Biomedical subjects

M Hiramatsu

Publications and source records attributed to M Hiramatsu.

At least 19 recordsLinked to original sources

PubMed1995

Effects of dynorphin A-(1-13) on carbon monoxide-induced delayed amnesia in mice studied in a step-down type passive avoidance task.

The effects of dynorphin A-(1-13) on carbon monoxide (CO)-induced amnesia in mice were investigated using a step-down type passive avoidance task. Memory deficiency occurred in mice when training commenced 7 days after CO exposure although it was not produced 1 day after CO exposure. The median step-down latency in the retention test of the CO-exposed group was significantly shorter than that of the control group. Administration of dynorphin A-(1-13) (1.5 nmol/mouse i.c.v.) 15 min before the first training session prolonged the step-down latency in the CO-exposed group. Dynorphin A-(1-13) administered immediately after the first training session or administered 15 min before the retention test also prolonged the step-down latency in the CO-exposed group. To determine whether this effect of dynorphin A-(1-13) was mediated via kappa-opioid receptors, we attempted to block its action using a kappa-opioid receptor antagonist (nor-binaltorphimine). Nor-binaltorphimine (5.44 nmol/mouse i.c.v.) blocked the effect of dynorphin A-(1-13) on delayed amnesia. However, dynorphin A-(1-13) (0.5, 1.5 and 5.0 nmol/mouse) did not facilitate the acquisition of memory in normal mice. These results suggest that dynorphin A-(1-13) modulates the kappa-opioid receptor-mediated opioid neuronal system, and that it ameliorates the disruptive effect of CO on acquisition, consolidation and/or recall of memory.

Amnesia↗

PubMed1995

Antioxidant effects of "beta catechin".

The free radical scavenging effect of "beta catechin", an antioxidant preparation containing green tea extract, ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E, was evaluated. Two techniques were used: electron spin resonance (ESR) spectrometry to measure radical-scavenging activity, and measurement of its effect on iron-induced lipid peroxidation in brain. A 0.05% solution of "beta catechin" completely scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals (6.1 x 10(15)spins/ml). A 10% solution of "beta catechin" completely scavenged superoxide (4.2 x 10(15) spins/ml) generated by the hypoxanthine-xanthine oxidase system. An undiluted solution of "beta catechin" scavenged about 90% of hydroxyl radicals (3.5 x 10(15) spins/ml) generated by the Fenton reaction. "beta catechin"s effect on the accumulation of thiobarbituric acid-reactive substances (TBARS) was evaluated from tissue obtained from the ipsilateral cortex of FeCl3-induced epileptic rats. Oral administration of "beta catechin" (1 or 2ml/kg body weight) both inhibited TBARS formation and increased the activity of superoxide dismutase (SOD) in the ipsilateral cortex 30 min after iron-salt injection into the left sensory motor cortex. These data suggest that "beta catechin" has an antioxidant effect and may have a prophylactic effect against aging and other neurological diseases related to free radical mechanisms.

Animals↗

PubMed1994

Behavioral evidence for a modulating role of sigma ligands in memory processes. I. Attenuation of dizocilpine (MK-801)-induced amnesia.

The potentiating effect of low doses of sigma ligands on the N-methyl-D-aspartate (NMDA)-induced excitation of pyramidal CA3 dorsal hippocampal neurons has recently been reported. In the present study, we investigated behavioral effects relevant to these findings in the experimental amnesia induced by the non-competitive NMDA antagonist, dizocilpine (MK-801), in mice. At doses below 1 mg/kg s.c., the sigma ligands, 1,3-di-(2-tolyl)guanidine (DTG), (+)-SKF 10,047, and (+)-pentazocine, but not their (-)-isomers, significantly decreased MK-801 (100 microgram/kg s.c.)-induced impairment of spontaneous alternation performances in 8-min sessions of a Y-maze exploration, an index of spatial working memory, without affecting the concomitant hyperlocomotion. The effect of DTG (100 micrograms/kg s.c.) was completely antagonized by the simultaneous administration of BMY 14802 (10 mg/kg i.p.) and NE-100 (1 mg/kg i.p.), two putative sigma antagonists, which had no effect by themselves. In long-term memory tests (step-down and step-through types of passive avoidance, elevated plus-maze), DTG exhibited a significant attenuation of MK-801-induced amnesia, at doses of 10 and 100 micrograms/kg s.c. In all tests of short- and long-term memory, the effects exhibited by the sigma ligands tested had a bell-shaped curve; no effect was seen at 1 mg/kg. DTG did not affect the impairment of alternation induced by CPP (5 mg/kg i.p.): the modulation may selectively target the blockade of NMDA receptor-associated ion channels. Moreover, DTG (1-1000 micrograms/kg) did not affect the impairment induced by scopolamine (1 mg/kg i.p.) or diazepam (4 mg/kg i.p.), but significantly prevented the impairment induced by mecamylamine (10 mg/kg i.p.). These results suggest that the potentiating effect of sigma ligands on NMDA receptor-mediated glutamatergic neurotransmission, already demonstrated electrophysiologically, may have some relevance to learning and memory processes in the hippocampus. A similar modulation may also affect cholinergic nicotinic systems.

