Digitalis intoxication induced by paroxetine co-administration.
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Aged↗
Biomedical subjects
Sunao Kaneko
Publications and source records attributed to Sunao Kaneko.
Involvement of Ca(2+)-induced Ca2+ releasing system in interleukin-1beta-associated adenosine release.
Interleukin-1beta (IL-1beta) plays an important role in neuroprotective and neurodegenerative events in the central nervous system. To clarify the mechanism of controversial actions of IL-1beta, we determined the effect of IL-1beta, as well as the interaction between IL-1beta and Ca(2+)-induced Ca2+ releasing system (CICR), on adenosine releases in mice hippocampus using mini-slices method. Basal and K(+)-stimulated adenosine releases were regulated by two types of CICRs, including inositol-1,4,5-trisphosphate (IP3) receptor and ryanodine receptor. Lower concentration of IL-1beta increased both adenosine releases, whereas higher concentration did not affect their releases. The stimulatory effect of IL-1beta on basal adenosine release was reduced by removal of extracellular Ca2+ and IP3 receptor inhibitor, while the stimulatory effect of IL-1beta on K(+)-stimulated adenosine release was reduced by ryanodine receptor inhibitor. These results suggest that the potent effect of IL-1beta upon adenosine release might contribute to the neuroprotective action of IL-1beta, whereas IL-1beta-induced neurodegeneration might be due to the overload response of Ca2+ mobilization and the inactivation of adenosine exocytosis.
Adenosine↗
Determination of genomic breakpoints in an epileptic patient using genotyping array.
Recent advances in DNA microarray technology have enabled the identification of small alterations throughout the genome. We used standard karyotype analysis, followed by DNA microarray analysis and PCR to precisely map the chromosomal 4p deletion and determine the deletion breakpoints in the genome of an epileptic patient. The karyotype of the patient was 46,XY,del(4)(p15.2p15.3) as determined by G-banding analysis. We used a high-density oligonucleotide genotyping array to estimate the size of the deletion (4.5 Mb) and to locate the breakpoints within a 9-kb region on one side of the deletion and a 100-kb region on the other side. We amplified by PCR and sequenced the genomic region encompassing the breakpoints, and mapped the deletion to regions extending from 21648457 to 26164287 and from 26164505 to 26167493, respectively (chromosome 4 of NCBI Homo sapiens Genome Build 35.1). The deletion involves 18 genes, one of which (CCKAR) is partially deleted.
Chromosome Breakage↗
Association between multidrug resistance 1 (MDR1) gene polymorphisms and therapeutic response to bromperidol in schizophrenic patients: a preliminary study.
The drug-transporting P-glycoprotein transports drugs against a concentration gradient across the blood-brain barrier back into the plasma and thereby reduces the bioavailability in the brain. Polymorphisms in the MDR1 gene regulating P-glycoprotein expression can be associated with differences in drug disposition in the brain. The present study was therefore designed to examine whether the major polymorphisms of MDR1 gene, C3435T and G2677T/A are related to therapeutic response to neuroleptics in the treatment of schizophrenia. Subjects consisted of 31 acutely exacerbated schizophrenic inpatients treated with bromperidol (6-18 mg/day). Plasma drug concentrations were monitored and clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The C3435T and G2677T/A genotypes were determined by a polymerase chain reaction method. Schizophrenic symptoms were allocated into 5 clusters: positive, excitement, cognitive, negative, and anxiety-depression symptoms. Patients were C/C in 12, C/T in 12 and T/T in 7 cases for C3435T genotype and G/G in 3, G/T or A in 17 and T or A/T or A in 11 cases for G2677T/A genotype. There were a tendency of difference, but not statistically different, in the percentage improvement or the improved scores of 5 sub-grouped symptoms after the 3-week treatment between C3435T genotypes and between G2677T/A genotypes. Multiple regression analyses including age, body weight, gender and drug concentration showed significant correlations between the percentage improvement and the improved scores of cognitive symptoms and C3435T genotypes. The present results suggest that the C3435T polymorphism is associated with some therapeutic response to bromperidol in schizophrenic patients, possibly by different drug concentration in the brain.
