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.     

Infrequent mutation of the H-cadherin gene on chromosome 16q24 in human breast cancers

To investigate the molecular basis of altered expression of the H-cadherin gene, we used polymerase chain reaction-single strand conformation polymorphism and DNA sequencing to examine the H-cadherin gene in 48 primary breast cancers in which loss of the long arm of chromosome 16 had been detected. We identified no mutations other than somatic 5-bp deletion within the coding region in a single tumor. The very low frequency of mutation found in these experiments suggests that H-cadherin is usually not a primary target for carcinogenesis in human breast cancers, and that reduction of its expression is likely to be a consequence of some other genetic event(s).     

A process model for active brazing of ceramics: Part II Optimization of brazing conditions and joint properties

In the present investigation, the process model developed in Part I has been applied to evaluate the microstructure and strength evolution during active brazing of ceramics. As a starting point, reaction-layer growth is assumed to occur isothermally with no restrictions in the supply of reactive element. Different kinds of diagrams are then constructed to show how specific process variables (e.g. the heating and cooling period, the limiting layer thickness, and the diffusion mechanism) affect the growth kinetics. It is concluded that the key to improved joint properties lies in control of the reaction-layer thickness through optimization of the brazing conditions, and an illustration of this is given. This revised version was published online in November 2006 with corrections to the Cover Date.     

Effect of dynamic strain ageing on the tensile properties of a modified 9Cr–1Mo steel

Tensile testing of a modified 9Cr–1Mo steel in two microstructural conditions (710T– normalized at 1100°C, tempered at 710°C, and 550T – normalized at 1100°C tempered at 550°C) in the temperature range 25–450°C, under strain rates of 2.3×10-5–2.3×10-3s-1, exhibited serrated flow curves, with serrations appearing almost at the onset of deformation and disappearing before ultimate strengths were attained. The serrated flow curves (characteristics of dynamic strain ageing) were accompanied by increased ultimate strengths, loss of ductility and negative strain-rate sensitivity, relative to the ambient temperature properties. However, the increase in ultimate strength and the reduction in ductility were much larger for 710T specimens, as compared to 550T ones. In the dynamic strain ageing regime, the work-hardenability of 710T specimens increased rapidly while that of 550T specimens remained practically unaffected. Based on the microstructural consideration and the observed activation energy of 45 kJ mol-1, it is proposed that serrations are initiated by a nitrogen atmosphere formation on the waiting dislocations by a pipe diffusion mechanism, and they disappear by diffusion to the precipitate sinks during deformation. Because the fine alloy carbide precipitates in 550T specimens are more effective sinks than those of 710T ones, they can cause much faster depletion of the atmosphere, resulting in a much smaller effect of dynamic strain ageing on the tensile properties of 550T specimens.     

A construction of codes with exponential error bounds on arbitrarydiscrete memoryless channels

This correspondence proposes an explicit construction of codes achieving capacity for arbitrary discrete memoryless channels. The proposed code is obtained by concatenating variable inner codes and an algebraic geometry code. Further, we clarify that the proposed code achieves the error exponent obtained by Forney for concatenated codes     

Determination of a new podophyllotoxin derivative, TOP-53, and its metabolite in rat plasma and urine by high-performance liquid chromatography with electrochemical detection

A high-performance liquid chromatographic method was developed for the determination of a new podophyllotoxin derivative, TOP-53 (I), and TOP-53 glucuronide (II) as its major metabolite in rat plasma and urine. For the analysis of I, the sample was chromatographed on a reversed-phase C18 column with electrochemical detection after consecutive two-step liquid-liquid extractions. Compound II was determined as I after enzymatic hydrolysis of II. This method was validated sufficiently with respect to specificity, accuracy, and precision. The limits of quantitation for both I and II were 2 ng/ml in plasma and 10 ng/ml in urine. The method is thus useful for the pharmacokinetic study of I.     

Replacement of the anterior cruciate ligament by cold preserved bone-cruciate ligament-bone allotransplants. An experimental study in the sheep

One ACL in each of 17 mature sheep was replaced with a deep-frozen bone-an ACL bone allograft. Allografts were obtained from skeletally mature sheep using a standard aseptic technique and stored deep frozen for at least 6 days (mean 21 days). Macroscopical, biomechanical, and histological changes were evaluated 12, 24, and 52 weeks following implantation. At autopsy all allograft ligaments were present and demonstrated no evidence of infection or immune reaction. We found slight arthrotic changes in 3 knees after 12 weeks, in 4 knees after 24 weeks, and in 3 knees after 52 weeks. Twelve weeks after the operation the maximum load of the allografts was 17.5% of the contralateral controls and increased to 20.9% after 24 weeks and to 32% of controls after 52 weeks. Ligament stiffness in the linear region also increased from 18.9% of control (12 weeks) to 32.5% after 52 weeks, whereas maximum load decreased from 112.2% of controls (12 weeks) to 98% of controls (52 weeks). Histologically, the allografts progressively matured with time, becoming nearly identical to normal ligaments at 52 weeks.