Meat color is determined not only by chromatic heme pigments but also by the physical structure and achromatic light scattering properties of the muscle

Meat color is important for consumer acceptability, with excessively dark meat often associated with consumer rejection. It is determined chromatically by pigment content (measured by hue and chroma) and achromatically by scattering of light by the microstructure (measured by lightness), the latter of which has received minimal research focus. This review discusses the individual components of the meat microstructure that cause differences in achromatic contributions to color. Differences in achromatic light scattering between light and dark extremes of meat color are most likely explained by structural attributes within the muscle cell. These differences are proposed to arise from variations in (a) transverse shrinkage of the structural lattice of the myofilaments, myofibrils, and muscles fibers, (b) longitudinal shrinkage of the sarcomere, and (c) different protein composition of the surrounding medium (sarcoplasm and extracellular space). These are discussed at a mechanistic level, in relation to six parameters of the muscle cell: (a) protein surface charge altering the myofilament spacing, (b) protein solubility, (c) sarcoplasmic protein binding to myofilaments and myofibrils, (d) integrity of the cytoskeleton and cell adhesion proteins, (e) sarcomere integrity and myofibrillar proteins, and (f) myosin denaturation and rigor bond modification. New data are presented to support the proposed role of structural elements in muscle causing achromatic light scattering and their contribution to the surface color of meat. In addition, the relationships between lightness and water holding capacity and pH are explored and the economic impact of dark meat for the meat industry is discussed.     

Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells

The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In this study, we determined the effect of pharmacological inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4; receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE; esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by added SAA. Inhibitor activity was also compared to high-density lipoprotein (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA significantly increased gene expression of TF, NFκB and TNF and protein levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement of endothelial cell SAA receptors in pro-atherogenic gene expression. In contrast, HDL consistently showed the greatest inhibitory action, and often abrogated SAA-mediated responses. Increasing HDL levels relative to circulating free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate atherogenesis.     

Disinfection by-product formation after biologically assisted GAC treatment of water supplies with different bromide and DOC content

Chlorination of drinking water in the presence of bromide and dissolved organic carbon (DOC) leads to the formation of brominated and chlorinated disinfection by-products (DBP). The concentration of bromide ions in the raw water is a significant factor in the speciation of DBP formed, and causes shifts in trihalomethane (THM) formation from chlorinated to brominated species. Drinking water treatment techniques that remove organic contaminants without affecting bromide ion concentrations cause increases in the brominated THM. For the present study, three water supplies containing different DOC and ambient bromide concentrations were filtered through biologically assisted granular activated carbon (BGAC). Similar to adsorption and coagulation treatment, this treatment does not remove bromide from drinking water; also, THMFP (trihalomethane formation potential) analysis indicated that the chlorinated effluent contained higher concentrations of brominated THM in comparison to the influent. Although BGAC may increase the brominated THM, which may be more toxic than the chlorinated THM, the overall reduction of THMFP by DOC removal far exceeds this negative change, thereby producing a much less toxic finished drinking water. This work is part of a study to make high DOC surface waters on the Canadian prairie safe and palatable for small volume users (individuals or small communities).     

Discovery of 5′′‐Chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064): A Selective Orexin 2 Receptor Antagonist (2‐SORA) for the Treatment of Insomnia

The field of small‐molecule orexin antagonist research has evolved rapidly in the last 15 years from the discovery of the orexin peptides to clinical proof‐of‐concept for the treatment of insomnia. Clinical programs have focused on the development of antagonists that reversibly block the action of endogenous peptides at both the orexin 1 and orexin 2 receptors (OX₁R and OX₂R), termed dual orexin receptor antagonists (DORAs), affording late‐stage development candidates including Merck’s suvorexant (new drug application filed 2012). Full characterization of the pharmacology associated with antagonism of either OX₁R or OX₂R alone has been hampered by the dearth of suitable subtype‐selective, orally bioavailable ligands. Herein, we report the development of a selective orexin 2 antagonist (2‐SORA) series to afford a potent, orally bioavailable 2‐SORA ligand. Several challenging medicinal chemistry issues were identified and overcome during the development of these 2,5‐disubstituted nicotinamides, including reversible CYP inhibition, physiochemical properties, P‐glycoprotein efflux and bioactivation. This article highlights structural modifications the team utilized to drive compound design, as well as in vivo characterization of our 2‐SORA clinical candidate, 5′′‐chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064), in mouse, rat, dog, and rhesus sleep models.     

Two placebo-controlled crossover studies in healthy subjects to evaluate gastric acid neutralization by an alginate–antacid formulation (Gaviscon Double Action)

Objective: To investigate the intragastric acid neutralization activity of a combined alginate-antacid formulation.

