Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 217 records · Page 12Linked to original sources

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

Sensitive colorimetric assay of serum diamine oxidase.

A simple and sensitive colorimetric assay for serum diamine oxidase (DAO) activity was based on a coupled reaction with peroxidase and a new chromogen, 10-(carboxymethyl-aminocarbonyl)-3,7-bis(dimethylamino) phenothiazine sodium salt (DA-67). In the presence of peroxidase and DA-67, peroxidase catalyzes the formation of methylene blue having an absorption maximum at 668 nm. The proposed method eliminates the interferences occurring in serum with use of ascorbate oxidase and stops the reaction with sodium diethyldithiocarbamate, leaving the methylene blue in the reaction mixture stable for about 2 h. Low normal basal values of serum DAO can be determined in the range 2.8-9.0 units/l. Since all reagents are commercially available the method is suitable for the clinical laboratory.

Adolescent↗

PubMed1994

Changes in muscarinic cholinergic, PCP, GABAA, D1, and 5-HT2A receptor binding, but not in benzodiazepine receptor binding in the brains of aged rats.

We used in vitro quantitative autoradiography to investigate changes in neurotransmitter receptor binding, including muscarinic cholinergic, PCP, GABAA, benzodiazepine, D1 and 5-HT2A receptor, in the brains of aged rats, compared with such binding in young rats. Scatchard analysis revealed that the maximal number of binding sites for [3H]quinuclidinyl benzilate (QNB) in the caudate/putamen and accumbens was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. The specific binding of [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) for the ion channels coupled with N-methyl-D-aspartate receptors in the caudate/putamen and hippocampus was significantly decreased in aged rats compared with young rats. The [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding was not changed in any brain regions. The [3H]SCH23390 binding for dopamine D1 receptors was significantly increased in the parietal cortex, but decreased in the caudate/putamen and accumbens of aged rats compared with that in young rats. The [3H]ketanserin binding for 5-HT2A receptors in the cortex and accumbens was significantly decreased in aged rats compared with young rats. These results suggest that uneven changes in receptors for various neurotransmitters throughout the brain may be responsible for the decline of brain function in aged rats.

Aging↗

PubMed1994

Omega-conotoxin GVIA protects against ischemia-induced neuronal death in the Mongolian gerbil but not against quinolinic acid-induced neurotoxicity in the rat.

Excessive release of neurotransmitters is reported to contribute to the delayed neuronal death in animal models of cerebral ischemia. Since evidence is accumulating that N-type voltage-sensitive calcium channels (N-channels) regulate the release of neurotransmitters, we investigated the effects of omega-conotoxin GVIA (omega-CTX), an antagonist of N-channels, on delayed neuronal death following transient ischemia in gerbils. Delayed neuronal death in the CA1 subfield of the hippocampus following 5-min ischemia was attenuated by omega-CTX in a dose-dependent manner when the agent was injected intracisternally 1 hr before ischemia was produced. However, omega-CTX failed to prevent neurotoxicity produced by a direct injection of quinolinic acid into the hippocampus in rats. These results suggest that omega-CTX has a neuroprotective effect against ischemic brain injury, which effect probably results from its inhibition of the excessive release of neurotransmitters, including excitatory amino acids, during ischemia.

Animals↗

PubMed1994

Nicotine reverses scopolamine-induced impairment of performance in passive avoidance task in rats through its action on the dopaminergic neuronal system.

Interest has recently focused on tobacco and/or nicotine in relation to senile dementia of the Alzheimer type because the population of patients with this disease among tobacco smokers is significantly smaller than in nonsmokers. We investigated whether, in relation to the dopaminergic neuronal system, nicotine was effective in ameliorating the impairment of performance in passive avoidance tasks in rats induced by scopolamine, an inhibitor of muscarinic acetylcholine receptors. Scopolamine and nicotine were coadministered to rats 30 min before the acquisition trial. Some rats received scopolamine alone; they showed much shorter step-through latency (STL) than the control group in the retention test. Nicotine significantly prolonged the decreased STL induced by scopolamine. The effects of nicotine were inhibited by the preadministration of mecamylamine, SCH 23390, and (-)sulpiride, which are nicotinic acetylcholine, D1, and D2 receptor antagonists, respectively. These results suggest that nicotine, by activating the nicotinic acetylcholinergic and dopaminergic neuronal systems, ameliorates the impairment of performance in the passive avoidance task induced by a muscarinic acetylcholine receptor blocker.

