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A hydroponic experiment was conducted to investigate the effects of indole-3-acetic acid (IAA) on arsenic (As) uptake and antioxidative enzymes in fronds ofPteris creticavar.nervosa(As hyperaccumulator) andPteris ensiformis(non-hyperaccumulator). Plants were exposed to 2 mg L−1As(III), As(V) or dimethylarsinic acid (DMA) and IAA concentrations for 14 d. The biomass and total As in the plants significantly increased at 30 mg L−1IAA. Superoxide dismutase (SOD) activities significantly increased with IAA addition. Catalase (CAT) activities showed a significant increase inP. ensiformisexposed to three As species at 30 or 50 mg L−1IAA but varied inP. creticavar.nervosa. Peroxidase (POD) activities were unchanged inP. ensiformisexcept for a significant decrease at 50 mg L−1IAA under As(III) treatment. However, a significant increase was observed inP. creticavar.nervosaat 10 mg L−1IAA under As(III) or DMA treatment and at 50 mg L−1IAA under As(V) treatment. Under DMA stress, malondialdehyde contents in fronds ofP. creticavar.nervosashowed a significant decrease at 10 mg L−1IAA but remained unchanged inP. ensiformis. Therefore, IAA enhanced As uptake and frond POD activity inP. creticavar.nervosaunder As stress. [ABSTRACT FROM PUBLISHER]

PHT1 (SLC15A4) is responsible for translocating l -histidine ( l -His), di/tripeptides and peptide-like drugs across biological membranes. Previous studies have indicated that PHT1 is located in brain parenchyma, however, its role and significance in brain along with effect on the biodistribution of substrates is unknown. In this study, adult gender-matched Pht1 -competent (wildtype) and Pht1 -deficient (null) mice were used to investigate the effect of PHT1 on l -His brain disposition via in vitro slice and in vivo pharmacokinetic approaches. We also evaluated the serum clinical chemistry and expression levels of select transporters and enzymes in the two genotypes. No significant differences were observed between genotypes in serum chemistry, body weight, viability and fertility. PCR analyses indicated that Pept2 had a compensatory up-regulation in Pht1 null mice (about 2-fold) as compared to wildtype animals, which was consistent in different brain regions and confirmed by immunoblots. The uptake of l -His was reduced in brain slices by 50% during PHT1 ablation. The l -amino acid transporters accounted for 30% of the uptake, and passive (other) pathways for 20% of the uptake. During the in vivo pharmacokinetic studies, plasma concentration-time profiles of l -His were comparable between the two genotypes after intravenous administration. Still, biodistribution studies revealed that, when sampled 5 min after dosing, l -His values were 28–48% lower in Pht1 null mice, as compared to wildtype animals, in brain parenchyma but not cerebrospinal fluid. These findings suggest that PHT1 may play an important role in histidine transport in brain, and resultant effects on histidine/histamine homeostasis and neuropeptide regulation. [ABSTRACT FROM AUTHOR]

The effects of ultrasonic vibration temperature on the microstructure of semisolid Sn-52Bi alloy and mechanical properties were investigated. The results show that the microstructure and mechanical properties are improved obviously after the ultrasonic treatment. Nearly round and uniformly distributed primary Sn phase particles were obtained under the cavitation and acoustic streaming caused by ultrasonic treatment. The best effects of ultrasonic treatment on microstructure and mechanical properties were obtained with the ultrasonic vibration for 120 s at 140 °C. The elongation of semisolid Sn-52Bi alloy treated by ultrasonic vibration for 120 s at 140 °C was 42% and increased by 156.09% compared to conventional liquid casting Sn-52Bi alloy without ultrasonic vibration. It is a feasible and effective method to adopt the semisolid metal forming technology assisted with ultrasonic vibration to improve the ductility of Sn-Bi alloys. [ABSTRACT FROM AUTHOR]

The accurate and sensitive detection of chloramphenicol (CAP) is particularly imperative to public health and safety. Here, we present a novel sensor for residual CAP detection based on competitive surface-enhanced Raman scattering (SERS) immunoassay and magnetic separation. In this nanosensor, functionalized Au nanoparticles (AuNPs) were labeled with the Raman reporter molecule (e.g. 4,4′-dipyridyl). With the addition of free CAP, a competitive immune reaction was initiated between free CAP and above AuNPs for conjugating with CAP antibody-modified magnetic nanoparticles (MNPs). Instead of the solid substrate, the antibody conjugated-magnetic beads were used as supporting materials and separation tools in the present sensor. With the aid of a magnet, the mixture was removed from the supernatant for concentration effects. This caused obvious change of SERS signal intensity obtained from supernatant. The SERS signals were collected from the supernatant directly, which made the SERS measurements more stable, repeatable and reliable. The proposed SERS-based magnetic immunosensor allows us to detect CAP in a fast, selective and sensitive (1.0 pg/mL) manner over a wide concentration range ( 1–1×10 4 pg/mL). In addition, these results demonstrate that this immunosensor holds great potential for the detection of antibiotics in real aquatic environment, which is crucial to our life. [ABSTRACT FROM AUTHOR]

PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. Species differences, however, have been observed in PepT1-mediated intestinal absorption and pharmacokinetics, thereby, making it more difficult to predict systemic drug exposure. In the present study, we evaluated the in situ intestinal permeability of the PepT1 substrate cefadroxil in wildtype and humanized PepT1 ( huPepT1 ) mice, and the in vivo absorption and disposition of drug after escalating oral doses. The in situ perfusions indicated that cefadroxil had a twofold higher affinity (i.e., twofold lower K m ) for jejunal PepT1 in huPepT1 mice, lower but substantial permeability in all regions of the small intestine, and low but measureable permeability in the colon as compared to wildtype animals. The in vivo experiments indicated almost superimposable pharmacokinetic profiles between the two genotypes after intravenous bolus dosing of cefadroxil. In contrast, after oral dose escalation, the systemic exposure of cefadroxil was reduced in huPepT1 mice as compared to wildtype animals. Moreover, the AUC and C max versus dose relationships were nonlinear for huPepT1 but not wildtype mice, and similar to that observed from human subjects. In conclusion, our findings indicate that huPepT1 mice may provide a valuable tool in the drug discovery process by better predicting the oral pharmacokinetic profiles of PepT1 substrates in humans. [ABSTRACT FROM AUTHOR]

1. Cefadroxil is a broad-spectrum β-lactam antibiotic that is widely used in the treatment of various infectious diseases. Currently, poor understanding of the drug's pharmacokinetic profiles and disposition mechanism(s) prevents determining optimal dosage regimens and achieving ideal antibacterial responses in patients. In the present retrospective study, we developed a population pharmacokinetic model of cefadroxil in wild-type and Pept2 knockout mice using the nonlinear mixed effect modeling (NONMEM) approach. 2. Cefadroxil pharmacokinetics were best described by a two-compartment model, with both saturable and nonsaturable elimination processes to/from the central compartment. Through this modeling approach, pharmacokinetic parameters in wild-type and Pept2 knockout mice were well estimated, respectively, as follows: volume of central compartment V1 (3.43 versus 4.23 mL), volume of peripheral compartment V2 (5.98 versus 8.61 mL), intercompartment clearance Q (0.599 versus 0.586 mL/min) and linear elimination rate constant K10 (0.111 versus 0.070 min−1). Moreover, the secretion kinetics (i.e. Vm1 = 17.6 nmoL/min and Km1 = 37.1 µM) and reabsorption kinetics (i.e. Vm2 = 15.0 nmoL/min and Km2 = 27.1 µM) of cefadroxil were quantified in kidney, for the first time, under in vivo conditions. 3. Our model provides a unique tool to quantitatively predict the dose-dependent nonlinear disposition of cefadroxil, as well as the potential for transporter-mediated drug interactions. [ABSTRACT FROM AUTHOR]

A rhodamine/coumarin-based ratiometric fluorescent Fe3+ sensor has been designed and synthesized. The sensor exhibits a good response to Fe3+ ions with high sensitivity, selectivity and a large shift in the emission spectra ( 100 nm), which shows Fe3+-induced FRET OFF-ON and PET ON-OFF behavior. [ABSTRACT FROM AUTHOR]

Background and Purpose: 5-Aminolevulinic acid (5-ALA) has been widely used in photodynamic therapy and immunofluorescence of tumours. In the present study, the intestinal permeability and oral pharmacokinetics of 5-ALA were evaluated to probe the contribution of the proton-coupled oligopeptide transporter 1 (PEPT1) to the oral absorption and systemic exposure of this substrate.Experimental Approach: In situ single-pass intestinal perfusions and in vivo oral pharmacokinetic studies were performed in wildtype and Pept1 knockout mice. Perfusion studies were performed as a function of concentration dependence, specificity and permeability of 5-ALA in different intestinal segments. Pharmacokinetic studies were performed after 0.2 and 2.0 μmoL·g(-1) doses of 5-ALA.Key Results: The permeability of 5-ALA was substantial in duodenal, jejunal and ileal regions of wildtype mice, but the residual permeability of 5-ALA in the small intestine from Pept1 knockout mice was only about 10% of that in wildtype animals. The permeability of 5-ALA in jejunum was specific for PEPT1 with no apparent contribution of other transporters, including the proton-coupled amino acid transporter 1 (PAT1). After oral dosing, the systemic exposure of 5-ALA was reduced by about twofold during PEPT1 ablation, and the pharmacokinetics were dose-proportional after the 0.2 and 2.0 µmol·g(-1) doses. PEPT1 had a minor effect on the disposition and peripheral tissue distribution of 5-ALA.Conclusion and Implications: Our findings suggested a major role of PEPT1 in the intestinal permeability and oral absorption of 5-ALA. In contrast, another proton-coupled transporter, PAT1, appeared to play a limited role, at best. [ABSTRACT FROM AUTHOR]