Significance: Published studies have investigated the reflux-suppressing alginate component of Gaviscon Double Action (Gaviscon DA; RB, UK) but intragastric acid neutralization activity of the antacid component has not been evaluated in vivo.

Methods: Intragastric pH monitoring, using a custom-made 10-electrode catheter, was evaluated in a two-part exploratory study in healthy subjects; Part I (n?=?6) tested suitability of the catheter using antacid tablets (Rennie; Bayer, Germany); Part II (n?=?12) evaluated gastric acid neutralization activity of Gaviscon DA liquid (20?ml) versus placebo in fasted subjects using a randomized, open-label, crossover design. The primary endpoint was the percentage of time that intragastric pH ≥4 was measured during 30?min post-treatment. A confirmatory study of identical design was subsequently conducted (n?=?20).

Results: Monitoring pH using the multielectrode catheter was a viable approach, directly detecting changes in intragastric pH following a single dose of antacid tablets. In the exploratory study, the percentage of time that pH ≥4 during 30?minutes post-treatment was 46.8% with Gaviscon DA liquid versus 4.7% with placebo (p?=?0.0004). These findings were supported by the confirmatory study, where pH ≥4 was recorded 50.8% of the time with Gaviscon DA versus 3.5% with placebo (p?=?0.0051). In this study, Gaviscon DA was safe and well tolerated.

Conclusions: These studies demonstrate the effective acid neutralizing capacity of Gaviscon DA versus placebo in healthy, fasted subjects. This adds to the evidence base for the combination of alginates and antacids.     

Significance of Inulin Fructans in the Human Diet

This paper reviews the physicochemical properties and nutritional significance of inulin fructans (oligofructose and inulin). These compounds are naturally present in a large number of food crops and serve in our diet as dietary fiber. Inulin fructans can be isolated and purified from the chicory root and used as ingredients in a large range of foods to improve structure and/or taste and to increase the intake of dietary fiber. Inulin fructans have a low caloric value, are safe, and generally well tolerated up to a level of 20 g/d. They exert a range of effects, which can be differentiated into direct effects on the gut and the intestinal flora and indirect systemic effects. Direct effects on the gut include prebiotic (bifidogenic) effects, improvement of bowel habits and bowel function in constipated subjects, increased colonic absorption of minerals (Ca and Mg), and secretion of satiety hormones. Indirect effects are on blood lipids, bone mineral content, the immune system, and energy homeostasis. These issues are discussed and it is argued that promising avenues for research are particularly in the areas of energy homeostasis and systemic low‐grade inflammation in relation to changes in the composition of the intestinal microbiota.     

Evolution of supramolecular healable composites: a minireview

Efforts to further extend the range of applications of polymer based materials have resulted in the recent production of healable polymers that can regain their strength after damage. Within this field of healable materials, supramolecular polymers have been subject to extensive investigation. By virtue of their reversible non‐covalent interactions, cracks and fractures in such polymers can be readily and repeatedly healed in order to regain key physical properties. However, many supramolecular polymers are relatively weak and elastomeric in nature, which renders them unsuitable for high strength structural applications. To overcome these deficiencies, preliminary studies have shown that it is possible to reinforce supramolecular polymers with microscale and nanoscale fillers to afford composites that are not only stronger and stiffer compared with the polymers alone but also retain their healing abilities. In this minireview we discuss the evolution of these supramolecular composites and their advantages over more conventional, covalent polymeric materials. © 2014 Society of Chemical Industry     

Digital business reporting standards: mapping the battle in France

Government agencies use information technology extensively to collect business data for regulatory purposes. Data communication standards form part of the infrastructure with which businesses must conform to survive. We examine the development of, and emerging competition between, two open business reporting data standards adopted by government bodies in France; Electronic Data Interchange for Administration, Commerce and Transport (EDIFACT) (incumbent) and eXtensible Business Reporting Language (XBRL) (challenger). The research explores whether an incumbent may be displaced in a setting in which the contest is unresolved. Latour's translation map is applied to trace the enrollments and detours in the battle. We find that regulators play an important role as allies in the development of the standards. The antecedent networks in which the standards are located embed strong beliefs that become barriers to collaboration and fuel the battle. One of the key differentiating attitudes is whether speed is more important than legitimacy. The failure of collaboration encourages competition. The newness of XBRL's technology just as regulators need to respond to an economic crisis and its adoption by French regulators not using EDIFACT create an opportunity for the challenger to make significant network gains over the longer term. ANT also highlights the importance of the preservation of key components of EDIFACT in ebXML.