PubMed Health⌕ Search

Biomedical subjects

Toshitaka Nabeshima

Publications and source records attributed to Toshitaka Nabeshima.

At least 91 records · Page 5Linked to original sources
PubMed2004

PAP 9704, a Korean herbal medicine attenuates methamphetamine-induced hyperlocomotion via adenosine A2A receptor stimulation in mice.

The effect of PAP 9704, a traditional prescription in Korea consisting of Polygala tenuifolia, Acorus gramineus, and Poria cocos at a ratio of 1:1:1 (dry weight), on methamphetamine (MA)-induced hyperlocomotion was examined in mice. The increased locomotor activity induced by MA (1 mg/kg/d, i.p. x 7) was significantly attenuated by co-administration with PAP 9704 (100 or 200 mg/kg/d, p.o. x 7) in a dose dependent manner. Consistently, it was found that the hyperlocomotor activity occurred in parallel with the expression of striatal fos-related antigen immunoreactivity. The adenosine A(2A) receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1.0 mg/kg, i.p.), significantly reversed the pharmacological action of PAP 9704 in a dose related manner, but the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) and the A(2B) receptor antagonist alloxazine (1.5 or 3.0 mg/kg, i.p.) did not significantly affect this pharmacological action. Our results suggest that PAP 9704 prevents MA-induced hyperlocomotion, at least in part, via the stimulation of the adenosine A(2A) receptor.

Animals↗
PubMed2004

Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play important roles in learning and memory. Memory acquisition is associated with an increase in BDNF mRNA and TrkB activation in specific brain areas. Pharmacologic and genetic deprivation of BDNF or TrkB results in an impairment of memory. Activation of the mitogen-associated protein kinase and phosphatidylinositol 3-kinase signaling pathways is involved in BDNF-dependent learning and memory. A frequent single nucleotide polymorphism in the targeting region of the human BDNF gene (val66met) is associated with poorer episodic memory and abnormal hippocampal neuronal function in humans. The interaction of BDNF/TrkB signaling with N-methyl-D-aspartate receptors is important for spatial learning and memory, and an Src-family tyrosine kinase Fyn may play a key role in this interaction by linking TrkB with NR2B.

Animals↗
PubMed2004

[Infection control in neutropenia induced by high-dose cytarabine chemotherapy].

A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML). Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy. The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05). The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria.

Adolescent↗
PubMed2004

[Neuroprotective effects of magnesium on cerebral ischemia and cerebral contusion].

Neuroprotective effects of magnesium (Mg(2+)) have been shown in experimental studies by using animal models of the cerebral ischemia and cerebral contusion. We review the neuroprotective effects of Mg(2+) in the histological and behavioral studies. In the animal models of cerebral ischemia, Mg(2+) treatment reduces the infarct volume, inhibits the neuronal death, and attenuates the motor impairments. In the animal models of cerebral contusion, Mg(2+) treatment inhibits the neuronal death and edema, and attenuates not only the motor impairments but also cognitive dysfunction.

Animals↗
PubMed2003

Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients.

BACKGROUND: Cyclosporine A (CsA) is a critical immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Many factors, including P-glycoprotein (PGP), influence the oral bioavailability and interpatient variability of CsA. A number of polymorphisms have been identified in the human MDR1 gene, and some of them have been found to be associated with an altered expression of PGP. We have investigated the role of these polymorphisms in CsA absorption from kidney transplant recipients. In addition, we also investigated the effect of amlodipine on CsA absorption. METHODS: The area under the time-concentration curve from 0 to 2 hr (AUC(0-2)) estimated by the trapezoidal rule was used for the evaluation of extent of CsA absorption. The genotypes were identified by a polymerase chain reaction, restriction fragment length polymorphism analysis. RESULTS: No association was found between polymorphisms in the MDR1 and CsA AUC(0-2)/dose/kg. In contrast, the combination of amlodipine significantly increased CsA AUC(0-2)/dose/kg (706.2 microg x hr/L to 819.2 microg x hr/L, P<0.05). Furthermore, we attempted to compare MDR1 polymorphisms and the absorption of CsA again without patients receiving amlodipine, but there was still no significant difference. CONCLUSIONS: There is no relationship between polymorphisms for MDR1 and CsA absorption, suggesting polymorphisms for MDR1 cannot account for the interpatient variability of CsA. Amlodipine, which is the substrate of PGP, significantly increased CsA absorption. These results indicate that PGP plays a significant role in CsA absorption, but its polymorphisms could not influence the CsA absorption.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Role of the mesotelencephalic dopamine system in learning and memory processes in the rat.