Animals↗

PubMed1994

PRE-084, a sigma selective PCP derivative, attenuates MK-801-induced impairment of learning in mice.

We investigated the effect of the sigma selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK-801. Learning capacities were evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that sigma sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at sigma sites, reverses the amnesia induced by a drug acting at the PCP site.

Amnesia↗

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

Effect of a single injection of psychoactive drugs on CCK mRNA in rat brain.

The acute and long-term effects of a single injection of psychoactive drugs, methamphetamine or phencyclidine, were investigated by Northern blot to assess alterations in the cholecystokinin (CCK) mRNA in three areas of the rat brain. In the frontal cortex, there were no significant changes in CCK mRNA after the drug injection. In contrast, decreases in CCK mRNA were observed in the posterior cortex and the hippocampus from 30 min to 48 h after the drug treatment. The data suggest that CCK gene expression has different sensitivity to these psychoactive drugs within the cortices.

Animals↗

PubMed1994

Influence of age on the disposition and renal handling of enprofylline in rats.

The effects of ageing on the pharmacokinetics, renal handling and protein binding of enprofylline were investigated in 6-, 13- and 18-month-old male Fischer 344 rats. Concentrations of enprofylline in plasma and urine were determined by HPLC, and pharmacokinetic parameters were estimated by model-independent methods. No significant differences in the volume of distribution, systemic clearance of enprofylline or urinary recovery of unchanged enprofylline (> 85%) were observed among any of the groups of rats. The dissociation constant and free fatty acid concentration in plasma increased with age. Age-dependent decreases in the systemic clearance for unbound drug were observed, and the volume of distribution for unbound drug tended to decrease with age. The ratio of systemic clearance for unbound drug to the glomerular filtration rate (GFR) decreased with ageing. Ageing was associated with decreases in the apparent maximum capacity of transport (Vmax)(223.33, 160.24 and 142.98 micrograms min-1 kg-1 for 6-, 13- and 18-month-old rats, respectively) and in the tubular secretory intrinsic clearance (Vmax/Km) of enprofylline (75.45, 51.03 and 44.13 mL min-1 kg-1, respectively), while a slight change in the Michaelis-Menten constant (Km) was observed. These results indicate that the mechanism responsible for age-related changes in the disposition and renal handling of enprofylline may be responsible for a decrease in the ability of the tubular anion transport system.

Aging↗

PubMed1994

Pharmacokinetic characteristics of 5-fluorouracil and mitomycin C in intraperitoneal chemotherapy.

Eight patients with malignancies confined to the peritoneal space participated in this study. Five hundred milligrams 5-fluorouracil or 10 mg mitomycin C was diluted in 1 L saline. The mixed solution was injected intraperitoneally through the semi-permanent peritoneal catheter. Blood and peritoneal fluid were collected after injection. 5-Fluorouracil concentrations in the peritoneal fluid were 1000 times those in serum, while mitomycin C concentrations were 100 times those in serum. Areas under the concentration vs time curve (AUC) were calculated by the trapezoidal method with extrapolation to infinity. The ratio of peritoneal fluid AUC to serum AUC was about 1400 for 5-fluorouracil and 80 for mitomycin C. Patterns for the absorption and elimination from systemic circulation were similar for both compounds. Drug concentrations in the peritoneal fluid and serum were analysed according to the compartment model. The half-life in the peritoneal fluid (t1/2p) and the rate constant from the peritoneal fluid to the systemic circulation (ka) were nearly equal for both 5-fluorouracil and mitomycin C (t1/2p, 1.0 h for 5-fluorouracil and 1.3 h for mitomycin C; ka 0.71 h-1 for 5-fluorouracil and 0.68 h-1 for mitomycin C), although the apparent volume of distribution (Vds/F) and clearance in the peritoneal cavity (CLp) for mitomycin C (78 L m-2 and 1.8 L h-1 m-2) were about twice the values for 5-fluorouracil (149 L m-2 and 0.8 L h-1 m-2).

Absorption↗

PubMed1994

Oral administration of NGF synthesis stimulators recovers reduced brain NGF content in aged rats and cognitive dysfunction in basal-forebrain-lesioned rats.

Nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. Since this factor does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We report here that repeated oral administration of the stimulators for the NGF synthesis, idebenone and propentofylline, produced a significant recovery of the reduced NGF content in the frontal and parietal cortices of aged rats. These compounds also improved deficits of performance in water maze, passive avoidance and habituation tasks in basal-forebrain-lesioned rats. These results suggest that the use of the stimulators for the NGF synthesis may provide a therapeutic approach to cholinergic dysfunction.

