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. 相似文献
The miscibility of poly(methyl methacrylate) (PMMA) and styrene-acrylonitrile random copolymers (SAN) blends was investigated on the basis of the Flory—Orwoll—Vrij equation of state theory. To obtain the equation of state parameters (P*, V*sp, T*: characteristic parameters), the pressure—volume—temperature (PVT) behaviour was measured for PMMA and a series of SANs with various acrylonitrile contents. The exchange energy parameter Xij was also calculated by fitting the theory to some phase diagrams of PMMA/SAN blends. The Flory—Huggins interaction parameter χ was separated into two contributions based on the equation of state theory for mixtures: the exchange energy term χinter and the free volume term χfree. Both the temperature and copolymer composition dependences of χinter and χfree were estimated by calculations using the equation of state parameters. There exists a region in which χinter is negative, leading to a miscibility window in PMMA/SAN blends. However, the immiscibility at high temperatures in the blends cannot be explained only by χinter; it is caused by the free volume contribution, χfree. The miscibility window behaviour in PMMA/SAN blends may be explained within the framework of the equation of state theory. 相似文献
The growth mechanism and morphology of Ge precipitates in an Al-Ge alloy was characterized by a combination of in-situ transmission electron microscopy, high-resolution transmission electron microscopy and three-dimensional electron tomography. Anisotropic growth of rod-shaped Ge precipitates was observed by in-situ transmission electron microscopy over different time periods, and faceting of the precipitates was clearly seen using high-resolution transmission electron microscopy and three-dimensional electron tomography. This anisotropic growth of rod-shaped Ge precipitates was enhanced by vacancy concentration as proposed previously, but also by surface diffusion as observed during the in-situ experiment. Furthermore, a variety of precipitate morphologies was identified by three-dimensional electron tomography. 相似文献
Fracture toughness of silicon crystals has been investigated using indentation methods, and their surface energies have been
calculated by molecular dynamics (MD). In order to determine the most preferential fracture plane at room temperature among
the crystallographic planes containing the 〈001〉, 〈110〉 and 〈111〉 directions, a conical indenter was forced into (001), (110)
and (111) silicon wafers at room temperature. Dominant {110}, {111} and {110} cracks were introduced from the indents on (001),
(011) and (111) wafers, respectively. Fracture occurs most easily along {110}, {111} and {110} planes among the crystallographic
planes containing the 〈001〉, 〈011〉 and 〈111〉 directions, respectively. A series of surface energies of those planes were calculated
by MD to confirm the orientation dependence of fracture toughness. The surface energy of the {110} plane is the minimum of
1.50 Jm−2 among planes containing the 〈001〉 and 〈111〉 directions, respectively, and that of the {111} plane is the minimum of 1.19
Jm−2 among the planes containing the 〈011〉 direction. Fracture toughness of those planes was also derived from the calculated
surface energies. It was shown that the KIC value of the {110} crack plane was the minimum among those for the planes containing the 〈001〉 and 〈111〉 directions, respectively,
and that KIC value of the {111} crack plane was the minimum among those for the planes containing the 〈011〉 direction. These results are
in good agreement with that obtained conical indentation. 相似文献
We describe a most straightforward synthetic method for preparing neurokinin‐1 (NK1) receptor antagonist derivatives by asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts using dinuclear iridium complexes with enantiopure diphosphine ligands, affording the corresponding chiral piperidines in high cis‐diastereoselectivity (>95:5) and moderately high enantioselectivity (up to 86%). Deprotection treatments afforded the NK‐1 receptor antagonist (+)‐CP‐99,994 (83% ee). In addition, we observed unique additive effects of 10‐camphorsulfonic acid in the asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts.
Dinuclear triply chloro‐bridged iridium(III) complexes bearing chiral diphosphine ligands catalyze the asymmetric hydrogenation of tosylamido‐substituted pyrazines to give the corresponding chiral tetrahydropyrazines with an amidine skeleton in high yield and with high enantioselectivity. Addition of N,N‐dimethylanilinium bromide enhanced the catalytic activity of the iridium complexes and also increased the enantioselectivity of the products by trapping the hydrogenated amine products with HBr from N,N‐dimethylanilinium bromide. The amidine skeleton of the products could be transformed to give chiral piperazinones and piperazines without loss of enantioselectivity.
Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use. 相似文献
The use of thrombolytic agents (plasminogen activators) in the early moments of ischemic stroke to achieve recanalization and potential neurologic improvement has been actively studied over the past 10 years. In the same period, endovascular techniques for cerebral revascularization have evolved significantly. Recent phase III studies, following angiography-based phase I and II studies of plasminogen activators in stroke, have described evidence of clinical benefit and contributors to morbidity (i.e., symptomatic hemorrhage) and mortality that limit the applicability of this approach. The limited formalized experience with percutaneous transluminal balloon angioplasty and stent placement in the carotid artery and cerebral circulation has given rise to concerns about the safety and appropriateness of the procedures in this territory. However, several prospective series support the feasibility of well-designed clinical trials. 相似文献
The role of the phase diagram for the Ga-As-S system in the selection of the starting diffusion source composition is discussed. The temperature dependence of the diffusion coefficient of sulfur in GaAs has been measured for various diffusion source compositions. For the 10:1 (GaS:As) source, the diffusion coefficient at 810° and 910°C are 1·9×10?14 and 0·9×10?12 cm2 sec?1 and for the 2:1 and 1:2 sources the coefficient at 810° and 910°C are 1·9×10?13 and 2·9×10?12 cm2 sec?1, respectively. The activation energy of the diffusion coefficient is found to be about 4·35 and 2·95 eV for the 10:1 source and for the 2:1 and 1:2 sources, respectively. These diffusion sources yield reproducible diffusion profiles without surface damage. The surface concentration of sulfur is estimated about 3×1018 cm?3 for the 10:1 source at 910°C diffusion. Breakdown voltage of the n+p junction prepared by these diffusion processes and SiN planar technology agrees extremely well with theoretical values. 相似文献