Multicentre evaluation of the Monarch (IL) clinical chemistry analyser

A multicentre evaluation of the Monarch centrifugal analyser is reported. Precision, linearity and accuracy were assessed by comparison with routine methods. Calibration stability, photometric and dispensing accuracy, and carry-over related to samples and reagents were also evaluated. The overall performance of the instrument was good, showing an excellent photometric and dispensing accuracy, absence of sample-dependent carry-over, and almost negligible reagent carry-over. Good precision, linearity and correlation with routine methods were found for the parameters tested. The instrument is reliable and is now used as the routine clinical chemistry analyser in two of the three laboratories taking part in the evaluation.     

New Pacidamycin Antibiotics Through Precursor‐Directed Biosynthesis

Pacidamycins, mureidomycins and napsamycins are structurally related uridyl peptide antibiotics that inhibit translocase I, an as yet clinically unexploited target. This potentially important bioactivity coupled to the biosynthetically intriguing structure of pacidamycin make this natural product a fascinating subject for study. A precursor‐directed biosynthesis approach was employed in order to access new pacidamycin derivatives. Strikingly, the biosynthetic machinery exhibited highly relaxed substrate specificity with the majority of the tryptophan analogues that were administered; this resulted in the production of new pacidamycin derivatives. Remarkably, 2‐methyl‐, 7‐methyl‐, 7‐chloro‐ and 7‐bromotryptophans produced their corresponding pacidamycin analogues in larger amounts than the natural pacidamycin. Low levels or no incorporation was observed for tryptophans substituted at positions 4, 5 and 6. The ability to generate bromo‐ and chloropacidamycins opens up the possibility of further functionalising these compounds through chemical cross‐coupling in order to access a much larger family of derivatives.     

Synthesis and Evaluation of 1‐(1‐(Benzo[b]thiophen‐2‐yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase

Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP ( 1 , 1‐(1‐benzo[b]thiophen‐2‐yl‐cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K_i=1 μM ) and biologically active against bloodstream T. brucei (EC₅₀=10 μM ), but with poor selectivity against mammalian MRC5 cells (EC₅₀=29 μM ). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed.     

Laboratory studies into how glass-reinforced plastic (GRP) vat surfaces can be repaired without causing migration of styrene into foodstuffs

Glass–fiber-reinforced plastic (GRP) vats are used widely for the storage of foodstuffs and potable water. As the inner surfaces deteriorate during decades of use, they need to be repaired. The unsaturated polyester resins that are used for recoating are crosslinked with styrene which can cause taint and odor problems. This article describes some coating parameters that affect the content of residual styrene and its subsequent migration. The influences of cure temperature and duration, along with the effect of washing with warm detergent solution, were investigated. Cured specimens were tested for their residual styrene content and for styrene migration into the food simulants, distilled water, 3% acetic acid, and 15% ethanol. The dominant factor in reducing the amount of residual styrene is the temperature. The resin self-heats as it cures, typically up to 50°C. Thus, any further lowering of the styrene content requires a higher cure temperature than this. A 3-h cure at 80°C reduced both the residual content and the migration levels by about 100-fold. At lower cure temperatures, the heating effect of washing at 60°C is more important than the washing effect of the detergent. When less catalyst was used the residual styrene levels rose dramatically, from 70 to 360 to 1300 mg/kg for the normal dose, half and quarter the normal dose, respectively. There was a linear relationship between residual content in the GRP and the migration levels. This correlation could be used for monitoring the quality of vats repaired in situ, using styrene-based coating resins.     

Host Recognition by the Specialist Hoverfly <Emphasis Type="Italic">Microdon mutabilis</Emphasis>, a Social Parasite of the Ant <Emphasis Type="Italic">Formica lemani</Emphasis>

