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The authors examined the effect of tandospirone on tardive dyskinesia (TD) and parkinsonian symptoms in an open study. Tandospirone did not bring about any favourable effect on TD, but it had a good effect on the parkinsonian symptoms.
Postmortem and PET studies indicate increased serotonin (5-HT)-5-HT1A receptor density in frontal and temporal cortices in schizophrenia, suggesting up-regulation secondary to diminished 5-HT1A-receptor stimulation. We previously conducted a series of pilot studies of the effects of the addition of tandospirone, a 5-HT1A partial agonist and azapirone derivative, to ongoing treatment with small to moderate doses of typical antipsychotic drugs, on cognitive function in patients with schizophrenia. The addition of tandospirone (30 mg/day), but not placebo, for 4 to 6 weeks was found to improve executive function and verbal learning and memory.
Methods and Results:
We have conducted a randomly-assigned placebo-controlled double-blind study to investigate the ability of the addition of buspirone to enhance cognitive function in subjects with schizophrenia treated with atypical antipsychotic drugs (AAPDs). Buspirone, 30 mg/day, outperformed placebo in improving the performance on a measure of attention/speeded motor performance and index of general cognitive function. The distinct cognition-enhancing ability of buspirone suggests its usefulness for patients who have large deficits in attention in spite of treatment with AAPDs.
The findings from these clinical studies indicate 5-HT1A receptors are a promising target for the management of psychotic symptoms and cognitive disturbances of schizophrenia. This concept has prompted the development of novel antipsychotic compounds with agonist actions at 5-HT1A receptors, e.g. F156063, SLV313, SSR181507, and bifeprunox. Evidence from basic studies with these drugs suggests an optimal balance of activity at 5-HT1A and dopamine-D2 receptors is required to gain cognitive benefits, which deserves further investigations.
The purpose of this study was to determine if perospirone, a second generation antipsychotic drug and partial agonist at serotonin-5-HT1A receptors, enhances electrophysiological activity, such as event-related potentials (ERPs), in frontal brain regions, as well as cognitive function in subjects with schizophrenia. P300 current source images were obtained by means of standardized low resolution brain electromagnetic tomography (sLORETA) before and after treatment with perospirone for 6 months. Perospirone significantly increased P300 current source density in the left superior frontal gyrus, and improved positive symptoms and performance on the script tasks, a measure of verbal social cognition. Perospirone also tended to enhance verbal learning memory in patients with schizophrenia. There was a significant correlation between the changes in P300 amplitudes on the left frontal lead and those in social cognition. These results suggest the changes in three-dimensional distribution of cortical activity, as demonstrated by sLORETA, may mediate some of the actions of antipsychotic drugs. the distinct cognition-enhancing profile of perospirone may be related to its actions on 5-HT1A receptors.
Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have previously been reported in schizophrenia. This study attempted to examine whether phenylalanine kinetics is altered in schizophrenia using the 13C-phenylalanine breath test (13C-PBT).
Subjects were 20 patients with schizophrenia and the same number of controls. 13C-phenylalanine was administered and then 13CO2 concentration in breath was monitored for 120 minutes. The Δ 13CO2 at each collecting time, the maximal Δ 13CO2 (Cmax), the time to reach Cmax (Tmax), the area under the curve of time course of Δ13CO2 (AUC), the cumulative recovery rate (CRR) at each collecting time of the 13C-PBT were calculated for each subject.
Body weight (BW) and diagnostic status were significant predictors for Cmax. BW, age and diagnostic status were significant predictors for AUC and CRR at 120 minutes (CRR0-120). A repeated measures ANCOVA controlling for age and BW revealed a different pattern of change in CRR over time between the patients and controls and that Δ13CO2 in schizophrenia were lower than that in healthy control at all sampling point during 120 min, with an overall significant differences between healthy control and schizophrenia. The ANCOVA controlling for age and BW, showed that Cmax, AUC and CRR0-120 were significantly lower in schizophrenics than in controls.
Our data indicate the different change of Δ13CO2 and CRR over time and the decreased Cmax, AUC and CRR0-120 of 13C-PBT in schizophrenia patients compared to healthy controls, suggesting the altered phenylalanine kinetics in schizophrenia.
