum after acute and repeated stress. GABA-stimulated BZD binding was not changed following acute or repeated stress. These results suggest that cortical BZD receptors are closely related to responses to acute stress.

Animals↗

Quantitative evaluation of the shape and the elasticity of repaired cleft lip.

Tight lip in repaired cleft lip patients with or without cleft palate (CL[P]) has been discussed as one of the causal factors of maxillary growth retardation and malocclusion. The purpose of this study was to evaluate the shape and the elasticity of repaired cleft lip quantitatively. Forty-one Japanese CL(P) patients were examined. Fifty-four noncleft patients under orthodontic treatment were used as a control group. An apparatus to stretch the anguli oris bilaterally was devised and the extensibility of the lip was measured to evaluate lip elasticity. Standardized photos of the lips were taken to examine lip shape. CL(P) patients showed poor elasticity of the lip. This trend was more apparent in bilateral CL(P) patients than in unilateral CL(P) patients. The upper lip of CL(P) patients was significantly shorter in vertical height. These results clearly demonstrated the tightness and shortness of the repaired lip in CL(P) patients.

Adolescent↗

[Effects of risperidone on catalepsy and cerebral dopamine, serotonin and GABA metabolism in the rat: comparison with haloperidol].

Effects of risperidone (RIS, 1 mg/kg) and haloperidol (HPD, 1 mg/kg) on catalepsy, and monoamine and GABA metabolism were examined in the rats. Catalepsy was evaluated by means of a horizontal bar method. The rats were sacrificed 3 h after orally administered HPD or RIS. Levels of monoamines and their metabolites determined by HPLC-ECD, and GABA levels were determined by a radioreceptor assay. The score of catalepsy was significantly low 120 min after administration of RIS as compared to HPD. In comparison to control, HPD treatment significantly increased DOPAC in the frontal cortex, thalamus + hypothalamus, and striatum, and HVA in the striatum. In RIS-treated rats, DOPAC and HVA were significantly increased in the striatum. Moreover, RIS increased 5-HIAA in the frontal cortex, hippocampus, thalamus + hypothalamus, mid brain, pons and striatum. The concentration of GABA was unchanged in all areas of the brain after treatment with HPD, but was significantly decreased in the pons in RIS-treated rats. The present results suggested that the effects of RIS on serotonin and GABA metabolism may be related to the cause of the low potency of RIS to induce catalepsy.

Animals↗

GABA receptor alterations after chronic lithium administration. Comparison with carbamazepine and sodium valproate.

1. Effects of lithium, carbamazepine, sodium valproate and baclofen on GABA receptors were examined in several regions of the rat brain. 2. [3H]Muscimol (MUS) and [3H] (-)baclofen (BAC) were used to label GABAA and GABAB receptors, respectively, in synaptic membranes from rat brain. 3. Single treatment with lithium chloride, carbamazepine or sodium valproate did not change [3H]MUS or [3H]BAC binding in the frontal cortex, hippocampus and thalamus. 4. Following chronic treatment with lithium, carbamazepine or sodium valproate, [3H]BAC binding was significantly increased in the hippocampus but not in the frontal cortex, thalamus or striatum. 5. [3H]Muscimol binding did not change in any region examined after chronic treatment with lithium, carbamazepine or sodium valproate. 6. Single and chronic administration of baclofen did not change [3H]MUS or [3H]BAC binding. 7. One common mechanism of action of mood stabilizers may be mediated by GABAB receptors in the hippocampus.

Animals↗

Effects of sulpiride and oxypertine on the dopaminergic system in the rat striatum.

We have examined the effects of sulpiride, oxypertine and haloperidol on the behavioral and biochemical dopamine receptor function in the rat striatum. Although acute treatment with haloperidol or oxypertine induced catalepsy, tolerance to catalepsy developed following chronic treatment with haloperidol but not with oxypertine. Rats treated with acute or chronic sulpiride did not show signs of catalepsy. Intracerebroventricular administration of sulpiride, however, induced catalepsy and tolerance developed after chronic treatment. After chronic treatment with either of these three drugs, dopamine D2 receptors were up-regulated in the striatum. While acute administration of haloperidol, sulpiride or oxypertine increased the concentration of homovanillic acid in the striatum, the rate of increases was attenuated following chronic treatment with haloperidol or sulpiride, but not with oxypertine. While acute administration of sulpiride or oxypertine decreased dopamine, the decrease was attenuated following repeated administration of sulpiride but not of oxypertine. These results suggest that the unique pharmacological profile of oxypertine may be related to its therapeutic effect of activating apathetic patients, and that both sulpiride and oxypertine may cause tardive dyskinesia, as haloperidol does.

Animals↗

Inhibitory effects of hyaluronan on [14C]arachidonic acid release from labeled human synovial fibroblasts.

The effects of hyaluronan (HA) on the release of arachidonic acid (AA) from phospholipids induced by bradykinin in synovial fibroblasts of osteoarthritic patients were examined. HA inhibited [14C]AA release from prelabeled synovial cells stimulated with and without bradykinin 1 hr after incubation with HA and thereafter. The inhibitory effects of HA on [14C]AA release were dependent on the concentration and molecular weight of HA. However, inhibition of [14C]AA release by HA was not merely due to the viscosity of HA. The [14C]AA release induced by calcium-ionophore A23187 was also inhibited by HA with a high molecular weight. In addition, HA did not affect [14C]AA uptake by the cells. Our results suggest that HA with a high molecular weight elicits anti-inflammatory effects, at least in part, by inhibiting AA release in inflamed joints.

Arachidonic Acid↗

[A case of Nasu-Hakola's disease with T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen].

A 30-year-old female received a head injury at the age of 22 years. Subsequently neurological and psychiatric symptoms, such as personality change, urinary incontinence, dementia and gait disturbance developed. On admission, her cognitive function was severely impaired. Brain CT disclosed cerebral atrophy, dilatation of the lateral ventricle and calcification of the basal ganglia. Pathologically membranous structures were recognized in bone marrow. On the basis of these clinical findings, a diagnosis of Nasu-Hakola's disease was made. In this case, a T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen was characteristic. This finding may be related to intracranial calcification.

Adult↗