Testing Topical Products Specifically to Reduce Inflammatory Pain from Gout: Transdermal NSAID Delivery and Monosodium Urate Solubility.

Purpose: Gout is caused by crystals of monosodium urate (MSU) in the joints. Topical nonsteroidal anti-inflammatory drug products (NSAIDs) are often the first-choice immediate treatment. This study examined the effect of commercially available and newly developed transdermal NSAID products on the solubility of MSU in a physiologically relevant system, alongside the efficacy of transdermal NSAID delivery. Materials and Methods: Drug permeability of 7 commercially available topical NSAID products, alongside 3 newly developed "Gout Buster" products, was evaluated in vitro using pig's ear skin in Franz diffusion cells. The standard Franz cell experimental protocol was adapted to include assessment of MSU solubility in phosphate buffered saline for each product. Some materials were also tested via direct solubility studies. Results: The amount of drug delivered transdermally varied significantly between different formulations, with the best ibuprofen delivery being ~5 times higher than the lowest, and best diclofenac delivery being ~3.5 times higher than the lowest. Changes in formulations and the drug concentration in the product both affected the amount of drug delivered. Overall ibuprofen permeation was higher than diclofenac. The commercially available products showed little or no effect on the MSU solubility (99-103% vs control). The Gout Buster products showed significant improvement in the MSU solubility after permeation through skin (120-126%). Increased sodium levels reduced the solubility of MSU in direct solubility studies. Conclusion: In these trials, the Gout Buster products showed significantly improved permeation of both ibuprofen and diclofenac over the commercial products at similar drug concentrations, and showed significant improvement for MSU solubility. Increased sodium levels reduced the solubility of MSU and could cause more crystallisation in vivo. Therefore, topical NSAID products with the Gout Buster formulation may have the best likelihood of both reducing inflammation and helping re-dissolve the MSU crystals that cause gout.

Redevelopment 'challenged conventional wisdom'.

In a paper awarded 'Best Member Paper' at the 2016 Institute of Hospital Engineering, Australia (IHEA) National Conference held at the Adelaide Oval last October, Mark Hooper BEng, executive project manager at Echuca Regional Health in Victoria, Australia, describes a A$66 million redevelopment project at the hospital--which is located in the historic port town of Echuca on the Murray river, two and a half hours north of Melbourne. He highlights some of the significant innovation that went into the project, in areas including plant operation and maintenance, emergency planning, resilience, and patient and staff comfort.

Development and validation of the first high performance-lateral flow immunoassay (HP-LFIA) for the rapid screening of domoic acid from shellfish extracts.

A lateral flow immunoassay (LFIA) has been developed and fully validated to detect the primary amnesic shellfish poisoning (ASP) toxin, domoic acid (DA). The performance characteristics of two versions of the test were investigated using spiked and naturally contaminated shellfish (mussels, scallops, oysters, clams, and cockles). The tests provide a qualitative result, to indicate the absence or presence of DA in extracts of shellfish tissues, at concentrations that are relevant to regulatory limits. The new rapid assay (LFIA version 2) was designed to overcome the performance limitations identified in the first version of the assay. The improved test uses an electronic reader to remove the subjective nature of the generated results, and the positive cut-off for screening of DA in shellfish was increased from 10 ppm (version 1) to 17.5 ppm (version 2). A simple extraction and test procedure was employed, which required minimal equipment and materials; results were available 15 min after sample preparation. Stability of the aqueous extracts at room temperature (22 °C) at four time points (up to 245 min after extraction) and across a range of DA concentrations was 100.3±1.3% and 98.8±2.4% for pre- and post-buffered extracts, respectively. The assay can be used both within laboratory settings and in remote locations. The accuracy of the new assay, to indicate negative results at or below 10 ppm DA, and positive results at or above 17.5 ppm, was 99.5% (n=216 tests). Validation data were obtained from a 2-day, randomised, blind study consisting of multiple LFIA lots (n=3), readers (n=3) and operators (n=3), carrying out multiple extractions of mussel tissue (n=3) at each concentration (0, 10, 17.5, and 20 ppm). No matrix effects were observed on the performance of the assay with different species (mussels, scallops, oysters, clams, and cockles). There was no impact on accuracy or interference from other phycotoxins, glutamic acid or glutamine with various strip incubations (8, 10, and 12 min). The accuracy of the assay, using naturally contaminated samples to indicate negative results at or below 12.5 ppm and positive results at or above 17.5 ppm, was 100%. Variability between three LFIA lots across a range of DA concentrations, expressed as coefficient of variation (% CV), was 1.1±0.4% (n=2 days) based on quantitative readings from the electronic reader. During an 8 week stability study, accuracy of the method with test strips stored at various temperatures (6, 22, 37 and 50 °C) was 100%. Validation for both versions included comparisons with results obtained using reference LC-UV methods.