Amnesia↗

PubMed1994

Behavioral evidence for a modulating role of sigma ligands in memory processes. II. Reversion of carbon monoxide-induced amnesia.

This study examined the effect of low doses of sigma ligands on amnesia induced in mice by successive carbon monoxide (CO) exposure. Mice were exposed three consecutive times to CO (10 ml/min, 30-50 s) at 38 degrees C. Spatial working memory impairment was investigated 5 days later by monitoring spontaneous alternation behavior in a Y-maze. Delayed amnesia was examined 7 days after CO exposure by using a step-down passive avoidance test. The preadministration of the sigma ligand 1,3-di-(2-tolyl)guanidine (DTG), at doses of 1 to 1000 microgram/kg, s.c., 30 min before CO exposure did not affect the resulting amnesia in either test. However, when administered 30 min before the test, i.e., 5 or 7 days after CO exposure, this agent completely reversed the CO-induced decrease in alternation performance, at doses of 10 to 100 micrograms/kg. The same effect was observed with (+)-N-allylnormetazocine ((+)-SKF 10,047), at doses of 100 to 300 micrograms/kg, but not with (-)-SKF 10,047. DTG, at the same dose range that reversed the decrease in alternation, also totally reversed the CO-induced decrease in step-down latency in the passive avoidance test. The curve for these effects was bell-shaped; the effects were not observed at the dose of 1 mg/kg. Moreover, alpha-(4-fluorophenyl-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a putative sigma antagonist (1-10 mg/kg i.p.), did not affect CO-induced amnesia, but when simultaneously administered with DTG, it completely prevented its effect in both tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

PubMed1994

The capacity of the malate-aspartate shuttle differs between periportal and perivenous hepatocytes from rats.

The capacity of the malate-aspartate shuttle was evaluated in periportal (PP-H) and perivenous subfraction of rat hepatocytes (PV-H). The rate of glutamine production from alanine was 34-fold higher in PV-H than in PP-H. Statistically significant differences between PP-H and PV-H were found for the activities of lactate dehydrogenase and pyruvate kinase but not for the activities of NAD(+)-malate dehydrogenase, aspartate aminotransferase, and mitochondrial alanine aminotransferase. The rate of glucose production from sorbitol and the rate of ethanol utilization were higher in PP-H than in PV-H. In the presence of phenazine methosulfate (PMS), the increments in these rates were significantly greater in PV-H than in PP-H. The capacity of malate-aspartate shuttle in the presence of alanine was significantly higher in PP-H than in PV-H but in the presence of asparagine was similar in PP-H and PV-H. The results suggest that the capacity of malate-aspartate shuttle distributes heterogeneously along liver lobules with the dominance in periportal zone and that the difference of the capacity may result from the difference in the transport of aspartate across the mitochondrial membrane.

Alanine↗

PubMed1994

The effects of MK-801 on body temperature and behavior in the rat: cross-sensitization and cross-tolerance with phencyclidine.

The purpose of the present study was to compare the acute and repeated administration of MK-801 (dizocilpine) on body temperature and behavior in the rat, and to determine whether there is cross-tolerance and/or cross-sensitization to phencyclidine (PCP) after repeated administration of MK-801. The acute administration of MK-801 increased body temperature, and this response was enhanced after repeated drug administration. PCP had little effect on body temperature in control rats, but produced increases in body temperature in rats treated daily with MK-801. The acute administration of MK-801 produced ataxia, locomotion, sniffing, and head-weaving, and after repeated drug administration both ataxia and head-weaving were reduced. PCP-induced ataxia, backpedalling, head-weaving, and turning behaviors were decreased in rats treated daily with MK-801, but PCP-induced locomotion and rearing were increased. These results indicate that there is cross-sensitization to the hyperthermic and locomotor effects of MK-801 and PCP, but there is cross-tolerance to some of the other behavioral effects of the drugs.

