Objectives: To investigate side by side the effects on serum lipoproteins and postprandial glucose and insulin concentrations of beverages enriched with 5 or 10 g of b-glucans from oats or barley. Design and setting: An 8-week single blind, controlled study with five parallel groups carried out at two centres under identical conditions. Subjects: A total of 100 free-living hypercholesterolaemic subjects were recruited locally and 89 completed the study.

Integrins are a family of heterodimeric adhesion receptors that mediate cellular interactions with a range of matrix components and cell surface proteins. Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial cell ligand for two leukocyte integrins (␣4␤1 and ␣4␤7). A related CAM, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is recognized by ␣4␤7 but is a poor ligand for ␣4␤1. Previous studies have revealed that all ␣4 integrin-ligand interactions are dependent on a key acidic ligand motif centered on the CAM domain 1 C-D loop region. By generating VCAM-1/MAdCAM-1 chimeras and testing recombinant proteins in cell adhesion assays we have found that ␣4␤1 binds to the MAdCAM-1 adhesion motif when present in VCAM-1, but not when the VCAM-1 motif was present in MAdCAM-1, suggesting that this region does not contain all of the information necessary to determine integrin binding specificity. To characterize integrin-CAM specificity further we measured ␣4␤1 and ␣4␤7 binding to a comprehensive set of mutant VCAM-1 constructs containing amino acid substitutions within the predicted integrin adhesion face. These data revealed the presence of key "regulatory residues" adjacent to integrin contact sites and an important difference in the "footprint" of ␣4␤1 and ␣4␤7 that was associated with an accessory binding site located in VCAM-1 Ig domain 2. The analogous region in MAdCAM-1 is markedly different in size and sequence and when mutated abolishes integrin binding activity.Under normal conditions, leukocytes exhibit a weakly adhesive phenotype, however, at sites of inflammation or at specialized lymphoid tissues, leukocyte adhesion receptor activity is modulated and cells become capable of interacting with ligands expressed on the lumenal surface of the vasculature. Leukocyte integrin receptors and endothelial immunoglobulin superfamily cell adhesion molecules (IgCAMs) make key contributions to the events that facilitate leukocyte emigration into the tissues (1, 2).Integrins are ␣/␤ heterodimeric cell surface adhesion receptors that recognize a wide variety of extracellular ligands (3). For most integrins, the mechanism of ligand recognition appears to be critically dependent upon one of two short acidic peptide motifs: RGD and LDV (4, 5). Several extracellular matrix molecules express the RGD motif in an invariant form and are ligands for a number of integrins (e.g. ␣5␤1, ␣IIb␤3, ␣v␤1, ␣v␤3; Refs. 6 -10). In contrast, the LDV motif exhibits sequence variation. For example, the leukocyte integrins ␣4␤1 and ␣4␤7 recognize an LDVP motif in fibronectin (11-15), an IDSP sequence in the N-terminal domain of IgCAM vascular cell adhesion molecule-1 (VCAM-1) 1 (16 -22), and an LDTS sequence in a second IgCAM, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) (23-26).Integrin-ligand interactions can be perturbed by short peptides based on RGD or LDV. Interestingly LDV-containing peptides (and small peptide mimetics) competitively inhibit ␣4␤1 interactions with both fibronectin and VCAM-1 indicating that the integri...

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Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11β-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.