The geography of mercury and PCBs in North Carolina's local seafood.

Mercury and PCBs are used by non-governmental organizations and federal agencies to inform seafood safety recommendations. Pollution dynamics suggest recommendations on the national scale may be too large to be accurate. We tested softshell and hardshell blue crab, white and pink shrimp, oysters, clams, spot, and mullet from fishers in each of the three North Carolina fishery districts. We measured mercury using EPA method 7473 and PCBs using a commercially available ELISA kit. Over 97% of samples were below the Environmental Protection Agency levels of concern for both mercury and PCBs. Mercury and PCBs have different spatial dynamics, but both differ significantly by water body, suggesting that seafood safety recommendations should occur by water body instead of at the national scale. This finding supports previous research suggesting that differences in water chemistry, terrestrial influence, and flushing time in a particular water body control the contaminant load in locally resident species.

Bulky triarylarsines are effective ligands for palladium catalysed Heck olefination.

The four arsines, As{C6H3(o-CH3)(p-Z)}3{Z=H (2a) or OMe (2b)} and As{C6H3(o-CHMe2)(p-Z)}3{Z=H (2c) or OMe (2d)} react with [PdCl2(NCPh)2] or [PtCl2(NCBu(t))2] to give trans-[MCl2L2] or trans-[M2Cl2(mu-Cl)2L2]. The crystal structures of trans-[PdCl2(2a)2] and [PtCl2(2d)2] have been determined, the latter as its dichloromethane solvate. The structures show that in these complexes, the ligands adopt gga type conformations as do all analogous tri-o-tolyl- and tri-o-isopropylphenylphosphines in square-planar and octahedral complexes. The variable-temperature NMR behaviour of the complexes shows that they are fluxional due to restricted As-C bond rotation. The rate of the fluxionality is more rapid than in the analogous phosphine complexes and this is associated with longer As-C and As-M bonds allowing more free movement. The catalytic activity of the palladium complexes of the arsines and their phosphine analogues for the reaction of 4-bromoacetophenone and n-butyl acrylate has been screened. The results show that the arsines are generally superior to the phosphines as ligands for this catalysis. Tri(o-isopropylphenyl)phosphine and tri(o-isopropylphenyl)arsine are superior to tri-o-tolylphosphine as ligands for this Heck reaction and a p-methoxy substituent improves the arsine catalyst but not the phosphine catalyst. The phosphine catalysts are superior to the arsine catalysts for the reaction of 4-chloroacetophenone and n-butyl acrylate. These observations are discussed in the context of ligand stereoelectronic effects, as measured by the Tolman electronic parameter, nuCO of the [NiL(CO)3]{L=AsAr3 or PAr3}.

Scope and mechanism of palladium-catalyzed amination of five-membered heterocyclic halides.

Detailed studies have been conducted to determine the activity of palladium catalysts for the amination of five-membered heterocyclic halides and to determine the factors that control the scope of this reaction. Palladium-catalyzed aminations of the electron-rich furanyl, thiophenyl, and indolyl halides and of the related 2-halogenated thiazoles, benzimidazole, and benzoxazole have been shown to occur with a subset of amines. Various combinations of palladium precursors and P(t)Bu(3) were tested as catalysts for reaction of 3-bromothiophene with N-methylaniline, and the fastest reactions occurred with the Pd(I) dimer, [PdBr(P(t)Bu(3))](2). The fastest aminations of thiazoles, benzimidazoles, and benzoxazoles occurred with the combination of palladium trifluoroacetate and P(t)Bu(3) as catalyst.