Animals↗

PubMed1994

Immunohistochemical analysis of EGF in epiphyseal growth plate from normal, hypophysectomized, and growth hormone-treated hypophysectomized rats.

Epiphyseal growth plate cartilages from the proximal tibia of normal, hypophysectomized, and growth hormone (GH)-treated hypophysectomized rats were subjected to immunohistochemistry for detection of epidermal growth factor (EGF). In the normal growth plate, EGF was distributed mainly in the proliferative zone. Hypophysectomy resulted in considerable atrophy of the chondrocytes and the cartilage matrix (a decreased number of mature-type chondrocytes and a decreased ratio of proliferating to hypertrophic chondrocytes) and a significant diminution of EGF immunoreactivity. Treatment with GH reversed these effects of hypophysectomy, causing an increased thickness of the growth plate and EGF-reactive sites in all chondrocyte layers. The most intense immunostaining for EGF, however, was frequently seen in the nuclei of chondrocytes with flattened appearance. It appears that EGF could be incorporated or synthesized in chondrocytes having marked mitogenic activity. The present results, taken with previous data on EGF involvement in growth of cartilaginous tissue in vivo and in vitro, strongly suggest that EGF-immunoreactive chondrocytes are involved in cartilage proliferation and growth under the specific influence of GH.

Animals↗

PubMed1994

Inhibitory effects of calcium antagonists on mitochondrial swelling induced by lipid peroxidation or arachidonic acid in the rat brain in vitro.

Inhibitory effects of calcium antagonists, efonidipine (NZ-105), nicardipine, nifedipine, nimodipine and flunarizine, on mitochondrial swelling induced by lipid peroxidation or arachidonic acid in the rat brain in vitro were investigated. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid system showed a close and significant relationship. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid were inhibited by all of calcium antagonists tested. The order of inhibition was: flunarizine > nicardipine > efonidipine > nimodipine > nifedipine. This result suggests that calcium antagonists tested have anti-peroxidant activities resulting in protection of mitochondrial membrane damage and that each moiety of these structures would play an important role in appearance of anti-peroxidant activities. Furthermore, flunarizine and efonidipine inhibited mitochondrial swelling induced by arachidonic acid, which is not associated with lipid peroxidation. In contrast, nicardipine, nifedipine, and nimodipine did not inhibited this swelling. It is possible that flunarizine and efonidipine could directly interact with mitochondrial membrane. In conclusion, it is capable that calcium antagonists tested may protect from the membrane damage induced by lipid peroxidation and that flunarizine and efonidipine could stabilize the membrane, which is attributed to a direct interaction with the membrane.

Animals↗

PubMed1994

Metal ions affect neuronal membrane fluidity of rat cerebral cortex.

The effect of various metal ions on neuronal membrane fluidity was examined using 2-(14-carboxypropyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy, which has been used for the examination of membrane fluidity in hydrophobic areas by electron spin resonance spectrometry. Potassium, cobalt, calcium, magnesium, nickel, copper, ferric, and aluminium ions decreased the membrane fluidity while ferrous ions increased it at each high concentration. Sodium and zinc ions had no effect. Ethylenediaminetetraacetic acid decreased membrane fluidity at high concentrations. Nicardipine lowered membrane fluidity and flunarizine elevated it at each high concentration. There was no change in membrane fluidity by other calcium antagonists, nimodipine and nifedipine.

Animals↗

PubMed1994

Nootropic effect of nicotine on carbon monoxide (CO)-induced delayed amnesia in mice.

The effects of nicotine on carbon monoxide (CO)-induced amnesia in mice were investigated using a step-down type passive avoidance task. Mice were exposed to CO 3 times at 1-h intervals, 7 days before the first training and retention test and 24 h after the first training session. Memory deficiency occurred in mice when training commenced more than 3 days after CO exposure (delayed amnesia): the median step-down latency in the retention test of the CO-exposed group was significantly shorter than that of the control group. Administration of (-)-nicotine (15.6 and 31.3 nmol/kg, IP) 15 min before the first training session prolonged the step-down latency in the CO-exposed group, but (+)-nicotine did not. To determine whether this effect of (-)-nicotine was mediated via nicotinic cholinergic receptors, we attempted to block its action using a nicotinic acetylcholine receptor antagonist (mecamylamine). Mecamylamine (1.25 mumol/kg) blocked the effect of (-)-nicotine (31.3 nmol/kg) on delayed amnesia. Administration of (-)-nicotine (15.6-62.5 nmol/kg) immediately after the first training session failed to ameliorate learning ability in the CO-exposed group. These results suggest that (-)-nicotine potentiates the nicotinic cholinergic neuronal system and may potentiate acquisition of memory.

Amnesia↗

PubMed1994

Low dose of 1,3-di(2-tolyl)guanidine (DTG) attenuates MK-801-induced spatial working memory impairment in mice.

MK-801 (30-100 micrograms/kg, SC) impaired spontaneous alternation behavior of mice, a behavior related to the spatial working memory. 1,3-Di-(2-tolyl)guanidine (DTG), (+)-pentazocine and (+)-SKF 10,047 (100 micrograms/kg, SC), putative sigma agonists, administered 10 min before MK-801, partially but significantly reversed the impairment, without affecting the concomitant hyperlocomotion. The antagonizing effects by DTG were prevented by BMY-14802 (5 mg/kg, IP), a purported sigma antagonist. These findings suggest that, at low doses, sigma ligands may modulate the N-methyl-D-aspartate dependent memory processes.

Animals↗

PubMed1994

Changes in concentrations of dopamine, serotonin, and their metabolites induced by carbon monoxide (CO) in the rat striatum as determined by in vivo microdialysis.

Striatal microdialysis was performed in rats exposed to carbon monoxide (CO). Extracellular changes of dopamine, serotonin, and their metabolites were monitored before and after CO exposure at 15-min intervals by HPLC analysis. After CO exposure, extracellular dopamine increased (3.8 times that of baseline), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (by 20-25% of baseline). The decrease in HVA at individual time points, however, was not significant. After a transient increment of the dopamine, it was cleared from the extracellular fluid within 45 min and reached a stable level. Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) showed a pattern different to that of dopamine and its acid metabolites, i.e., the changes in extracellular levels were small. Pretreatment with dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, 45 min before CO exposure antagonized the changes in the extracellular concentration of DOPAC. However, the change in dopamine levels was not antagonized by pretreatment with MK-801. MK-801 itself had no effect on the levels of monoamines. Therefore, NMDA receptors may not have an important role for regulating striatal dopamine neurons in hypoxic condition.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Probucol scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited formation of thiobarbituric acid reactive substances.

Probucol is suggested to have antioxidant properties. The direct scavenging action of probucol on hydroxyl radicals, superoxide and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were examined using electron spin resonance (ESR) spectrometry. Probucol scavenged DPPH radicals dose dependently but showed no effect on hydroxyl radicals and superoxide generated by Fenton reaction and by hypoxanthine-xanthine oxidase system, respectively. It inhibited the formation of thiobarbituric acid reactive substances (TBARS) in rat cortex homogenate induced by ascorbic acid and FeCl2 at low dose, but it increased TBARS formation at high doses. Probucol showed no effect on the carbon centered radicals. Iron injection into the rat cortex, which is an experimental model for traumatic epilepsy, increased TBARS level in the cortex, hippocampus, striatum and cerebellum, but pretreatment with probucol inhibited the increase in these brain parts except for the hippocampus. These results suggest that the antioxidant property of probucol is partly due to its free radical scavenging effect.

Animals↗

PubMed1994

Application of an alpha-sidechain length-specific monoclonal antibody to immunoaffinity purification and enzyme immunoassay of 2,3-dinor-6-keto-prostaglandin F1 alpha from human urine.

2,3-Dinor-6-keto-prostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha) is a major urinary metabolite of PGI2 (prostacyclin) and one of the most reliable parameters of PGI2 production in vivo. A mouse was immunized with 2,3-dinor-6-keto-20-carboxy-PGF1 alpha conjugated to bovine serum albumin for preparation of a monoclonal antibody which recognized the difference in the alpha-sidechain length of 6-keto-PGF1 alpha and its 2,3-dinor-metabolite. A sensitive and specific enzyme immunoassay was developed by the solid-phase competition method with 2,3-dinor-6-keto-20-carboxy-PGF1 alpha labeled with peroxidase protein. The detection range of the assay was 14-1200 fmol (IC50 = 120 fmol). The cross-reactivities of the antibody with 6-keto-PGF1 alpha, 6,15-diketo-13,14-dihydro-PGF1 alpha, and other arachidonate metabolites were less than 0.01%. An immunoaffinity column was prepared by coupling the anti-2,3-dinor-6-keto-PGF1 alpha antibody to BrCN-activated Sepharose 4B. Human urine was applied to an octadecylsilyl silica cartridge, and the extract was applied to the immunoaffinity column. This procedure allowed an efficient separation of 2,3-dinor-6-keto-PGF1 alpha from unidentified urinary substances which interfered with immunoassay. Validity of the results obtained by the enzyme immunoassay was confirmed by GC/MS employing selected ion monitoring for quantification.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland.

