Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid

Oxidized LDL is present within atherosclerotic lesions, demonstrating a failure of antioxidant protection. A normal human serum ultrafiltrate of M-r below 500 was prepared as a model for the low M-r components of interstitial fluid, and its effects on LDL oxidation were investigated. The ultrafiltrate (0.3%, v/v) was a potent antioxidant for native LDL, but was a strong prooxidant for mildly oxidized LDL when copper, but not a water-soluble azo initiator, was used to oxidize LDL. Adding a lipid hydroperoxide to native LDL induced the antioxidant to prooxidant switch of the ultrafiltrate. Uric acid was identified, using uricase and add-back experiments, as both the major antioxidant and prooxidant within the ultrafiltrate for LDL. The ultrafiltrate or uric acid rapidly reduced Cu2+ to Cu+. The reduction of Cu2+ to Cu+ may help to explain both the antioxidant and prooxidant effects observed. The decreased concentration of Cu2+ would inhibit tocopherol-mediated peroxidation in native LDL, and the generation of Cu+ would promote the rapid breakdown of lipid hydroperoxides in mildly oxidized LDL into lipid radicals. The net effect of the low M-r serum components would therefore depend on the preexisting levels of lipid hydroperoxides in LDL.jlr These findings may help to explain why LDL oxidation occurs in atherosclerotic lesions in the presence of compounds that are usually considered to be antioxidants.

Quantum mechanics studies of the tautomers of dlhydrodiacetylformoin, an important Maillard intermediate and the synthesis of furaneol

Conformational analyses have been carried out on the acyclic and cyclic forms of dihydrodiacetylformoin, an important Maillard intermediate and precursor for furaneol. For the acyclic forms, the 2,5-dicarbonyl isomers have the lowest energy, while for the cyclic forms, the 3-carbonyl are favoured over the 4-carbonyl isomers. The likely path for cyclisation is investigated and it is shown that the favoured path is dependent upon the relative chiralities of the carbon atoms and in particular that the reaction proceeds more readily if C2 and C3 have different chiralities. After cyclisation, the reaction path to produce furaneol proceeds via the loss of a water molecule. This reaction has been studied with a model including two water molecules and a hydroxide anion and shows relatively low-energy barriers. (C) 2008 Published by Elsevier B.V.

Communities of practice in construction case study organisations: questions and insights

Purpose – At the heart of knowledge management (KM) are the people – an organisation's important knowledge asset. Although this is widely acknowledged, businesses seldom understand this axiom in terms of the communities through which individuals develop and share the capacity to create and use knowledge. It is the collective learning that takes place within the social systems, i.e. communities of practice (CoP) that are of particular significance to an organisation from a KM perspective. This paper aims to review, critique, and raise some pertinent questions on the role of CoPs; and with the help of case studies shed light on the “goings-on” in construction practices. Design/methodology/approach – After critically reviewing the literature on CoPs and querying some underlying assertions, this research investigates how these issues are addressed in practice. A case study approach is adopted. Three organisations operating in the construction sector are interviewed for the purpose of this paper. Findings – Case study findings highlight the potential challenges and benefits of CoPs to a construction organisation, the role they play in generating and delivering value to the organisation and their contribution towards the collective organisational intelligence. From the findings, it is clear that the question is not whether communities exist within organisations, but how they deliver value to the organisation. From an organisational perspective, the key challenge is to provide an environment that is conducive to developing and nurturing such communities as opposed to merely creating them. Practical implications – Challenges and benefits demonstrated through the case studies should be taken in context. The findings are not intended to be prescriptive in nature, but are intentionally descriptive to provide contextual data that allow readers to draw their own inferences in the context of their organisations. They should be applied taking into account an organisation's unique characteristics and differentiators, the dynamics of the environment in which it operates and the culture it harbours within. Originality/value – Investigating the role of CoPs in the context of case study construction organisations forms the prime focus of this paper.

Literature, literacy and the discourses of English teaching: a case study

This article examines the discourses of English teaching, and their implications for subject and literacy teaching and learning. Case study evidence is presented to illustrate the ways in which competing discourses are enacted in the classroom. We argue the need to critically examine the educational value of teacher discourses, which have an important impact on instructional practices and the quality of pupils' learning.

Potato glycoalkaloids: formation and strategies for mitigation

With the increasing production and consumption of potato and its products, glycoalkaloid (GA) formation and toxicity are likely to become an important focus for food safety researchers and public health agencies. Not only the presence of GA, particularly in the form of a-solanine and a-chaconine, but also the changes occurring as a result of various post-harvest handling practices and storage, are critical issues influencing the quality of stored potatoes. Studies on various factors (pre-harvest, during harvest anal post-harvest) affecting GA have been carried out from time to time, but it is difficult to compare the results of one study with another due to wide variation in the parameters chosen. This review aims to develop a clear understanding of these issues. Published information on the types of GA, their effects on health, their typical concentrations in potatoes, their formation mechanisms, and how their levels can be controlled by following appropriate post harvest practices and storage regimes are critically analysed. The levels of GA in potato can be controlled effectively by adopting appropriate post-harvest practices. Further studies are necessary, however, to investigate best practices, which either check completely or retard substantially their formation. (C) 2008 Society of Chemical Industry.