Administration, Oral↗

PubMed1994

Effects of kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography: changes in dopamine D1 and serotonin 5-HT2A receptor binding.

Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT), a traditional Chinese medicine, on specific [3H]SCH23390 binding to dopamine D1 receptors and [3H]ketanserine binding to serotonin 5-HT2A receptors in the rat brain. Specific binding of both compounds was affected by aging. Long-term administration of KKT resulted in decreases in [3H]SCH23390 binding to the cortex and hippocampus in aged rats, and in decreases in [3H]ketanserine binding to the caudate/putamen in young rats. These results suggest that the changes in dopamine Di and serotonin 5-HT2A receptor binding may be involved in the central effects of KKT.

Aging↗

PubMed1994

Influence of endotoxin and lipid A on the renal handling and accumulation of gentamicin in rats.

The contribution of lipid A, an active component of endotoxin (LPS), to changes in the pharmacokinetics, renal handling and intrarenal accumulation of gentamicin induced by Klebsiella pneumoniae LPS was investigated in rats. Either LPS (250 micrograms/kg) or lipid A (equivalent to dose of LPS) was infused 2 h before the administration of gentamicin (10 mg/kg). The effects of LPS and lipid A on the intrarenal accumulation of gentamicin were also evaluated. Significant increases in the levels of plasma creatinine and blood urea nitrogen were observed in both the LPS and lipid A groups. Both LPS and lipid A induced significant decreases in the glomerular filtration rate (by approximately 30%) and systemic clearance of gentamicin (by approximately 25%). No changes in the fraction of urinary excretion (> 0.9) or steady-state volume of distribution of gentamicin were observed between either the control, LPS or lipid A groups. There were no significant differences among the three groups in the tubular reabsorption or intrarenal accumulation of gentamicin. The degree of effect of lipid A on the pharmacokinetics of gentamicin observed in this study was nearly equal to that of LPS. These results suggest that lipid A plays a major role in changes in the pharmacokinetics and renal handling of gentamicin induced by LPS.

Animals↗

PubMed1994

Nerve growth factor content of rat brain increases following basal-forebrain lesions induced by ibotenic acid but not by electrolysis.

We attempted to measure the change in the nerve growth factor (NGF) content in the hippocampus and parietal cortex following basal-forebrain lesions induced by ibotenic acid and electrolysis. The NGF content of the parietal cortex and hippocampus increased transiently on days 3 to 7, and then returned to the control level on day 14 after the lesion of the basal forebrain induced by ibotenic acid. Ibotenic acid decreased both the choline acetyltransferase (ChAT) activity in the parietal cortex and the dopamine content in the striatum. Electrolytic lesions of the basal forebrain decreased the dopamine content in the striatum, but did not affect the NGF content and ChAT activity in any of the brain regions examined. These results suggest that the mechanism of NGF synthesis is related to cholinergic, but not to dopaminergic, neurons in the basal forebrain.

Analysis of Variance↗

PubMed1994

Effects of kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography (1): Changes in the [3H]QNB binding.

Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT), a traditional Chinese medicine, on the specific binding of [3H]quinuclidinyl benzilate (QNB) and [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine (TCP) in the rat brain. The Bmax but not the Kd values for [3H]QNB binding to the caudate/putamen and accumbens in aged rats were lower than those in young rats. The [3H]TCP binding was also decreased in aged rats compared with that in young rats. Long-term administration of KKT modulated the [3H]QNB binding in young but not aged rats.

Aging↗

PubMed1994

Anticancer effects of adriamycin-loaded hydroxyapatite implants determined in a Swarm rat chondrosarcoma model.

We investigated the antitumor effects of adriamycin (ADR)-loaded hydroxyapatite (HAP) beads in a Swarm rat chondrosarcoma model. When one ADR-loaded HAP bead (ADR: 0.8 mg/bead) was implanted into the central portion of a rat bearing tumor, the ADR-loaded HAP beads showed good therapeutic effects, increasing the life span (ILS) by 90%. Significantly, leukopenia and diarrhea were not observed. These results suggest that HAP delivery offers an interesting and a potentially effective method.

Animals↗

PubMed1994

Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin.

In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.

3,4-Dihydroxyphenylacetic Acid↗