Bando Chemical Industries (Japan)

BackgroundTo compare peramivir 300 mg single‐dose, peramivir 600 mg repeat‐dose, and oseltamivir effects on health‐related quality of life, including respiratory symptoms and general conditions, time to symptom alleviation, time to fever resolution, incidence of exacerbations, and virus titer, in influenza patients with chronic respiratory disease.MethodsWe report additional outcomes from a 2‐week, multicenter, randomized, open‐label study in Japan (UMIN000030118). Influenza patients with chronic respiratory disease received intravenous peramivir (300 mg single‐dose [n = 66], 600 mg repeat‐dose [600 mg/d of 2 consecutive days; n = 70]) or oral oseltamivir (75 mg twice daily, 5 days; n = 72). The principal endpoint of this analysis was change from baseline to Day 14 at each time point in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores.ResultsBoth peramivir regimens reduced total CAT score at Day 3 more than oseltamivir (peramivir 600 mg vs oseltamivir, P = .0032; peramivir 300 mg vs oseltamivir, P = .0203). Cough/phlegm CAT scores were most improved with peramivir 600 mg. Median time to alleviation of three respiratory symptoms was longer with peramivir 600 mg (68.9 hours) than with peramivir 300 mg (50.6 hours, hazard ratio [HR] 1.57; P = .0191) and shorter with peramivir 300 mg than oseltamivir (78.8 hours, HR 0.62; P = .0141). Alleviation of seven influenza symptoms and fever resolution was shortest with peramivir 300 mg.ConclusionsRapid improvement in CAT score, including cough, and shorter time to alleviation of respiratory symptoms associated with peramivir is of potential benefit to patients with chronic respiratory disease.

1H quantitative NMR (1H qNMR) is known as a powerful tool for determination of analytes without the need for their identical standards, which is eligible to a primary rate method. 1H qNMR has been already stipulated to an assay for purity determination in Japanese Pharmacopoeia (JP), and then this technique has been also applied in several fields such as pharmaceutical and food sciences. However, there is little information about the accuracy of 1H qNMR so that the further applications into other fields such as industrial chemistry could be constricted. In this study, in order to assess the reliability of 1H qNMR, we designed the round-robin test of 1H qNMR under the basis of the measurement conditions described in JP. 1,4-Bis(trimethylsilyl)benzene-d4 [1,4-BTMSB-d4, 99.9±0.6% (w/w)] and 3,5-bis(trifluoromethyl)benzoic acid [3,5-BTMFBA, 99.96±0.06% (w/w)], which are certified reference materials (CRMs), were adopted to analyte and qNMR reference standard respectively for the accurate evaluation in this test. Six NMR instruments in 5 institutions optimized to 1H qNMR conditions provided the purity 1,4-BTMSB-d4 within acceptable error range. This result represented that 1H qNMR has the capability to determine precisely the value of analyte in practical analytical field and to be set as official analytical method for purity determination or assay of concentration of organic compounds.

