Response Surface Methodology Study on Magnetite Nanoparticle Formation under Hydrothermal Conditions

In a hydrothermal preparation of crystalline magnetite (Fe3O4) nanoparticles, the influence of the experimental parameters (initial molar ratio of ferrous/ferric ions, initial concentration of ferrous ions, and heating time), and their interactions, on the particle formation was studied using response surface methodology (RSM), based on a statistical design of experiments (DOE). As indices indicating particle formation and crystallization, the variation in the particle diameter and crystallite size with the synthesis conditions was examined. The crystallite size was greatly affected by both the initial ferrous/ferric ion molar ratio and the heating time, whereas the particle diameter strongly depended on the heating time, and on the interaction between the initial ferrous/ferric ion molar ratio and the initial concentration of ferrous ions. The results from a statistical analysis suggest that the polycrystalline Fe3O4 nanoparticles form via crystal growth and/or thermal aggregation, after nucleation during hydrothermal treatment

Circulating Malondialdehyde-Modified LDL-Related Variables and Coronary Artery Stenosis in Asymptomatic Patients with Type 2 Diabetes

Aims. To elucidate the levels of malondialdehyde-modified LDL (MDA-LDL)-related variables for predicting coronary artery stenosis (CAS) by coronary CT angiography (CCTA) in asymptomatic patients with type 2 diabetes (T2DM). Methods. Enrolled were 36 Japanese patients with T2DM who underwent CCTA and in whom MDA-LDL levels were measured. Definition of CAS was luminal narrowing of ≥50%. Trends through tertiles of each MDA-LDL-related variable were analyzed with a general linear model. The ability of each MDA-LDL-related variable to predict CAS was compared to areas under the curve (AUCs) in receiver operating characteristic curve (ROC) analysis. Results. Seventeen patients had CAS. Each MDA-LDL-related variable was an independent predictor of CAS (P=0.039 for MDALDL, P=0.013 for MDA-LDL/LDL-C, P=0.047 for MDA-LDL/HDL-C, and P=0.013 for (MDA-LDL/LDL-C)/HDL-C). AUCs of MDA-LDL, MDA-LDL/LDL-C, MDA-LDL/HDL-C, and (MDA-LDL/LDL-C)/HDL-C were 0.675 (95% CI 0.496–0.854), 0.765 (0.602–0.927), 0.752 (0.592–0.913), and 0.799 (0.643–0.955), respectively, for predicting CAS. Trends throughout the tertiles showed significant associations between MDA-LDL/LDL-C, MDA-LDL/HDL-C, or (MDALDL/LDL-C)/HDL-C and CAS (P=0.003 for MDA-LDL/LDL-C, P=0.042 for MDA-LDL/HDL-C, and P=0.001 for (MDA-LDL/LDL-C)/HDL-C). Conclusions. Data suggest that measurements of MDA-LDL/LDL-C, MDA-LDL/HDLC, and (MDA-LDL/LDL-C)/HDL-C are useful for predicting CAS

The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis

Protein ubiquitination is a post-translational protein modification that regulates many biological conditions [1], [2], [3], [4]. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1 [5], [6]. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12mt/mt) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16 [7], [8], [9], [10]. In contrast, Trip12mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development

Removal of a catheter mount and heat-and-moisture exchanger improves hypercapnia in patients with acute respiratory distress syndrome

To avoid ventilator-associated lung injury in acute respiratory distress syndrome (ARDS) treatment, respiratory management should be performed at a low tidal volume of 6 to 8 mL/kg and plateau pressure of ≤30 cmH2O. However, such lung-protective ventilation often results in hypercapnia, which is a risk factor for poor outcomes. The purpose of this study was to retrospectively evaluate the effectiveness and safety of the removal of a catheter mount (CM) and using heated humidifiers (HH) instead of a heat-and-moisture exchanger (HME) for reducing the mechanical dead space created by the CM and HME, which may improve hypercapnia in patients with ARDS.This retrospective observational study included adult patients with ARDS, who developed hypercapnia (PaCO2 > 45 mm Hg) during mechanical ventilation, with target tidal volumes between 6 and 8 mL/kg and a plateau pressure of ≤30 cmH2O, and underwent stepwise removal of CM and HME (replaced with HH). The PaCO2 values were measured at 3 points: ventilator circuit with CM and HME (CM + HME) use, with HME (HME), and with HH (HH), and the overall number of accidental extubations was evaluated. Ventilator values (tidal volume, respiratory rate, minutes volume) were evaluated at the same points.A total of 21 patients with mild-to-moderate ARDS who were treated under deep sedation were included. The values of PaCO2 at HME (52.7 ± 7.4 mm Hg, P < .0001) and HH (46.3 ± 6.8 mm Hg, P < .0001) were significantly lower than those at CM + HME (55.9 ± 7.9 mm Hg). Measured ventilator values were similar at CM + HME, HME, and HH. There were no cases of reintubation due to accidental extubation after the removal of CM.The removal of CM and HME reduced PaCO2 values without changing the ventilator settings in deeply sedated patients with mild-to-moderate ARDS on lung-protective ventilation. Caution should be exercised, as the removal of a CM may result in circuit disconnection or accidental extubation. Nevertheless, this intervention may improve hypercapnia and promote lung-protective ventilation

Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP