Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

Although antidepressants are generally effective in the treatment of major depressive disorder (MDD), it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine.     

Fracture Resistance Behavior of High‐Thermal‐Conductivity Silicon Nitride Ceramics

Silicon nitride ceramics were prepared from a high‐purity silicon powder doped with 2 mol% Y₂O₃ and 5 mol% MgO as sintering additives via a route of sintering of reaction‐bonded silicon nitride (SRBSN). The materials sintered at 1900°C for 3, 6, 12, and 24 h had thermal conductivities of 109, 125, 146, and 154 W/m/K, and four‐point bending strengths of 786, 676, 608, and 505 MPa, respectively. The fracture toughness values, determined by the single‐edge‐precracked‐beam (SEPB) method, were 8.4, 8.6, 9.7, and 10.7 MPa m^1/2 for the materials sintered for 3, 6, 12, and 24 h, respectively, which were similar to the results measured by the chevron‐notched‐beam (CNB) test method. The materials sintered for longer times (12 and 24 h) showed stronger R‐curve behaviors over longer range of crack extension, in comparison with the materials sintered for shorter times (3 and 6 h).     

Compression molding and melt‐spinning of the blends of poly(lactic acid) and poly(butylene succinate‐co‐adipate)

Poly(lactic acid) (PLA) is a biobased polymer made from biomass having high mechanical properties for engineering materials applications. However, PLA has certain limited properties such as its brittleness and low heat distortion temperature. Thus, the aim of this study is to improve toughness of PLA by blending with poly(butylene succinate‐co‐adipate) (PBSA), the biodegradable polymer having high toughness. Polymer blends of PLA and PBSA were prepared using a twin screw extruder. The melt rheology and the thermal property of the blends were examined. Further the blends were fabricated into compression molded parts and melt‐spun fiber and were subjected to tensile and impact tests. When the PBSA content was low, PBSA phase was finely dispersed in the PLA matrix. On the other hand, when the PBSA content was high, this minor phase dispersed as a large droplet. Mechanical properties of the compression molded parts were affected by the dispersion state of PBSA minor component in PLA matrix. Impact strength of the compression molded parts was also improved by the addition of soft PBSA. The improvement was pronounced when the PBSA phase was finely dispersed in PLA matrix. However, the mechanical property of the blend fibers was affected by the postdrawing condition as well as the PBSA content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41856.     

Structural Analysis of the Complex between Penta-EF-Hand ALG-2 Protein and Sec31A Peptide Reveals a Novel Target Recognition Mechanism of ALG-2

ALG-2, a 22-kDa penta-EF-hand protein, is involved in cell death, signal transduction, membrane trafficking, etc., by interacting with various proteins in mammalian cells in a Ca²⁺-dependent manner. Most known ALG-2-interacting proteins contain proline-rich regions in which either PPYPXnYP (type 1 motif) or PXPGF (type 2 motif) is commonly found. Previous X-ray crystal structural analysis of the complex between ALG-2 and an ALIX peptide revealed that the peptide binds to the two hydrophobic pockets. In the present study, we resolved the crystal structure of the complex between ALG-2 and a peptide of Sec31A (outer shell component of coat complex II, COPII; containing the type 2 motif) and found that the peptide binds to the third hydrophobic pocket (Pocket 3). While amino acid substitution of Phe⁸⁵, a Pocket 3 residue, with Ala abrogated the interaction with Sec31A, it did not affect the interaction with ALIX. On the other hand, amino acid substitution of Tyr¹⁸⁰, a Pocket 1 residue, with Ala caused loss of binding to ALIX, but maintained binding to Sec31A. We conclude that ALG-2 recognizes two types of motifs at different hydrophobic surfaces. Furthermore, based on the results of serial mutational analysis of the ALG-2-binding sites in Sec31A, the type 2 motif was newly defined.     

The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new tacrolimus formulation

We developed a water-in-oil-in-water (W/O/W)-type multiple emulsion of a new tacrolimus formulation. A potential approach to avoid the complications of systemic immunosuppression and simultaneously enhance immunosuppressive efficacy is to deliver immunosuppressive agents locally to the site of the target organs. The W/O/W emulsion is dispersed oil drops containing smaller water droplets that allow the delivery of drugs preferentially to the reticuloendothelial system (RES). Since the liver and the spleen are primary components of the RES, and the brain and the kidney have a poor RES, we hypothesized that a W/O/W emulsion of tacrolimus would prossess the pharmacokinetic benefits of local immunosuppression. We evaluated this hypothesis in a rat model. The tacrolimus levels of whole blood, the liver, spleen, brain, and kidney in rats given intravenous emulsions of tacrolimus (W/O/W group) were compared with a group administered tacrolimus alone (T group). There were no significant differences between the pharmacokinetic parameters of W/O/W group and T group based on whole blood data. However, the W/O/W group had significantly decreased tacrolimus levels in the brain and kidney, and significantly increased levels in the liver and spleen compared with the T group. These data suggest that the W/O/W emulsion is applicable as an intravenous drug carrier for local immunosuppression.     

Characterization of a Silk‐Resinified Compact Fabricated Using a Pulse‐Energizing Sintering Device

Pulse electric current sintering is used to prepare a compact from resinificated hydrous silk powder. Compacts with no remnant silk powders are formed with 20 wt% added water, 20–40 MPa molding pressure, and >353 K molding temperature. The latter two are much lower than those used for conventional hot pressing. No dependence on molding pressure and temperature are found in XRD or FT‐IR analysis, except for a compact molded at 473 K, for which silk fibroin decomposition is confirmed by DSC, EGA‐MS, and molecular weight measurements. The compact's three‐point bending strength depends on the molding temperature, except for the temperature at which silk fibroin decomposes. The maximum three‐point bending strength resembles that of general‐purpose epoxy resin and is much higher than that of PLA.

     

Shape memory properties of polypeptide hydrogels having hydrophobic alkyl side chains

Polypeptide hydrogels were prepared by cross-linking of hydrophobically-modified poly[N⁵-(2-hydroxyethyl) l-glutamine] having alkyl side chains –C_nH_2n+1. Chain length of the alkyl group was n = 8, 16, and 18, and their mole fractions in the polypeptide were varied in the range of 0.05–0.16. Shape memory ability of the prepared polypeptide hydrogels was investigated. After deformation at 60 °C, the hydrogel was cooled in order to fix the temporary deformed shape. It was found that crystallization of the alkyl side chains did not occur, and the fixation ability of the hydrogel at 0 °C was low. In the subsequent heating process, the deformed temporary shape spontaneously recovered to the original shape gradually with increasing temperature, in other words, the shape recovery ratio varied with depending on the recovery temperature. From these observations, it was proposed that the shape fixation of the polypeptide hydrogel was achieved by strong segregation of the hydrophobic alkyl chains at low temperature, and the shape recovery of the deformed hydrogel was accompanied by the gradual decrease of the segregation strength with the temperature increase.     

Thermodynamic stability of hydrogen+tetra-n-butyl phosphonium bromide mixed semi-clathrate hydrate

Three-phase equilibrium (pressure–temperature) relation of hydrate+aqueous+fluid phases for the hydrogen (H₂)+tetra-n-butyl phosphonium bromide (TBPB)+water ternary system was investigated in a temperature range of 281.90–295.94 K and a pressure range up to 170 MPa. The behavior of the three-phase coexisting curve indicates no structural transition in the present experimental region. The Raman spectra obtained in the H₂+TBPB mixed semi-clathrate hydrate crystal reveal that H₂ molecule occupies only small cage compartmentally and the TBPB molecule is encaged with a set of other large cages.