Microabrasion : A novel method to assess surface degradation of UHMWPE following sterilisation and ageing

The ageing behaviour of ultra-high molecular weight polyethylene (UHMWPE) has been studied following gamma irradiation (25 or 40 kGy) in air. Accelerated ageing procedures used elevated temperature (70°C) and/or pressurised oxygen (5 bar). Shelf-aged UHMWPE was also studied. The variation in surface density and mechanical properties were determined following the various sterilisation and ageing treatments. Microabrasive wear testing was also performed. Wear rates were found to correlate well with stress at break for sterilised and aged UHMWPE but not with elongation to failure. It is proposed that the wear mechanism is fracture dominated and occurs following some disentanglement of the polymer chains. Wear also depends upon embrittlement of the surface layer due to its processing and ageing. Elongation to failure in a tensile test is not a good measure of this embrittlement whereas the microabrasion test provides more surface sensitive information concerning this property.

Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid

The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu(8)/ Abu(2) (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu(8))GLP-1 was completely stable to human plasma (half-life > 12h), GLP-1, GIP, and (Abu(2))GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu(8))GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu(2))GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu(8))GLP-1 displayed substantial glucose-lowering and insulin -releasing activities, whereas (Abu(2))GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala(8)/Ala(2) substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu(8))GLP-1 represents a potential candidate for future therapeutic development. (C) 2004 Elsevier Inc. All rights reserved.