The effects of lesioning the ventral tegmental area or substantia nigra pars reticulata by means of bilateral microinjections of two doses of kainic acid (50 ng/250 nl and 100 ng/500 nl) or 6-hydroxydopamine (8 microg/4 microl) were investigated to clarify the role of the mesotelencephalic dopamine system in learning and memory processes. Our findings suggest that ventral tegmental area and substantia nigra dopaminergic neurons play an important role in retention of both short-term memory, tested in the Y-maze task and long-term memory evaluated with the multi-trial passive avoidance test, without affecting memory acquisition. As compared to short-term memory, long-term memory is more susceptible to the decreased dopamine level in nervous structures involved in processing and storage of information.

Animals↗
PubMed2003

Effects of nicotine on memory impairment induced by blockade of muscarinic, nicotinic and dopamine D2 receptors in rats.

Scopolamine dose-dependently inhibits passive avoidance latency and decreases spontaneous alternation in the Y-maze, suggesting effects on long-term and short-term memory, respectively. Chlorisondamine (10 mg/kg), a compound which produces a long-lasting central nicotinic receptor blockade, did not affect short-term and long-term memory performance. In normal rats, nicotine at the doses of 0.3, 1.0, and 3.0 mg/kg administered once had a facilitating effect on short-term memory; a higher dose (3.0 mg/kg) did not show a more pronounced effect than a lower one (0.3 mg/kg). Nicotine, by activating the nicotinic acetylcholine receptors, attenuated the impairment of short-term memory induced by muscarinic or dopamine D2 receptor blockade. On long-term memory, a single dose of nicotine (0.3, 1.0, 3.0 mg/kg) did not affect memory performance, but improved it after chronic (10 consecutive days, 0.3 mg/kg) administration. The antiamnesic effect of nicotine administered once was observed in scopolamine-, scopolamine+chlorisondamine- or sulpiride-treated rats. These results 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↗
PubMed2003

Mechanism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier.

The serious and characteristic side effects of interferon-alpha (IFN-alpha) therapy on the central nervous system, resulting in such problems as affective disorders or parkinsonism, have led us to investigate the biochemical mechanism of the effects of IFN-alpha on the monoaminergic neurotransmitter system using an animal model (rats). We first examined the concentrations of tetrahydrobiopterin (BH(4)) and monoamines in several regions of the brain after the intramuscular injection of IFN-alpha into rats; the levels of BH(4) and dopamine significantly decreased in the amygdala and raphe areas as compared with those of the controls. Based on these results, we further examined the concentrations of BH(4) and nitrite (NO(2)(-)) plus nitrate (NO(3)(-)), metabolites of nitric oxide (NO), in the amygdala and raphe areas after the intramuscular injection of IFN-alpha; the concentrations of both BH(4) and NO(2)(-)+NO(3)(-) significantly decreased as compared with the control. Furthermore, the addition of N(G)-monomethyl L-arginine, an inhibitor of NO synthase, after the injection of IFN-alpha restored the decreased levels of both NO(2)(-)+NO(3)(-) and BH(4) to control levels. As a result, nitric oxide induced by the intramuscular injection of IFN-alpha was found to cross the blood-brain barrier and suppress both tetrahydrobiopterin biosynthesis and dopamine production in the amygdala and raphe areas.

Animals↗
PubMed2003

Comparative study of acute effects of single doses of fexofenadine, olopatadine, d-chlorpheniramine and placebo on psychomotor function in healthy volunteers.

Since most classical (first-generation) antihistamines have undesirable sedative effects on the central nervous system (CNS), newer (second-generation) antihistamines have been developed to relieve the sedative effects and to improve the patient's quality of life. However, the psychomotor profiles of second-generation antihistamines are not fully elucidated. In this randomized, double-blind, crossover study, the acute effects of single doses of second-generation antihistamines, fexofenadine (120 mg) and olopatadine (10 mg), on cognitive and psychomotor performance were investigated in comparison with those of placebo and d-chlorpheniramine (4 mg), a first-generation antihistamine, using objective and subjective assessments, in 11 healthy Japanese volunteers. In a battery of psychomotor tests, d-chlorpheniramine impaired tracking ability in the compensatory tracking task and caused a reduction in behavioural activity as continuously measured by wrist actigraphy. Olopatadine, like d-chlorpheniramine, reduced the behavioural activity, while fexofenadine had no effect in any of the tests. No significant changes in the subjects' self-ratings of drowsiness were found with the three antihistamines. These results suggest that d-chlorpheniramine and olopatadine, but not fexofenadine, produce sedative effects on psychomotor performance, and that the CNS profile of fexofenadine is different from that of olopatadine.

