The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine

Although recent evidence suggests that certain beta-lactam antibiotics are absorbed via a specific transport mechanism, its nature is unclear. To confirm whether peptide transport in the rat can be largely ascribed to the intestinal oligopeptide transporter PepT1, the transporter has been functionally characterized and its significance in the intestinal absorption of beta-lactam antibiotics was evaluated. For evaluation of transport activity complementary RNA (cRNA) of rat PepT1 was synthesized in-vitro and expressed in Xenopus laevis oocytes. cRNA induced uptake of several beta-lactam antibiotics and the dipeptide [14C]glycylsarcosine; this was specifically inhibited by various dipeptides and tripeptides but not by their constituent amino acids or by tetra- or pentapeptides. The transport activity of PepT1 for beta-lactam antibiotics correlated well with their in-vivo intestinal transport and absorption. Furthermore, mutual inhibitory effects on uptake were observed between glyclsarcosine and beta-lactam antibiotics. Hybrid depletion of the functional expression of rat PepT1 in oocytes injected with rat intestinal epithelial total mRNA was studied using an antisense oligonucleotide corresponding to the 5'-coding region of PepT1. In oocytes injected with rat mRNA pre-hybridized with the antisense oligonucleotide against rat PepT1, the uptake of [14C]glycylsarcosine was almost completely abolished, whereas its uptake was not influenced by a sense oligonucleotide for the same region of PepT1. Similarly, the uptake of beta-lactam antibiotics was also reduced by the antisense oligonucleotide against rat PepT1. These results demonstrate that the intestinal proton-coupled oligopeptide transporter PepT1 plays a predominant role in the carrier-mediated intestinal absorption of beta-lactam antibiotics and native oligopeptides in the rat.     

Influence of additional elements (Mo,Nb, Ta and B) on the mechanical properties of high-manganese dual-phase steels

The influence of a small amount of alloying elements such as molybdenum, niobium, tantalum and boron to the 3 wt% Mn ferritic dual-phase steels was examined. These elements give a microstructure in which the fine martensite phase is well dispersed in the ferrite matrix, which 4leads to a remarkable reinforcement effect on mechanical properties. It is possible to obtain a tensile strength, _R, approaching 700 M Pa with a fracture elongation,A _R, of more than 40%, or _R 1000 MPa withA _R = ± 20% with relatively simple heat treatment.[/p]     

Protective effect of phytic acid hydrolysis products on iron-induced lipid peroxidation of liposomal membranes

Beneficial effects of dietary phytic acid (myo-inositol hexaphosphate; IP₆) have often been explained by its strong iron ion-chelating ability, which possibly suppresses iron ion-induced oxidative damage in the gastrointestinal tract. Because phytic acid is hydrolyzed during digestion, this work aimed to know whether its hydrolysis products (IP_2′ IP_3′, IP_4′ and IP₅) could still prevent iron ion-induced lipid peroxidation. Studies using liposomal membranes demonstrated that hydrolysis products containing three or more phosphate groups are able to inhibit iron ion-induced lipid peroxidation although their effectiveness decreased with dephosphorylation. Similarly, they also prevented iron ion-induced decomposition of phosphatidylcholine hydroperoxide. These results demonstrate that intermediate products of phytic acid hydrolysis still possess iron ion-chelating ability, and thus they can probably prevent iron ion-induced lipid peroxidation in biological systems.     

Reduction of fatty acid hydroperoxides by human parotid saliva

Arachidonic acid hydroperoxide (15-hydroperoxyeicosatetraenoic acid; 15-HPETE) was introduced into human parotid saliva and incubated at 37°C. Straight phase high-performance liquid chromatography analysis of the reaction mixture showed that 15-HPETE was detoxified to its reduced form, 15-hydroxyeicosatetraenoic acid, in the presence of glutathione. Therefore, it is concluded that human parotid saliva possesses fatty acid hydroperoxide-reducing ability. However, its effectiveness was found to be lower than that of blood plasma.     

Fabrication of Bulk β-FeSi2 Crystal With ThreeDimensional Alignment by an Oscillating Magnetic Field

It has been reported that an anisotropic magnetic field could produce the three-dimensional alignment of fine single-crystal particles with the orthorhombic crystal structure.However,the three-dimensional alignment was achieved only in suspensions.Fabrication of bulk"single"materials that have the three-dimensional alignment of grains has been desired.This study proposes a procedure for the fabrication,which consists of slip casting under an oscillating magnetic field and sintering.Optimization of casting and sintering conditions achieved the three-dimensionally aligned bulkβ-FeSi₂.     

Synthesis of New Pb-Based 1222 Cuprates Containing Phosphorus, (Pb0.75P0.25)Sr2(RE2–x–y Ce x Sr y )Cu2O z (RE = Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, Yb, and Y)

New Pb-based 1222 cuprates containing phosphorus have been synthesized in the (Pb_0.75P_0.25)Sr₂- (RE_2–x–y Ce _x Sr _y )Cu₂O _z (RE = Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, Yb, and Y) systems. The almost-single phase samples are obtained for 0.5≤x≤1.0 and y=0.1 in the cases of RE = Nd, Dy, Ho, Er, Tm, Yb and Y, while for 0.3≤x≤1.0 and y=0.1 in the cases of RE = Sm, Eu and Gd. The samples crystallize in a tetragonal lattice, the lattice parameters a and c are decreasing with the decrease of the ionic radius of the RE element. Even after annealing under 143 atm O₂ atmosphere at 400 °C, almost all the samples with the common values x=0.5 and y=0.1 are semiconductors with a transport process followed by three-dimensional variable range hopping. However, the samples of RE = Sm, Eu and Gd, which are of almost single 1222 phase, even for x=0.3 and y=0.1, show superconductivity with the onsets at about 25 K, 20 K and 22 K, respectively. Through this study, we find very important procedure for discovery of new superconducting 1222 compound.     

Impact of Dynamic Interlayer Interactions on Thermal Conductivity of Ca3Co4O9

The phonon thermal conductivity of misfit-layered Ca₃Co₄O₉ has been calculated by perturbed molecular dynamics using a classical force field. Detailed numerical analyses reveal that, in spite of its smaller cross-sectional area, the CoO₂ layer transports more heat than the thicker rock salt (RS) layer, although its local thermal conduction is more suppressed than in another layered cobaltite, Na _x CoO₂. The origins of these differences have been elucidated through careful examination of the atomic arrangements in each layer. Since thermal conduction in the RS layer can be reduced without deteriorating electronic properties for which the CoO₂ layer is responsible, it is suggested that the RS layer should be modified to further suppress the overall in-plane thermal conductivity. Computational experiments with increasing number of Ca–O planes in the RS layer showed the opposite trend to what can be predicted based on the misfit between two dissimilar layers. Further analyses to reveal the origin of these unexpected results provide yet another strategy to further decrease the thermal conductivity, namely to control the dynamic interference between atoms across the interface between two layers.     

Production of Gentiobiose from Hydrothermally Treated Aureobasidium pullulans β-1,3-1,6-Glucan

We report production of the functional disaccharide gentiobiose β-D-Glcp-(1→6)-D-Glc by a hydrolysis reaction of hydrothermally treated Aureobasidium pullulans β-1,3-1,6-glucan as the substrate and Kitalase as the enzyme. Gentiobiose was produced over the pH range 4−6 and the concentration of gentiobiose produced decreased above pH 7. The maximum value of gentiobiose production was unaffected by the enzyme concentration. The maximum concentration of gentiobiose produced was dependent on the substrate concentration whereas the maximum ratio of gentiobiose to glucose was not. The production of gentiobiose from yeast β-1,3-1,6-glucan was lower than that from A. pullulans β-1,3-1,6-glucan.     

Immunomodulatory Properties and Osteogenic Activity of Polyetheretherketone Coated with Titanate Nanonetwork Structures

Polyetheretherketone (PEEK) is a potential substitute for conventional metallic biomedical implants owing to its superior mechanical and chemical properties, as well as biocompatibility. However, its inherent bio-inertness and poor osseointegration limit its use in clinical applications. Herein, thin titanium films were deposited on the PEEK substrate by plasma sputtering, and porous nanonetwork structures were incorporated on the PEEK surface by alkali treatment (PEEK-TNS). Changes in the physical and chemical characteristics of the PEEK surface were analyzed to establish the interactions with cell behaviors. The osteoimmunomodulatory properties were evaluated using macrophage cells and osteoblast lineage cells. The functionalized nanostructured surface of PEEK-TNS effectively promoted initial cell adhesion and proliferation, suppressed inflammatory responses, and induced macrophages to anti-inflammatory M2 polarization. Compared with PEEK, PEEK-TNS provided a more beneficial osteoimmune environment, including increased levels of osteogenic, angiogenic, and fibrogenic gene expression, and balanced osteoclast activities. Furthermore, the crosstalk between macrophages and osteoblast cells showed that PEEK-TNS could provide favorable osteoimmunodulatory environment for bone regeneration. PEEK-TNS exhibited high osteogenic activity, as indicated by alkaline phosphatase activity, osteogenic factor production, and the osteogenesis/osteoclastogenesis-related gene expression of osteoblasts. The study establishes that the fabrication of titanate nanonetwork structures on PEEK surfaces could extract an adequate immune response and favorable osteogenesis for functional bone regeneration. Furthermore, it indicates the potential of PEEK-TNS in implant applications.