It has been reported that cognitive functioning in major depressive disorder (MDD) can be affected by various factors, such as symptom severity, personality dimensions and stress hormone activity. However, the relative role of each is largely unknown.
Seventy-six non-remitted patients with MDD were recruited. Symptomatology was assessed by the 21-item version of the Hamilton Rating Scale for Depression and the Hopkins Symptom Checklist (HSCL). Personality was assessed by the Temperament and Character Inventory (TCI). Neurocognitive functions, including verbal and visual memory, delayed recall and attention/working memory were measured by the full version of the Wechsler Memory Scale-Revised. Neuroendocrine function was determined by the reactivity of cortisol and dehydroepiandrosterone-sulfate (DHEAS) to the combined dexamethasone/corticotropin releasing hormone test. To quantify cognitive impairments in patients, age-, sex- and education- matched 187 healthy controls were also recruited and administered the same neuropsychological test.
MDD patients performed significantly worse than controls on visual memory and delayed recall. A stepwise multiple regression analysis predicting performance of each cognitive domain from five HSCL dimensions, seven TCI dimensions and hormonal variables, controlling for age, gender and education, revealed that higher cooperativeness was the only significant predictor towards better verbal memory, that less somatization symptoms and lower self-directedness were significant predictors towards better visual memory, and that lower age, less anxiety symptoms and lower DHEAS levels after dexamethasone administration were significant predictors towards better delayed recall.
Besides symptomatology, some personality dimensions and neuroendocrine function may, at least partly independently, contribute to memory impairment in MDD.
Although maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are related to fetal growth, there is a paucity of data regarding how offspring sex affects the relationship between maternal BMI in underweight mothers (pre-pregnancy BMI <18.5 kg/m2) and size for gestational age at birth. The aim of this study was to investigate the effect of offspring sex on the relationships among maternal pre-pregnancy BMI, GWG and size for gestational age at birth in Japanese underweight mothers. Records of women with full-term pregnancies who underwent perinatal care at Kawasaki Municipal Hospital (Kawasaki, Japan) between January 2013 and December 2017 were retrospectively reviewed. The study cohort included underweight (n=566) and normal-weight women (18.5 kg/m2⩽pre-pregnancy BMI<25 kg/m2; n=2671). The incidence of small for gestational age (SGA) births in the underweight group was significantly higher than that in the normal-weight group (P<0.01). Additionally, SGA incidence in the underweight group was significantly higher than that in the normal-weight group (P<0.01) in female, but not male (P=0.30) neonates. In the women with female neonates, pre-pregnancy underweight was associated with a significantly increased probability of SGA (odds ratio [OR]: 1.80; P<0.01), but inadequate GWG was not (OR: 1.38; P=0.11). In contrast, in women with male neonates, inadequate GWG was associated with a significantly increased probability of SGA (OR: 1.53; P=0.03), but not with pre-pregnancy underweight (OR: 1.30; P=0.10). In conclusion, the present results suggest that pre-pregnancy underweight is associated with SGA in female offspring but not in male offspring.
It is thought that protoplanets formed in protoplanetary disks excite the orbital motion of the surrounding planetesimals, and the bow shocks caused by the highly excited planetesimals heat their icy component evaporating into gas. We have performed model calculations to study the evolution of molecular abundances of the evaporated icy component, which suggests sulfur-bearing molecules can be good tracers of icy planetesimal evaporation. Here we report the result of our ALMA observations of sulfur-bearing molecules towards protoplanetary disks. The lines were undetected but the obtained upper limits of the line fluxes and our model calculations give upper limits of the fractional abundances of x(H2S) < 10−11 and x(SO) < 10−10 in the outer disk. These results are consistent with the molecular abundances in comets in our Solar system.