Adult↗
PubMed2003

Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis.

Objective of the present study was to investigate the elimination kinetics of quinaprilat and perindoprilat, the active metabolites of angiotensin-converting enzyme (ACE) inhibitors quinapril and perindopril, in hypertensive patients with renal failure under haemodialysis to evaluate the appropriate duration of off-dose of these drugs before starting of low-density lipoprotein (LDL) apheresis. The informed consent was received from 12 hypertensive patients with renal failure, who were under haemodialysis (42 to 62 years). The patients received oral administration of quinapril (10 mg) or perindopril (2 mg) once a day for four weeks. First, to evaluate the dialyzability of each metabolite, blood samples were collected before and after haemodialysis one week after the repeated doses. Second, to evaluate the elimination kinetics of quinaprilat or perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after the final administration. Plasma concentrations of quinaprilat and perindoprilat were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for quinaprilat and 108.1+/-5.9 ml/min and 0.75+/-0.04 for perindoprilat, respectively. The terminal elimination half-lives of quinaprilat and perindoprilat were 60.7+/-2.1 and 79.9+/-14.0 h, respectively. The dialyzability of perindoprilat was much higher than that of quinaprilat probably due to low protein binding potency. The present study suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.

Administration, Oral↗
PubMed2003

Brain-derived neurotrophic factor/TrkB signaling in memory processes.

Activity-dependent changes in synaptic strength are considered mechanisms underlying learning and memory. Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity such as long-term potentiation. Recent experimental evidence supports the role of BDNF in memory processes: Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor TrkB. Genetic as well as pharmacologic deprivation of BDNF or TrkB impairs learning and memory. In a positively motivated radial arm maze test, activation of the TrkB/phosphatidylinositol-3 kinase (PI3-K) signaling pathway in the hippocampus is associated with consolidation of spatial memory through an activation of translational processes. In a negatively motivated passive avoidance test, mitogen-activated protein kinase (MAPK) is activated during acquisition of fear memory. Furthermore, recent findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory. A Src-family tyrosine kinase, Fyn plays a role in this interaction by linking TrkB with NR2B. These findings suggest that BDNF/TrkB signaling in the hippocampus plays a crucial role in learning and memory.

Animals↗
PubMed2003

[Role of cytokines in drug dependence].

Methamphetamine (MAP) is a drug of abuse that has steadily gained in popularity. Repeated use of MAP can cause drug dependence that may lead to serious psychiatric and neurologic signs and symptoms in users. It has recently become accepted that multidirectional communication exists among the immune, hormonal, and central nervous systems. Thus, it is suggested that these communications play an important role in drug dependence. Here we review the role of cytokines in drug dependence.

Amphetamine-Related Disorders↗
PubMed2003

[Effects of sigma receptor ligands on psychiatric disorders].

It has recently been suggested that sigma receptors are involved in psychiatric disorders. Sigma 1 receptor antagonists are effective in animal models of positive symptoms, cognitive deficit and disruption of prepulse inhibition in schizophrenia. They also inhibit the development and expression of the conditioned place preference induced by cocaine. On the other hand, sigma 1 receptor agonists reduce the immobility time in the forced swimming and tail suspension tests. Furthermore, sigma 1 receptor agonists attenuate the conditioned fear stress (CFS) response (which is not attenuated by typical anxiolytics or antidepressants) in rodents. The attenuating effects are mediated through sigma 1 receptors, which are closely related to the mesolimbic dopaminergic systems. Sigma 1 receptor agonists also have anti-amnesic effects in various experimental models. Neurosteroids such as dehydroepiandrosterone sulfate and pregnenolone sulfate attenuate the CFS response and have anti-amnesic effects, the effects being mediated via sigma 1 receptors. These findings suggest that sigma receptors are novel potential targets for the treatment of psychiatric disorders such as schizophrenia, drug abuse, depression and dementia.