Adult↗
Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration.
The co-localization of amyloid beta (Abeta) and phosphorylated tau in astrocytes in a patient with corticobasal degeneration is described. At autopsy, the present case exhibited neuropathological findings compatible with those of corticobasal degeneration, including atrophy of the frontal and temporal lobes, neuronal loss and gliosis in the cortical and subcortical regions, and presence of cortical ballooned neurons and astrocytic plaques. Moreover, many senile plaques were found in the cerebral cortex. There were also clusters of Abeta-positive granules associated with astrocytic cytoplasm and processes in the subiculum and entorhinal cortex. In the entorhinal cortex, the Abeta-positive granules were occasionally co-localized with phosphorylated tau-positive fibrillary structures in the astrocytic cytoplasm. To our knowledge, this is the first demonstration of co-localization of Abeta and phosphorylated tau in astrocytes. This phenomenon implies that phagocytosis of Abeta coincides with production of phosphorylated tau in the same reactive astrocytes.
Amyloid beta-Peptides↗
Effects of zonisamide on neurotransmitter exocytosis associated with ryanodine receptors.
To clarify the antiepileptic and neuroprotective actions of zonisamide (ZNS), we determined acute effects of ZNS on exocytosis of GABA and glutamate associated with ryanodine-receptor (Ryr) in rat hippocampus using microdialysis. ZNS increased basal GABA release concentration-dependently without affecting basal glutamate release; however, K(+)-evoked glutamate and GABA releases were reduced by ZNS concentration-dependently. Inhibition of Ryr reduced K(+)-evoked GABA and glutamate releases without affecting their basal releases. Ryanodine affected GABA and glutamate releases biphasic concentration-dependently: lower concentration of ryanodine increased both basal and K(+)-evoked releases of GABA and glutamate, whereas higher concentration reduced them. The therapeutically relevant concentration of ZNS inhibited ryanodine-induced GABA and glutamate releases, and abolished the inflection point in concentration-response curve for ryanodine on neurotransmitter exocytosis. These data suggest that ZNS elevates seizure threshold via enhancement of GABAergic transmission during resting stage. ZNS inhibits propagation of epileptic hyperexcitability and Ryr-associated neuronal damage during neuronal hyperexcitable stage. These demonstrations indicate that the indirect inhibition of Ryr activities by ZNS during neuronal hyperexcitability appear to be involved in the mechanisms of action of antiepileptic and neuroprotective actions of ZNS.
Animals↗
Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.
The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.
Chromosomes, Human, Pair 1↗
Zonisamide at clinically relevant concentrations inhibits field EPSP but not presynaptic fiber volley in rat frontal cortex.
We investigated the effect of Zonisamide (ZNS), a newer anti-epileptic drug, on field potentials and neuropropagation in rat frontal cortex, with the aid of the 64-channel multi-electrode dish (MED64) system. The amplitude and propagation of field potentials were expressed dimensionally in the MED64 system. ZNS (3-100 microM) inhibited the amplitude and propagation of field excitatory postsynaptic potentials (fEPSP) in a concentration dependent manner. In contrast, ZNS could not suppress the amplitude and propagation of the presynaptic fiber volley (PrV) at clinically relevant concentrations (10-30 microM). Stimulating dependency with reduction fEPSP was seen in the presence of ZNS at clinically relevant concentrations, but not with PrV. The reduction of fEPSP amplitude was not accompanied by a change in paired-pulse facilitation. These data suggest that at clinically relevant concentrations of ZNS, the suppression of neuronal propagation is at least partially due to the postsynaptic mechanism, probably through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
Action Potentials↗
Time may be compressed in sound representation as replicated in sensory memory.