The aim was to estimate the incidence of Mycobacterium tuberculosis (Mtb) infection in health-care workers (HCWs) in Japan. We repeated cross-sectional surveys of HCWs with QuantiFERON®-TB Gold (QFT-G) in 2003, 2005 and 2007 at a hospital with tuberculosis (TB) wards, and 311 HCWs who underwent QFT-G testing two or three times were included in the study. Five HCWs (1·8%) converted from negative to positive. Incidence of new TB infection was estimated to be 0·6/100 person-years by the CDC's definition. Thirteen positive persons (41%) reverted from positive to negative. Multivariable logistic regression analysis identified a significant association between QFT-G conversion and working in TB wards. The IFN-γ levels of all but two subjects with reverting or converting QFT-G results were close to the test's cut-off. The incidence of Mtb infection in HCWs at our hospital was higher than that estimated for the general population in Japan. Criteria for defining QFT-G conversion and reversion need further investigation considering the high proportion of reversion, as the incidence of infection would have changed if we had applied other definitions.
To investigate two clusters of diarrhoea cases observed in our geriatric hospital wards, the faecal specimens were analysed. Reversed passive latex agglutination assay revealed that 63·2% and 41·7% of the faecal specimens from each cluster were positive for Clostridium perfringens enterotoxin. PCR assay revealed that 71·4% and 68·8% of C. perfringens isolates from each cluster were positive for the enterotoxin gene (cpe). These observations suggested that both the clusters were outbreaks caused by enterotoxigenic C. perfringens. Subsequent pulsed-field gel electrophoresis analysis revealed that the two outbreaks were caused by different C. perfringens isolates. However, these outbreak isolates as well as other sporadic diarrhoea isolates shared a 75-kb plasmid on which the cpe gene and the tcp locus were located. The 75-kb plasmid had horizontally spread to various C. perfringens isolates and had caused outbreaks and sporadic infections. However, the site and time of the plasmid transfer are unclear.
Periodic axisymmetric vortex breakdown in a cylinder with a rotating end wall
When the fluid inside a completely filled cylinder is set in motion by the rotation of the bottom end wall, steady and unsteady axisymmetric vortex breakdown is possible. The onset of unsteadiness is via a Hopf bifurcation.
Figure 1 is a perspective view of the flow inside the cylinder where marker particles have been released from an elliptic ring concentric with the axis of symmetry near the top end wall. This periodic flow corresponds to a Reynolds number Re=2765 and cylinder aspect ratio H/R=2.5. Neighboring particles have been grouped to define a sheet of marker fluid and the local transparency of the sheet has been made proportional to its local stretching. The resultant dye sheet takes on an asymmetric shape, even though the flow is axisymmetric, due to the unsteadiness and the asymmetric release of marker particles.When the release is symmetric, as in Fig. 2, the dye sheet is also symmetric. These two figures are snapshots of the dye sheet after three periods of the oscillation (a period is approximately 36.3 rotations of the end wall). Figure 3 is a cross section of the dye sheet in Fig. 2 after 26 periods of the oscillation. Here only the marker particles are shown. They are colored according to their time of release, the oldest being blue, through green and yellow, and the most recently released being red. Comparison with Escudier's experiment shows very close agreement.
The particle equations of motion correspond to a Hamiltonian dynamical system and an appropriate.
“Stand-support sintering”, that is supporting the load of the sinter cake with bars or
plates attached to pallets, has been developed and applied practically to the sintering
machines in Kimitsu works, Nippon Steel. The stands start to support the load of the sinter
cake just after the top layer is melted and starts to solidify. Shrinkage is stopped
and the gas flow rate is increased when the stands start to support the load of the
sinter cake. It was found that sintering time was shortened and productivity was improved in
actual sintering machines.
Schistosoma species have traditionally been arranged in groups based on egg morphology, geographical origins, and the genus or family of snail intermediate host. One of these groups is the ‘S. indicum group’ comprising species from Asia that use pulmonate snails as intermediate hosts. DNA sequences were obtained from the four members of this group (S. indicum, S. spindale, S. nasale and S. incognitum) to provide information concerning their phylogenetic relationships with other Asian and African species and species groups. The sequences came from the second internal transcribed spacer (ITS2) of the ribosomal gene repeat, part of the 28S ribosomal RNA gene (28S), and part of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene. Tree analyses using both distance and parsimony methods showed the S. indicum group not to be monophyletic. Schistosoma indicum, S. spindale and S. nasale were clustered among African schistosomes, while S. incognitum was placed as sister to the African species (using ITS2 and 28S nucleotide sequences and CO1 amino acid sequences), or as sister to all other species of Schistosoma (CO1 nucleotide sequences). Based on the present molecular data, a scenario for the evolution of the S. indicum group is discussed.