The larva of the hoverfly Microdon mutabilis is a specialist social parasite of the ant Formica lemani that is adapted to local groups of F. lemani colonies but mal-adapted to colonies of the same species situated only a few hundred meters away. At a study site in Ireland, F. lemani shares its habitat with four other ant species. All nest under stones, making the oviposition choice by M. mutabilis females crucial to offspring survival. In this study, we tested the hypothesis that, as an extreme specialist, M. mutabilis should respond to cues derived from its host rather than from its microenvironment, a phenomenon that has hitherto only been addressed in the context of herbivorous insects and their parasitoids. In behavioral assays, M. mutabilis females reacted to volatiles from F. lemani colonies by extending their ovipositors, presumably probing for an oviposition substrate. This behavior was not observed toward negative controls or volatiles from colonies of Myrmica scabrinodis, the host ant of the closely related Microdon myrmicae. Coupled gas chromatography-electroantennography (GC-EAG) that used antennal preparations of M. mutabilis located a single physiologically active compound within an extract of heads of F. lemani workers. Coupled GC-mass spectrometry (GC-MS) tentatively identified the compound as a methylated methylsalicylate. GC co-injection of the extract with authentic samples showed that of the four possible isomers (methyl 3-, 4-, 5-, and 6-methylsalicylate), only methyl 6-methylsalicylate co-eluted with the EAG-active peak. Furthermore, the response to methyl 6-methylsalicylate was four times higher than to those of the other isomers. Coupled GC-EAG and GC-MS also revealed physiological responses to two constituents, 3-octanone and 3-octanol, of the M. scabrinodis alarm pheromone. However, the behavioral trials did not reveal any behavior that could be attributed to these compounds. Results are discussed in the context of four phases of host location behavior, and of the characteristics, which volatile cues should provide to be useful for an extreme specialist such as M. mutabilis.     

On the Synergy Effect in MoO3–Fe2(MoO4)3 Catalysts for Methanol Oxidation to Formaldehyde

Methanol oxidation to formaldehyde was studied over a series of Fe–Mo–O catalysts with various Mo/Fe atomic ratio and the end compositions Fe₂O₃ and MoO₃. The activity data show that the specific activity passes through a maximum with increase of the Mo content and is the highest for Fe₂(MoO₄)₃. The selectivity to formaldehyde, on the other hand, increases with the Mo content in the catalyst. A synergy effect is observed in that a catalyst with the Mo/Fe ratio 2.2 is almost as active as Fe₂(MoO₄)₃ and as selective as MoO₃. Imaging of a MoO₃/Fe₂(MoO₄)₃ catalyst by SEM and TEM shows that the two phases form separate crystals, and HRTEM reveals the presence of an amorphous overlayer on the Fe₂(MoO₄)₃ crystals. EDS line-scan analysis in STEM mode demonstrates that the Mo/Fe ratio in the amorphous layer is ~2.1 in the fresh catalyst and ~1.7 in the aged catalyst. The enrichment of Mo at the catalyst surface is confirmed by XPS data. Raman spectra give evidence for the Mo in the amorphous material being in octahedral coordination, which is in contrast to the crystalline Fe₂(MoO₄)₃ bulk structure where Mo has tetrahedral coordination. X-ray diffraction (XRD) analysis gives no support for the formation of a defective molybdate bulk structure. The results presented give strong support for the Mo rich amorphous structure being observed on the Fe₂(MoO₄)₃ crystal surfaces being the active phase for methanol oxidation to formaldehyde.     

Atomic force microscopy and contact angle studies of polymerizable gemini surfactant admicelles on mica

Atomic force microscopy (AFM) was used to directly observe and characterize a polymer‐modified mica surface prepared using a polymerizable gemini surfactant. Normal tapping mode and contact mode AFM were used to image the treated mica surface morphologies in air and liquid environments, respectively. The root mean square (RMS) roughness of mica surfaces before and after surface modification and polymerization was analyzed from these scans. To determine the effect of styrene adsolubilization on the surfactant‐modified mica, AFM measurements of the modified mica were made at various styrene concentrations. Contact angle measurements were also made to further characterize the nature of the surfactant‐modified mica surface. The surface morphology and surface hydrophilicity were observed to be different for the modified mica after polymerization. In addition, the polymerized surface maintained its morphology after washing/desorption studies demonstrating the stability of the polymerized surfactant film. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Styrene and Phenylethanol Adsolubilization of a Polymerizable Gemini Surfactant

A polymerizable gemini surfactant was used to adsolubilize styrene and phenylethanol, representing less and more polar organic solutes, respectively, in order to evaluate the impact of admicellar polymerization on the adsolubilization process. Adsolubilization was also evaluated using a polymerizable monomeric surfactant and conventional surfactant for comparison purposes. The main results were that: (1) polymerized and unpolymerized admicelles showed similar adsolubilization potential—validating the use of polymerized admicelles without sacrificing adsolubilization, and (2) gemini surfactants showed adsolubilization capacities equal to or higher than conventional surfactants.     

Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE

Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX’s effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.