The flow of time in the real world may differ from the one in the neural representation of auditory scene stored in the sensory memory, because the encoded information is free from the rule of actual time. The sensory memory underlying the automatic discriminative system is reflected by the mismatch negativity (MMN). The time-wise image of preceding sounds is integrated into the sensory memory as a 160-170 ms epoch. We measured the mismatch field (MMNm) and the reaction time responding to the omitted segments incorporated into a complex sound. The main result was that the encoded period from early to late omitted segment was shorter than the actual one, suggesting that time may be compressed in the sound representation.
Acoustic Stimulation↗
Determination of fluvoxamine and its metabolite fluvoxamino acid by liquid-liquid extraction and column-switching high-performance liquid chromatography.
This study describes a new simultaneous determination of fluvoxamine and fluvoxamino acid by automated column-switching high-performance liquid chromatography. The test compounds were extracted from 1.5 ml of plasma using chloroform-toluene (15:85, v/v), and the extract was injected into a hydrophilic metaacrylate polymer column for clean-up and a C18 analytical column for separation. The mobile phase for separation consisted of phosphate buffer (0.02 M, pH 4.6), acetonitrile and perchloric acid (60%) (62.4:37.5:0.1, v/v/v) and was delivered at a flow rate of 0.6 ml/min. The peak was detected using a UV detector set at 254 nm. The method was validated for the concentration range 0.8-153.6 ng/ml for fluvoxamine and 0.6-115.2 ng/ml for fluvoxamino acid, and their good linearity (r > 0.998) were confirmed. Intra-day coefficient variations (CVs) for fluvoxamine and fluvoxamino acid were less than 6.6 and 6.0%, respectively. Inter-day CVs for corresponding compounds were 6.3 and 6.5%, respectively. Relative errors ranged from -18 to 9% and mean recoveries were 96-100%. The limit of quantification was 1.2 and 0.9 ng/ml for fluvoxamine and fluvoxamino acid, respectively. This method shows successful application for pharmacokinetic studies and therapeutic drug monitoring.
Amino Acids↗
Transient gamma-band response is dissociated from sensory memory as reflected by MMN.
The auditory gamma-band transient oscillatory response has been considered to reflect early cognitive processing and attention triggering, as has been suggested of the mismatch negativity (MMN). We examined whether the auditory gamma-band response was related to sensory memory as reflected by MMN. During the electroencephalogram (EEG) recordings, approximately 2000 click sounds were presented to nine healthy adult subjects with constant SOA of 120 or 170 ms in an ignored condition. At a probability of 10%, a click sound was randomly omitted from the stimulus sequence. EEG epochs responding to omitted clicks and to click sounds were averaged for analysis, respectively, and then those were convoluted by Gabor wavelet for the gamma-band response calculation. The MMN to a deviant omission in a sequence of click sounds was elicited with SOA of 120 ms which was shorter than the duration of temporal window of integration, whereas no MMN was elicited with SOA of 170 ms. In contrast with the MMN, the transient gamma-band response clearly commenced after the stimuli but not after the omissions, regardless whether SOA was short or long. The findings indicate that the brain process underlying the transient gamma-band response should be dissociated from the sensory memory function.
Adult↗
Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus.
