A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging.

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF2 scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field. Content includes material subject to Dstl (c) Crown copyright (2014). Licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@ nationalarchives.gsi.gov.uk.

Transesterification of p-hydroxybenzoate esters (parabens) by human intestinal (Caco-2) cells.

p-Hydroxybenzoate ester (paraben) preservatives are used in numerous orally administered products. The recognized route of metabolism for parabens is hydrolysis to p-hydroxybenzoic acid followed by conjugation and excretion. However, in the presence of alcohols, a presystemic transesterification pathway not previously reported for the human intestine can occur. Using human intestinal (Caco-2) cells, it was observed that hydrolysis of parabens to p-hydroxybenzoic acid is reduced markedly by ethanol concentrations that can occur in the human intestine, 0.25-0.5% (v/v). Ethanol concentrations of 1.0-2.5% (v/v) were optimal for transesterification to ethylparaben in Caco-2 cell homogenates. The kinetics of the transesterification reaction with regard to ethanol concentration (0-20%), time, pH (3-9), protein concentration (1-5 mg ml-1) and substrate concentration (6.25-200 microM) as well as the effects of different alcohols were studied. The Km and Vmax values for transesterification with ethanol for methyl, propyl, butyl, heptyl and octyl parabens were 449.7, 165.7, 86.1, 24.2 and 45.9 microM and 114.4, 37.5, 19.5, 7.5 and 7.6 micromol h-1 mg-1 Caco-2 cell protein, respectively. The Vmax values for transesterification of methylparaben with ethanol, propan-1-ol, butan-1-ol were 114.4, 5.1 and 4.9 micromol h-1 mg-1, respectively. Collectively, the kinetic data demonstrate that the enzyme responsible for the transesterification reaction has a preference for short-chain esters and represents the first report of transesterification in human intestinal cells. An implication of this mechanism is that alcohol-containing in vitro biosystems or protocols for the study of parabens disposition could generate transesterified artefacts. The clinical or toxicological implication is that, following co-ingestion of ester compounds with ethanol, transesterification could provide the basis for a previously unrecognized drug-alcohol interaction.

Almokalant glucuronidation in human liver and kidney microsomes: evidence for the involvement of UGT1A9 and 2B7.

1. Almokalant, a class III antiarrythmic drug, is metabolized to form isomeric glucuronides identified in human urine. Synthesis of the total glucuronide was studied in human liver and kidney microsomes. Recombinant UDP-glucuronosyltransferases (UGTs) were screened for activity and kinetic analysis was performed to identify the isoform(s) responsible for the formation of almokalant glucuronide in man. 2. From a panel of recombinant isoforms used, both UGT1A9 and 2B7 catalysed the glucuronidation of almokalant. The Km values in both instances were similar with 1.06 mM for the 1A9 and 0.97 mM for the 2B7. Vmax for 1A9 was fourfold higher than that measured for UGT2B7, 92 compared with 21 pmol min(-1) mg(-1), respectively, but UGT1A9 was expressed at approximately twofold higher level than the UGT2B7 in the recombinant cell lines. Therefore, the contribution of UGT2B7 to almokalant glucuronidation could be as significant as that of UGT1A9 in man. 3. Liver and kidney microsomes displayed similar Km values to the cloned expressed UGTs, with the liver and kidney microsomes at 1.68 and 1.06 mM almost identical to the 1A9. 4. The results suggest a significant role for UGT1A9 and 2B7 in the catalysis of almokalant glucuronidation.