Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses

Clozapine is the first atypical antipsychotic, and improves positive and negative symptoms of many patients with schizophrenia resistant to treatment with other antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but is more often associated with seizures. A large number of studies have been conducted to elucidate pharmacological profiles of clozapine and its major active metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number of electrophysiological studies examining their effects on synaptic transmission. In this study, we examined effects of clozapine and NDMC on synaptic transmission by measuring inhibitory and excitatory postsynaptic currents in rat cultured hippocampal neurons. We found that clozapine and NDMC have qualitatively similar actions. They depressed the inhibitory transmission at 1-30 μM, and the excitatory transmission at 30 μM, the former being much more sensitive. The depression of IPSCs by 30 μM of these drugs was associated with an increase in the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs, but less sensitive than IPSCs. The AMPA-induced currents were slightly potentiated by these drugs at 30 μM. At 30 μM, clozapine and NDMC slightly suppressed Ca2+ and Na+ channels. These results strongly suggest that clozapine and NMDC depress the inhibitory synaptic transmission mainly by antagonizing postsynaptic GABAA receptors, but at higher concentrations additionally by acting on presynaptic site, possibly in part through inhibition of presynaptic Ca2+ and Na+ channels. Preferential depression of inhibitory synaptic transmission by clozapine and NDMC might contribute to therapeutic actions and/or side-effects of clozapine. © 2011 Elsevier B.V. All rights reserved

The role of eating together among university students

論文 (Article

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

Oral Microbiome in Four Female Centenarians

The oral microbiome of healthy older adults has valuable information about a healthy microbiome. In this study, we collected and analyzed the oral microbiome of denture plaque and tongue coating samples from four female centenarians. After DNA extraction and purification, pyrosequencing of the V3–V4 hypervariable regions of the 16S rRNA was carried out. The bacterial taxonomy for each lead was assigned based on a search of the EzBioCloud 16S database. We obtained a total of 199,723 valid, quality-controlled reads for denture plaque and 210,750 reads for tongue coating. The reads were assigned 407 operational taxonomic units with a 97% identity cutoff. Twenty-nine species were detected in both denture plaque and tongue coatings from all subjects. Firmicutes was the most abundant phylum; the Streptococcus salivarius group was the most abundant species in both the denture plaque and tongue coatings; and the Fusobacterium nucleatum group was detected in all subjects. In the bacterial profile, species formed clusters composed of bacteria with a wide range of prevalence and abundance, not dependent on phyla; each cluster may have specific species that could be candidates for a core microbiome. Firmicutes and Veillonella were abundant phyla on both plaque and tongue coatings of centenarians

Impact of the Serum Level of Albumin and Self-Assessed Chewing Ability on Mortality, QOL, and ADLs for Community-Dwelling Older Adults at the Age of 85: A 15 Year Follow up Study

Quality of life (QOL) and mortality are true endpoints of epidemiological or medical research, especially for community-dwelling older adults. Nutritional status and activities of daily living (ADLs) are associated with QOL and mortality. Good oral health status supports a good nutritional status. The aim of this study was to elucidate the complex structure of these important health-related factors. We surveyed 354 healthy older adults at the age of 85. Nutritional status was evaluated by the serum level of albumin. QOL, ADLs, self-assessed chewing ability, serum albumin level, and mortality during the 15 year follow up period were analyzed. Self-assessed chewing ability was associated with QOL and ADLs. Self-assessed chewing ability for slight-hard foods was associated with mortality in men. However, it was not associated with the serum albumin level. The serum albumin level was associated with mortality in women. These results indicate that maintaining good oral function is not enough. Nutritional instruction in accordance with oral function is indispensable for health promotion in older adults. When planning health promotion strategies for older adults, different strategies are needed for men and women