Quantum mechanics studies of the tautomers of diacetylformoin, an important maillard product and odorant

Diacetylformoin (3,4-dihydroxy-3-hexene-2,5-dione) has 16 tautomers, many with several possible conformations and all have been geometry optimised using quantum mechanics at the HF/6-31+G* level. Eleven structures have been identified with energies within 10 kcal mol(-1) of the minimum energy structure. Of these eight are acyclic and three cyclic. Calculations of NMR spectra have clarified the identity of the acyclic and cyclic structures found experimentally. The mechanism for cyclisation has been investigated and transition states obtained. The lowest energy reaction path requires the loss and gain of a proton during cyclisation. (c) 2006 Elsevier B.V. All rights reserved.

Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods: Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion: At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken.

Ocean data dissemination: new challenges for data integration

In the decade since OceanObs `99, great advances have been made in the field of ocean data dissemination. The use of Internet technologies has transformed the landscape: users can now find, evaluate and access data rapidly and securely using only a web browser. This paper describes the current state of the art in dissemination methods for ocean data, focussing particularly on ocean observations from in situ and remote sensing platforms. We discuss current efforts being made to improve the consistency of delivered data and to increase the potential for automated integration of diverse datasets. An important recent development is the adoption of open standards from the Geographic Information Systems community; we discuss the current impact of these new technologies and their future potential. We conclude that new approaches will indeed be necessary to exchange data more effectively and forge links between communities, but these approaches must be evaluated critically through practical tests, and existing ocean data exchange technologies must be used to their best advantage. Investment in key technology components, cross-community pilot projects and the enhancement of end-user software tools will be required in order to assess and demonstrate the value of any new technology.

Conserved hydrophobic clusters on the surface of the Caf1A usher C-terminal domain are important for F1 antigen assembly

The outer membrane usher protein Caf1A of the plague pathogen Yersinia pestis is responsible for the assembly of a major surface antigen, the F1 capsule. The F1 capsule is mainly formed by thin linear polymers of Caf1 (capsular antigen fraction 1) protein subunits. The Caf1A usher promotes polymerization of subunits and secretion of growing polymers to the cell surface. The usher monomer (811 aa, 90.5 kDa) consists of a large transmembrane β-barrel that forms a secretion channel and three soluble domains. The periplasmic N-terminal domain binds chaperone-subunit complexes supplying new subunits for the growing fiber. The middle domain, which is structurally similar to Caf1 and other fimbrial subunits, serves as a plug that regulates the permeability of the usher. Here we describe the identification, characterization, and crystal structure of the Caf1A usher C-terminal domain (Caf1A(C)). Caf1A(C) is shown to be a periplasmic domain with a seven-stranded β-barrel fold. Analysis of C-terminal truncation mutants of Caf1A demonstrated that the presence of Caf1A(C) is crucial for the function of the usher in vivo, but that it is not required for the initial binding of chaperone-subunit complexes to the usher. Two clusters of conserved hydrophobic residues on the surface of Caf1A(C) were found to be essential for the efficient assembly of surface polymers. These clusters are conserved between the FGL family and the FGS family of chaperone-usher systems.

Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation

The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non‐tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa‐induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra‐, inter‐ and extra‐cellular mechanisms of action, we demonstrate that non‐Δ9tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

A policy critique of Stansted Airport's expansion to 25 million passengers per annum (MPPA)

In this paper we undertake a preliminary assessment of the regional planning and development implications of BAA Stansted Airport’s planning permission to grow to 25 million passengers per annum (mppa) by 2010. Our concern is not simply to consider the overall growth of the airport on the airport site itself but the nature and type of growth both on- and off-site. In this document we focus on the submitted planning permission documents and test them. The methodology we employed was to draw on published and unpublished numerical estimates of the airport’s growth – particularly including estimates produced by the airport owner, BAA, and their economic and planning consultants DTZ Pieda - and critically, and systematically analyse their figures. We adopted this approach because unless the figures which were employed in the initial calculations were correct then all of the subsequent projections which flow from them - and the polices which could then be based on them – could be flawed. The analysis is divided into two parts – firstly, are the growth forecasts correct?; and secondly, what do these forecasts actually mean in developmental terms? In effect, what we have done is to produce a critique of the existing body of evidence by questioning underpinning assumptions and then draw some preliminary conclusions for the region based on this analysis. A major focus of this report has been analyse the figures involved in the planning application to expand Stansted to 25mppa. Ironically, one of our key findings, that the local impact of Stansted’s proposed expansion in employment terms might well be less than was originally thought, might make it easier to gain the acceptance of the relevant local authorities involved to allow the development to take place. Our main overall findings are that the BAA projections over-estimate the local employment impact of the airport’s proposed growth and under-estimate its potential regional ‘transportation’ employment effect. These two findings are, of course, related to each other in important ways, and we also feel that they have potentially significant medium and long-term economic, competitiveness and planning policy implications for the East of England region