Developmental changes in the hormonal effects on the concentration of epidermal growth factor (EGF) in the rat submandibular gland were investigated. The level of EGF in the gland gradually increased with age from 4 up to 8 weeks of age; thereafter it increased markedly, reaching a plateau level at 12 weeks of age in both male and female rats. A significant sex difference in EGF levels was observed between 8 and 14 weeks, the level in the males being approximately twice as high as that in the females at 12 and 14 weeks of age. Castration of male rats decreased EGF to about the same level as that of control females. Treatment of castrated rats with testosterone propionate (TP) restored EGF to the levels in control male rats. Ovariectomy and/or administration of oestradiol-17 beta to ovariectomized rats had no apparent effect on EGF concentration. These findings indicate that the sex difference in EGF concentration can be attributed to the level of endogenous androgens. In addition, hypophysectomy of male rats caused a remarkable decrease in submandibular gland EGF to about 7% of the normal level. This reduction was significantly, although not completely, restored by the administration of TP, triiodothyronine (T3) or GH. Moreover, giving TP with T3 or with GH or both together had additive effects on the increase in EGF levels in hypophysectomized rats. These results provide evidence that EGF in the submandibular gland is regulated multihormonally by at least TP, T3 and GH.

Aging↗

PubMed1994

Effects of alcohol on membrane fluidity of human erythrocyte.

Membrane fluidity in human erythrocytes was measured by a spin label method using an electron spin resonance spectrometer in healthy volunteers after ingestion of alcohol (1.5 ml of whisky/kg body weight). Fluidity in the lipid bilayer closer to the hydrophilic face decreased at 30 min and 90 min, and fluidity in the hydrophobic core decreased at 90 min after ingestion of alcohol. In the same experiment, the level of thiobarbituric acid reactive substances in the serum decreased 30 min after ingestion of alcohol, and the triglyceride level increased and free fatty acid level decreased, and serum superoxide dismutase activity increased 150 min after ingestion. Furthermore, membrane fluidity in human erythrocytes was examined in patients with alcohol dependence syndrome who had not any alcohol for about 26 months. Erythrocyte membrane fluidity of patients with alcohol dependence syndrome was not different from that of healthy controls. However, erythrocyte membrane fluidity of the lipid bilayer closer to the hydrophilic face increased in patients who had concomitant liver cirrhosis compared with those who did not. These results suggest that alcohol affects temporal change of membrane fluidity in human erythrocytes.

Adult↗

PubMed1994

[Experimental techniques for developing new drugs acting on dementia (6)--Carbon monoxide-induced amnesia model in experimental animals].

Cell death, neuronal dysfunction and deterioration of memory function can be produced after carbon monoxide exposure in mice as in human. These deficiencies are developed in a delayed manner (delayed amnesia). The neurotoxicity of excitatory amino acids may be involved in this model, since dizocilpine (MK-801) fully protects against carbon monoxide-induced cell death, learning impairment and delayed amnesia. In the present paper, we described the method of carbon monoxide exposure and the characteristic of behavioral and biochemical changes after carbon monoxide exposure. These data indicate that carbon monoxide can provide an amnesic model for the investigation of memory deterioration and the development of new anti-amnesic drugs.

Amnesia↗

PubMed1994

(+-)-1-Amino-1,3-cyclopentane-trans-dicarboxylic acid (trans-ACPD) induced inositol triphosphoric acid formation in the brain of iron-induced epileptic rats and epileptic El mice.

Myo-inositol-1,4,5-triphosphoric acid (IP3) formation stimulated by (+-)-1-amino-1,3-cyclopentane-trans-dicarboxylic acid (trans-ACPD) was examined in the cortex, hippocampus and cerebellum of iron-induced epileptic rats and epileptic El mice. Increased IP3 formation by trans-ACPD was observed in the cortex, hippocampus and cerebellum of iron-injected rats while it was found in the hippocampus and cerebellum of the saline-injected control rats. Increased IP3 formation by trans-ACPD was remarkably higher in the hippocampus of iron-injected rats than the other regions. Increased IP3 formation by trans-ACPD was observed in the cortex, hippocampus and cerebellum of ddY mice, while such an increase was found only in the cerebral cortex and not in the hippocampus and cerebellum of El mice. These findings suggest that the inositol response may be involved in the seizure mechanisms of iron-induced epileptic rats and epileptic El mice in some different forms.

Animals↗