Dynamic changes in intracellular free Ca(2+) concentration play a crucial role in various neural functions. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and the ryanodine (Ry) receptor (RyR) are involved in Ca(2+)-induced Ca(2+)-release (CICR). Recent studies have shown that type 3 IP3R is highly expressed in rat hippocampal neurons after kainic acid (KA)-induced seizures and that dantrolene, a RyR antagonist, reduces KA-induced neuronal cell death. We investigated the RyR-associated effects of CICR agents on basal and K(+)-evoked releases of GABA and glutamate in rat hippocampus and the changes in expression of mRNA for RyRs in mouse brain after KA-induced seizures. The stimulatory effect of Ry on releases of GABA and glutamate was concentration-dependent in a biphasic manner. The inflection point in concentration-response curves for Ry on GABA release was lower than that for glutamate in both basal and K(+)-evoked conditions, suggesting that hyperactivation of RyR-associated CICR produces the imbalance between GABAergic and glutamatergic transmission. Following KA-induced seizures, transient up-regulation of brain-type RyR mRNA was observed in the hippocampal CA3 region and striatum, and signals for c-Fos mRNA increased transiently in the hippocampus, dentate gyrus and deeper layers of the neocortex. Thereafter, some dead neurons with single-stranded DNA (ssDNA) immunoreactive fragmented nuclei appeared in these areas. These findings suggest that intracellular Ca(2+) release via the RyR might be one of the mechanisms involved in KA-induced neuronal cell death.
Animals↗
Thioridazine inhibits risperidone metabolism: a clinically relevant drug interaction.
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Adult↗
Dose-dependent interaction of paroxetine with risperidone in schizophrenic patients.
Augmentation with paroxetine (10-40 mg/d) for antipsychotic treatment may improve the negative symptoms in schizophrenic patients but involves a risk of drug-drug interaction. We studied the effects of paroxetine on plasma concentrations of risperidone and 9-hydroxyrisperidone and their clinical symptoms in risperidone-treated patients. Twelve schizophrenic inpatients with prevailingly negative symptoms receiving risperidone 4 mg/d were, in addition, treated with incremental doses of paroxetine for 12 weeks (10, 20, and 40 mg/d for 4 weeks each). Plasma concentrations of risperidone and 9-hydroxyrisperidone were quantified with liquid chromatography-mass spectrometry mass-mass spectrometry together with clinical assessments before and after each phase of the 3 paroxetine doses. Risperidone concentrations during coadministration of paroxetine 10, 20, and 40 mg/d were 3.8-fold (95% confidence interval, 3.2-5.8, P < 0.01), 7.1-fold (95% confidence interval, 5.3-16.5, P < 0.01), and 9.7-fold (95% confidence interval, 7.8-22.5, P < 0.01) higher than that before paroxetine coadministration, respectively. Active moiety (risperidone plus 9-hydroxyrisperidone) concentration was not increased during the paroxetine 10 mg/d (1.3-fold, not significant) or 20 mg/d (1.6-fold, not significant), but were significantly increased by 1.8-fold (95% confidence interval, 1.4-2.7, P < 0.05) during the paroxetine 40 mg/d. Significant improvement in negative symptoms was observed from 10 to 40 mg/d of paroxetine, whereas scores in extrapyramidal side effects during 20 and 40 mg/d of paroxetine were significantly higher than baseline score. This study indicates that paroxetine increases plasma risperidone concentration and active moiety concentration in a dose-dependent manner. Low-dose coadministration of paroxetine with risperidone may be safe and effective in the treatment of schizophrenic patients with negative symptoms.
Adult↗
Genetics of idiopathic epilepsies.
PURPOSE: To search for clues to molecular genetics of common idiopathic epilepsy syndromes. Genetic defects have been identified recently in certain inherited epilepsy syndromes in which the phenotypes are similar to those of common idiopathic epilepsies. METHODS: Mutations identified as the causes of inherited idiopathic epilepsies were reviewed. RESULTS: Mutations of the genes encoding two subunits of the neuronal nicotinic acetylcholine receptor were found in autosomal dominant nocturnal frontal lobe epilepsy. Mutations of two K(+)-channel genes were identified in benign familial neonatal convulsions. Mutations of the genes encoding several subunits of the voltage-gated Na(+)-channel and gamma-aminobutyric acid (GABA)(A) receptor also were identified as the underlying causes of various epilepsy syndromes, such as autosomal dominant epilepsy with febrile seizures plus, benign familial neonatal infantile seizures, and autosomal dominant juvenile myoclonic epilepsy. Mutations within the same gene may result in different epilepsy phenotypes. Thus, the Na(+) channel, GABA(A) receptor, and their auxiliaries may be involved in the pathogenesis of various types of epilepsy. Some forms of juvenile myoclonic epilepsy, idiopathic generalized epilepsy, and absence epilepsy may result from mutations of Ca(2+) channels. Mutations of the Cl(-) channel have been recently found to be associated with a certain type of epilepsy. The recent discovery that mutations of LGI1, a gene encoding a nonchannel molecule, are associated with autosomal partial epilepsy with auditory features may provide a new insight into our understanding of the genetics of idiopathic epilepsy. CONCLUSIONS: These findings suggest the involvement of brain channelopathies in the pathogenesis of certain types of idiopathic epilepsy.