Atomistic microstructures of long-period superstructures in Al-rich TiAl alloys were investigated by high-resolution transmission electron microscopy. The multi-slice image simulation revealed that Al-atoms in Ti-rich (002) layers of the superstructures are imaged as very bright dots under appropriate observing conditions. By enhancing the contrast of the very bright dots using an image processing technique, partially ordered long-period superstructures were clearly characterized. For the short-range order state, A4B, A2B and A3B type ordered-clusters are generated in the Ti-rich (002) layers. These ordered-clusters are in contact with each other, and form local microdomains of various superstructures, such as Al5Ti3, h-Al2Ti and so on. For the Al5Ti3 and h-Al2Ti ordered states, the ordered-clusters are tiled periodically to form the Al5Ti3 or h-Al2Ti domains and characteristic anti-phase boundary structures.
The status of Schistosoma sinensium (samples from Thailand and from Sichuan, China) relative to other species of the genus Schistosoma was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer 2 (ITS2). Trees inferred from these sequences place S. sinensium as sister to the S. japonicum group and suggest a basal position in the clade utilizing snails of the family Pomatiopsidae. The sequence differences between specimens of S. sinensium from China and Thailand are at least as great as between S. malayensis and S. mekongi. Schistosoma sinensium is probably best regarded as a species complex.
Los autores examinaron el efecto de la tandospirona sobre la discinesia tardía (DT) y los síntomas parkinsonianos en un estudio abierto. La tandospirona no produjo ningún efecto favorable sobre la DT, pero tuvo un buen efecto sobre los síntomas parkinsonianos.
We have investigated the cardiovascular and plasma noradrenaline response to surgical incision under sevoflurane anaesthesia and determined the end-tidal concentration of sevoflurane that blocks the adrenergic response or responses to surgical incision (MACBAR) and changes in mean arterial pressure (MAP) in response to surgical incision (MACBCR) in 50% of women. We randomly assigned 64 female patients, aged 20–49 years, to eight groups according to end-tidal sevoflurane concentration: 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0% and 8.5%. All patients received only sevoflurane anaesthesia. An increase of 10% or more from prestress (incision) values of MAP or plasma noradrenaline concentration was considered a positive response. The probability of no response to stress was analysed using logistic regression to obtain the probability of no response vs. end-tidal sevoflurane concentration and the best-fit curve from the maximum likelihood estimators of the model parameters. MACBAR (mean±SE) was 8.0±0.2%, MACBCR was 7.9±0.2%. However, such high doses of sevoflurane cannot be used clinically because of their high toxicity. It may be preferable to combine sevoflurane with other anaesthetics to reduce haemodynamic responses to strong stimulation.
Electrochemistry of a nickel electrode in propylene carbonate [PC] containing LiClO4, LiCF3SO3, LiPF6 was studied through a micro electrode (φ =25 μ m) techniques in the wide potential range between +4.5 and -0.2 V vs. Li/Li+. Common pronounced peaks were observed in the potential range positive to lithium electrodeposition on nickel in all electrolyte solutions examined. Thus, these peaks can be attributed to reactions related to Li+ or commonly contained contaminants such as water and acids. In particular, the peak which appeared at the most negative potential seemed to be underpotential deposition (UPD) of lithium.
To prove this hypothesis a nickel electrode in highly dried PC (water content : 3 – 8 ppm) intentionally contaminated with a small amount of water and CF3COOH was examined via cyclic voltammetry. Changing the content of water and acid (and its ratio) in PC resulted in a variety of voltammograms and one of them was identical to the one observed in PC containing lithium electrolytes. These facts preclude the existence of UPD of lithium on nickel in the electrolyte solutions. Instead, the existence of NiOH on nickel and its redox reaction mechanism have been postulated. The mechanism is consistent with the experimental facts : a nickel electrode passivates in PC with a small amount of water, and a small amount of acid, CF3COOH, can prevent passivation. The vicinity of the electrode surface may be exposed to an alkaline atmosphere owing to the reduction product of water. This seems to be the cause of troubles we run into with the electrodes at cathodic potentials