Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis

Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75432/1/j.1365-2222.2006.02498.x.pd

Cell signalling by reactive lipid species: new concepts and molecular mechanisms

The process of lipid peroxidation is widespread in biology and is mediated through both enzymatic and non-enzymatic pathways. A significant proportion of the oxidized lipid products are electrophilic in nature, the RLS (reactive lipid species), and react with cellular nucleophiles such as the amino acids cysteine, lysine and histidine. Cell signalling by electrophiles appears to be limited to the modification of cysteine residues in proteins, whereas non-specific toxic effects involve modification of other nucleophiles. RLS have been found to participate in several physiological pathways including resolution of inflammation, cell death and induction of cellular antioxidants through the modification of specific signalling proteins. The covalent modification of proteins endows some unique features to this signalling mechanism which we have termed the ‘covalent advantage’. For example, covalent modification of signalling proteins allows for the accumulation of a signal over time. The activation of cell signalling pathways by electrophiles is hierarchical and depends on a complex interaction of factors such as the intrinsic chemical reactivity of the electrophile, the intracellular domain to which it is exposed and steric factors. This introduces the concept of electrophilic signalling domains in which the production of the lipid electrophile is in close proximity to the thiol-containing signalling protein. In addition, we propose that the role of glutathione and associated enzymes is to insulate the signalling domain from uncontrolled electrophilic stress. The persistence of the signal is in turn regulated by the proteasomal pathway which may itself be subject to redox regulation by RLS. Cell death mediated by RLS is associated with bioenergetic dysfunction, and the damaged proteins are probably removed by the lysosome-autophagy pathway

SKIN SURFACE + BONE/FRAME, Design through Metaphor and Scale

The design studio is the heart of Interior Architecture education. It is the spring board for future designers and is the main forum for creative exploration, critical thinking, discussion, development and reflection. Our future designers need to be disciplined, analytical yet flexible thinkers, who are able to address and resolve new and complex problems. This paper reviews the progression and development of an experimental design studio over three years. The studio was established to gauge students' design understanding through drawing and modelling, thereby providing a common tool for discussion. This process raised a number of concerns relating to their understanding of scale, detail and human occupation. Therefore the studio approach was revised to incorporate full-scale sectional models constructed from light-weight materials. The students were inspired to build on their knowledge and creative thinking abilities through a series of explorative exercises and modelling. They thus achieved a greater understanding of scale, detail and design tectonics. The learning experience of students undertaking this studio was enabled and guided by teachers experienced in both university teaching and creative practice, as strategic teaching is central to the creative development process. Through an exploration of the evolving studio process, this paper will show the effectiveness of a pedagogical approach that enables students to bring ideas to life by combining drawing and modelling with full-scale three-dimensional design models. This approach and practice enables students to develop their strengths as designers, as they inhabit their designs and appreciate the human scale

MathDox : a system for interactive mathematics

We discuss the MathDox system, a system for presenting highly interactive mathematical documents. The system consists of both an XML format for interactive mathematical documents as well as a server for these documents called the MathDox Player

WExEd : WebALT exercise editor for multilingual mathematical exercises

Recently, the computer program WExEd was developed within the WebALT project. It enables one to create and edit interactive mathematics exercises that can be automatically translated to and subsequently played in different languages (currently English, Spanish, Finnish, Swedish and Italian). It makes use of OpenMath, a standard for encoding the semantics of mathematical objects in XML, and software developed within WebALT. WExEd does not only encode the mathematics of the exercise in OpenMath but also the text. This is possible because, in general, mathematics exercises are built from a well defined and relatively small set of words. In this paper we give a presentation of WExEd

MathDox : a system for interactive mathematics

We discuss the MathDox system, a system for presenting highly interactive mathematical documents. The system consists of both an XML format for interactive mathematical documents as well as a server for these documents called the MathDox Player