Animals↗
PubMed2003

[Cognition impairment in the klotho gene mutant mice and oxidative stress].

Klotho is a recently identified gene that is a very different type from those involved in previously described premature-aging syndromes and cell senescence. Although a high level of expression of the klotho gene was detected in the kidney and brain, little is known about the function of the klotho gene in the brain. Here we investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks, but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and DNA peroxide (8-hydroxy-2'-deoxyguanosine) levels in the hippocampus of klotho mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 weeks. A potent antioxidant alpha-tocopherol prevented the cognition impairment and lipid peroxide accumulation, and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.

Aging↗
PubMed2003

[Candidate genes or compounds for therapeutic tools against methamphetamine and/or morphine-induced dependence].

Drug dependence is one of most severe problems in all over the world, however, the mechanisms and related-genes have not been completely revealed. Here we would like to introduce tumor necrosis factor-alpha (TNF-alpha). Repeated treatment with methamphetamine induced an increase in TNF-alpha mRNA in the some brain regions. Exogenous TNF-alpha blocked the methamphetamine rewarding. TNF-alpha plays a neuroprotective role in methamphetamine drug dependence. These results suggest that TNF-alpha is one of key proteins. TNF-alpha itself might not be therapeutic tools, since it has immunological actions in physical conditions. Therefore, next, we found a stimulator, Leu-Ile, which enhances TNF-alpha synthesis in cultured neurons. Leu-Ile protected blocked the methamphetamine induced rewarding effects. These results suggest that a stimulator of TNF-alpha synthesis may be one of therapeutic tools against drug dependence.

Animals↗
PubMed2002

Memory impairment induced by chronic intracerebroventricular infusion of beta-amyloid (1-40) involves downregulation of protein kinase C.

Signaling pathways underlying the cognitive deficit of the Alzheimer's disease (AD) are not completely understood. Protein kinase C (PKC), a major neuronal protein plays a critical role in cellular signal transduction and it is known to be subjected to modulation in AD. We showed previously that, chronic infusion of beta-amyloid (1-40) into rat cerebroventricle leads to deficit in spatial and non-spatial memory formation. As an attempt to identify the cellular correlates of the memory deficit, in the present study we investigated the PKC activation in different brain areas. Chronic infusion of beta-amyloid (1-40) for 14 days into the rat cerebroventricle decreased the activity of soluble protein kinase C (PKC) in the hippocampus. Subcellular translocation of PKC to membrane fraction in hippocampal slices of rats treated with beta-amyloid (1-40) was completely abolished under acute stimulation with 0.5 microM phorbol-dibutyrate (PDBu). We also reported a decreased affinity (k(D)) for PDBu binding in the hippocampus, cerebral cortex and striatum. The total number of binding sites for PDBu (B(max)) was increased, in the three brain areas analyzed on the day 14, but the changes were not statistically significant. Our data indicate that chronic accumulation of beta-amyloid (1-40) into the rat brain reduced activation of PKC, effect that would substantially contribute to the memory deficit found in these animals.

Alzheimer Disease↗
PubMed2002

Nefiracetam induces a long-lasting facilitation of hippocampal postsynaptic responses in mice lacking the NMDA receptor epsilon1 subunit.

The present study was designed to assess whether the facilitatory action of nefiracetam, a pyrrolidone derivative, on hippocampal postsynaptic responses is dependent upon N-methyl-D-aspartate (NMDA) receptors or not, by monitoring population spikes (PSs) in the dentate gyrus of hippocampal slices from mice lacking the NMDA receptor epsilon1 subunit. Nefiracetam (1 microM) induced a sustained facilitation of postsynaptic responses in the dentate gyrus of hippocampal slices from wild-type mice. The facilitation occluded the potentiation induced by high-frequency stimulation at the perforant path, and vice versa, suggesting a common mechanism between them. The perforant path long-term potentiation (LTP) was not induced in epsilon1 subunit knock-out mice, but nefiracetam (1 microM) persistently potentiated PS amplitude, reaching 280% of basal levels 50 min after 10-min treatment, similar to the potentiation achieved with wild-type mice. The results of the present study, thus, suggest that nefiracetam exerts its facilitatory action on hippocampal postsynaptic responses in an NMDA receptor-independent manner.

Animals↗