We have previously reported cases of patients who developed leukopenia and neutropenia caused by antipsychotic drug overdose.1 To our knowledge, there are no studies investigating the effect of chlorpromazine equivalent doses (CPZe) on white blood cell (WBC) count. Here we report that WBC counts were lower in patients receiving high CPZe, especially when receiving a combination of aripiprazole and quetiapine. Among patients who were hospitalized in the psychiatric department between January and December 2015, 83 patients had WBC counts below the reference range and had also been treated with antipsychotic drugs whose doses could be converted to CPZe. A total of 288 blood samples were collected from 83 patients and the WBC counts from these samples ranged from 1300/μL to 3490/μL. The WBC counts were <2000/μL (median: 1700/μL) in 36 samples (13%; nine patients). The WBC counts were in the range of 2000–2500/μL (median: 2300/μL), 2500–3000/μL (median: 2800/μL), and 3000–3500/μL (median: 3200/μL) in 45 samples (16%; 17 patients), 97 samples (34%; 39 patients), and 110 samples (38%; 67 patients), respectively. The median CPZe were 959 mg (200–1962 mg), 400 mg (76–1356 mg), 400 mg (50–2309 mg), and 300 mg (25–2206 mg) in patients with WBC counts of <2000/μL, 2000–2500/μL, 2500–3000/μL, and 3000–3500/μL, respectively. The antipsychotic drugs for which doses could be converted to CPZe in this study were aripiprazole (71 samples; 18 patients), quetiapine (89 samples; 25 patients), risperidone (59 samples; 36 patients), and olanzapine (101 samples; 30 patients). There was a weak but significant correlation between total CPZe and WBC count (r = −0.236, N = 288, Pearson's correlation coefficient, P = 0.001). In patients with WBC counts <2000/μL, the median CPZe of aripiprazole, quetiapine, risperidone, and olanzapine were 750 mg, 606 mg, 100 mg, and 400 mg, respectively. Among those with WBC counts in the range of 2000–2500/μL, the median doses for these drugs were 600 mg, 227 mg, 100 mg, and 400 mg, respectively. In patients with WBC counts in the range of 2500–3000/μL, the corresponding median doses were 600 mg, 455 mg, 400 mg, and 400 mg, respectively. Among patients with WBC counts in the range of 3000–3500/μL, the median doses were 450 mg, 152 mg, 200 mg, and 400 mg, respectively. For statistical analysis, we performed the Mann–Whitney U-test. For our study, we considered P < 0.05 to be statistically significant. In patients taking a combination of aripiprazole and quetiapine with combined CPZe > 1000 mg, the median WBC count was 1700/μL (19 samples; four patients). Samples of patients taking this combination with a combined CPZe < 1000 mg showed significantly higher median WBC count (2285/μL, 14 samples in four patients, Mann–Whitney U-test, P = 0.034) than those with CPZe > 1000 mg. We applied multiple regression analysis with a dependent variable of WBC count and independent variables of each drug (on or off) to determine the effect of each drug on WBC counts. Differences in WBC counts were only observed in patients who were treated with a combination of aripiprazole and quetiapine. This result supports our recommendation that routine blood tests should be conducted in hospitalized patients taking a combination of aripiprazole and quetiapine with CPZe > 1000 mg. These patients should be closely observed for signs of hematologic diseases to ensure early detection. The authors have no potential conflicts of interest to disclose.

Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose.

Because Rescue robot is used in various types of environment and running conditions, the robustness is essential for actuators used in the drive systems of robots. The new type actuator, we named Super-Robust HFD Electrical Actuator, has been developed. This actuator consists of the electric motor and the friction transmission type flat belt that protects the drive train from the impact overload. The fundamentals and mechanism of this actuator system is reported in this paper.

BackgroundThe successful establishment of human induced pluripotent stem cells (hiPSCs) has increased the possible applications of stem cell research in biology and medicine. In particular, hiPSCs are a promising source of cells for regenerative medicine and pharmacology. However, one of the major obstacles to such uses for hiPSCs is the risk of contamination from undefined pathogens in conventional culture conditions that use serum replacement and mouse embryonic fibroblasts as feeder cells.Methodology/Principal FindingsHere we report a simple method for generating or culturing hiPSCs under feeder- and serum-free defined culture conditions that we developed previously for human embryonic stem cells. The defined culture condition comprises a basal medium with a minimal number of defined components including five highly purified proteins and fibronectin as a substrate. First, hiPSCs, which were generated using Yamanaka's four factors and conventional undefined culture conditions, adapted to the defined culture conditions. These adapted cells retained the property of self renewal as evaluated morphologically, the expression of self-renewal marker proteins, standard growth rates, and pluripotency as evaluated by differentiation into derivatives of all three primary germ layers in vitro and in vivo (teratoma formation in immunodeficient mice). Moreover, levels of nonhuman N-glycolylneuraminic acid (Neu5Gc), which is a xenoantigenic indicator of pathogen contamination in human iPS cell cultures, were markedly decreased in hiPSCs cultured under the defined conditions. Second, we successfully generated hiPSCs using adult dermal fibroblast under the defined culture conditions from the reprogramming step. For a long therm culture, the generated cells also had the property of self renewal and pluripotency, they carried a normal karyotype, and they were Neu5Gc negative.Conclusion/SignificanceThis study suggested that generation or adaption culturing under defined culture conditions can eliminate the risk posed by undefined pathogens. This success in generating hiPSCs using adult fibroblast would be beneficial for clinical application.

When the charge sticks. A kinase activity screening system based on the aggregation of gold nanoparticles induced by cationic substrate peptides as coagulants has been constructed. The system can conduct and monitor kinase reactions under homogeneous conditions and has been successfully applied to the kinase assay of cell lysates. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2007/z700086_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.