Tardive Dyskinesia in Relation to Estimated Dopamine D2 Receptor Occupancy in Patients with Schizophrenia: Analysis of the CATIE data

Objective The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods The dataset from 218 subjects (risperidone, N=78; olanzapine, N=100; ziprasidone, N=40) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥6 months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥2 at endpoint and those with a score of zero, using the Mann-Whitney U test. Results Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N=23) than those who did not (N=195) (71.7±14.4% vs. 64.3±19.3%, p<0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.4±8.7% vs. 72.1±9.9%, p=0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Conclusion Greater dopamine D2 receptor blockade with antipsychotics at trough might increase the risk of tardive involuntary movements although this finding needs to be replicated in larger trials

Hydrogen-bond-assisted isotactic-specific radical polymerization of N-vinyl-2-pyrrolidone with tartrate additives in toluene at low temperatures : high-resolution 1H NMR analysis

A diethyl L-tartrate (L-EtTar)-assisted radical polymerization of N-vinyl-2-pyrrolidone has been developed as the first reported example of the synthesis of isotactic-rich poly(N-vinyl-2-pyrrolidone) (PVP). The addition of L-EtTar in toluene at temperatures of –40°C and lower led to a significant increase in the polymer yield by one order of magnitude compared with the reaction in the absence of L-EtTar. Decreasing the polymerization temperature led to increases in the isotacticity of the PVP, with the mm triad reaching 66.4% at −93 °C. 1H NMR measurement at 920 MHz was conducted to establish a reliable strategy for quantifying the triad tacticities. High-temperature NMR measurements at 250 °C were performed using a specially-designed NMR probe, which led to dramatic narrowing of the 1H line width

Catalytic performance and QXAFS analysis of Ni catalysts modified with Pd for oxidative steam reforming of methane

Pd–Ni bimetallic catalysts prepared by co-impregnation and sequential impregnation methods were compared in the catalytic performance in oxidative steam reforming of methane. The sequential impregnation was more effective to the suppression of hot spot formation. According to the structural analysis by in situ quick-scanning X-ray absorption fine structure (QXAFS) during the temperature programmed reduction, the sequential impregnation method gave the bimetallic particles with higher Pd surface composition because of the low possibility of the Pd–Ni bond formation. Higher surface composition of Pd with higher reducibility than Ni is connected to the enhancement of the catalyst reducibility and the suppression of the hot spot formation

The Dynamical State of the Serpens South Filamentary Infrared Dark Cloud

We present the results of N_2H^+ (J = 1-0) observations toward Serpens South, the nearest cluster-forming, infrared dark cloud. The physical quantities are derived by fitting the hyperfine structure of N_2H^+. The Herschel and 1.1 mm continuum maps show that a parsec-scale filament fragments into three clumps with radii of 0.1-0.2 pc and masses of 40-230 M_☉. We find that the clumps contain smaller-scale (~0.04 pc) structures, i.e., dense cores. We identify 70 cores by applying CLUMPFIND to the N_2H^+ data cube. In the central cluster-forming clump, the excitation temperature and line-width tend to be large, presumably due to protostellar outflow feedback and stellar radiation. However, for all the clumps, the virial ratios are evaluated to be 0.1-0.3, indicating that the internal motions play only a minor role in the clump support. The clumps exhibit no free fall but exhibit low-velocity infall, and thus the clumps should be supported by additional forces. The most promising force is the globally ordered magnetic field observed toward this region. We propose that the Serpens South filament was close to magnetically critical and ambipolar diffusion triggered the cluster formation. We find that the northern clump, which shows no active star formation, has a mass and radius comparable to the central cluster-forming clump and is therefore a likely candidate of a pre-protocluster clump. The initial condition for cluster formation is likely to be a magnetically supported clump of cold, quiescent gas. This appears to contradict the accretion-driven turbulence scenario, for which the turbulence in the clumps is maintained by the accretion flow