Codon, Nonsense↗
Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A mutations in a Japanese cohort.
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Body Temperature↗
[Clinical pharmacogenetics in the treatment of schizophrenia].
Numerous investigations on metabolic enzymes, cytochrome P450 (CYP), have been conducted since 1990. In the psychiatric field, the focus has been on CYP2D6, which is a major enzyme involved in metabolism of antidepressants and antipsychotics. Poor metabolizers (deficit metabolizers) for CYP2D6 represent 7% among Caucasians, while they accouut for less than 1% of Asians. The frequency of a mutated allele for CYP2D6*10, which leads to the decrease in CYP2D6 activity, is 40% in Asians. It has been reported that steady-state plasma concentration of haloperidol in subjects with mutated alleles for CYP2D6 is significantly higher than that in subjects without mutated alleles. At the same time, steady-state plasma concentration of risperidone is very different between CYP2D6 genotypes. In addition, several studies suggest that better efficacy or higher scores of side effects are observed in the subjects with mutated alleles for CYP2D6. Recently receptor polymorphism has become a concern and association between clinical response and polymorphism of dopamine and serotonin has been reported. In the dopamine D2, subjects with -141C Ins allele in -141C Ins/Del polymorphism and subjects with A1 allele in Taq1A have a better response to dopamine antagonists. Association between Ser allele and typical antipsychotics and between Gly allele and atypical antipsychotics has been investigated. There are still no data indicating significant association between dopamine D1 and clinical response to antipsychotics. Clinical pharmacogenetical studies from both a pharmacokinetical and a pharmacogynamical point of view are required in order to introduce and practice individualized medicine in psychiatric field easily.
Alleles↗
[Psychophysiological basis of smells].
There has been an increase in the use of psychophysiological techniques, especially event-related potentials (ERPs) to evaluate the effects of odor on the central nervous system. In the study of ERPs related to odor, there are two main methods of the odor presentation: (1) to investigate the olfactory ERP (OERP) or chemosensory ERP (CSERP), that is to calculate electrophysiological responses to odor stimulation as a trigger; (2) to compare ERP of mental functioning during the odor exposed condition with that of no odor exposure. The amplitude of contingent negative variation (CNV) varies with the odorant being present, when the odor is presented as a trigger and when it is administrated during a task. It is suggested that CNV changes depend on not only the odorant but the anticipation, expectation and emotion of the subject. The latency of the N1 component becomes shorter with increasing concentrations of odors. The N1 amplitude does not depend on the odor concentration while the amplitude of the auditory N1 strongly depends on the stimulus intensity. There is only one report that the olfactory mismatch negativity (MMN) is present in the CSERP. On the other hand, auditory MMN is not affected by odor administration. In relation to the P3 component, rare odors evoked a larger amplitude in contrast to frequent odors, as well as P3 evoked by other modalities. These ERP studies with odors are expected to be applied to such clinical settings as the differentiation between the anosmic patients and normosmic persons, the functional evaluation of patients with brain tumors, the earlier detection of dementia, and the objective evaluation of aromatherapy.
Aromatherapy↗