N-terminally modified glucagon-like peptide-1(7-36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activity in vivo

Glucagon-like peptide-1 (7-36)amide (tGLP-1) is inactivated by dipeptidyl peptidase (DPP) IV by removal of the NH2-terminal dipeptide His(7)-Ala(8). We examined the degradation of NH2-terminally modified His(7)-glucitol tGLP-1 and its insulin-releasing and antihyperglycaemic activity in vivo, tGLP-1 was degraded by purified DPP IV after 4 h (43% intact) and after 12 hi 89% was converted to GLP-1(9-36)amide. In contrast > 99% of His(7)-glucitol tGLP-1 remained intact at 12 h. His(7)-glucitol tGLP-1 was similarly resistant to plasma degradation in vitro. His7-glucitol tGLP-1 showed greater resistance to degradation in vivo (92% intact) compared to tGLP-1 (27% intact) 10 min after i.p. administration to Wistar rats. Glucose homeostasis was examined following i.p. injection of both peptides (12 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly reduced and insulin concentrations elevated following peptides administration compared with glucose alone. The area under the curve (AUC) for glucose for controls (AUC 691 +/- 35 mM/min) was significantly lower after administration of tGLP-1 and His7-glucitol tGLP-1 (36 and 49% less; AUC; 440 +/- 40 and 353 +/- 31 mM/min, respectively; P

The response of macrophages to particles of resorbable polymers and their degradation products

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E-2 (PGE(2)) and interleukin-1 alpha IL-1alpha was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1alpha and PGE(2) release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1alpha and PGE(2) release. The lactate and glycolate monomers did not increase PGE(2) or IL-1alpha release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form. (C) 2003 Kluwer Academic Publishers.

Parametric and non-parametric estimates of willingness to pay for forest recreation in Northern Ireland: A discrete choice contingent valuation study with follow-ups

In this study we show that forest areas contribute significantly to the estimated benefits from om outdoor recreation in Northern Ireland. Secondly we provide empirical evidence of the gains in the statistical efficiency of both benefit and parameter estimates obtained by analysing follow-up responses with Double Bounded interval data analysis. As these gains are considerable, it is clearly worth considering this method in CVM survey design even when moderately large sample sizes are used. Finally we demonstrate that estimates of means and medians of WTP distributions for access to forest recreation show plausible magnitude, are consistent with previous UK studies, and converge across parametric and non-parametic methods of estimation.

Decadence in the Forest: Smyth's Der Wald in its Critical Context

Ethel Smyth’s opera, Der Wald, met with mixed reactions at its premiere in Berlin in 1902. Many factors contributed to this, not least, as Smyth herself observed, anti-British sentiment in Germany following the second Boer War. One might have expected that the reception of the opera at its British premiere on 18 July at Covent Garden might have been more positive, but even here critical opinion was divided. Even positive reviews were not free from gender discrimination, and other reviews condemned the opera for being too German or Wagnerian. What was meant by ‘Wagnerian’? This article answers the question in three ways. Firstly, I argue that ‘Wagnerian’ meant not a leitmotif-filled, through-composed work (as distinct from a number opera), but simply a lyrical drama; for British audiences the model for this was Tannhäuser or Lohengrin, not the Ring or Tristan. Secondly, taking this definition on board, I analyse the musical language of the opera, in particular the key structure. The central duet sung by the doomed lovers, Heinrich and Röschen, is in F major, almost the furthest possible distance from the home key of the opera (E major), which characterizes the forest and ‘nature’ in general; by contrast, the next scene, where the Kundry-like Iolanthe attempts to seduce Heinrich (a crucial reversal of the more conventional power relations of the love duet), sees a return to the home key. Thirdly, I set the hermeneutical implications of this reversal in the context of the decadent movement, with which late nineteenth-century Wagnerism was associated, and which, following the conviction of Oscar Wilde in 1895, was discredited. Der Wald thus failed because of its ‘guilt by association’ with an aesthetic that had fallen into disrepute.

Electron-beam treatment of poly(lactic acid) to control degradation profiles

Bioresorbable polymers such as polylactide (PIA) and polylactide-co-glycolide (PLGA) have been used successfully as biomaterials in a wide range of medical applications. However, their slow degradation rates and propensity to lose strength before mass have caused problems. A central challenge for the development of these materials is the assurance of consistent and predictable in vivo degradation. Previous work has illustrated the potential to influence polymer degradation using electron beam (e-beam) radiation. The work addressed in this paper investigates further the utilisation of e-beam radiation in order to achieve a more surface specific effect. Variation of e-beam energy was studied as a means to control the effective penetrative depth in poly-L-lactide (PLEA). PLEA samples were exposed to e-beam radiation at individual energies of 0.5 MeV, 0.75 MeV and 1.5 MeV. The near-surface region of the PLEA samples was shown to be affected by e-beam irradiation with induced changes in molecular weight, morphology, flexural strength and degradation profile. Moreover, the depth to which the physical properties of the polymer were affected is dependent on the beam energy used. Computer modelling of the transmission of each e-beam energy level used corresponded well with these findings. (C) 2010 Elsevier Ltd. All rights reserved.

Temporal Variability in Predator-Prey Relationships of a Forest Floor Food Web

Connectance webs represent the standard data description in food web ecology, but their usefulness is often limited in understanding the patterns and processes within ecosystems. Increasingly, efforts have been made to incorporate additional, biologically meaningful, data into food web descriptions, including the construction of food webs using data describing the body size and abundance of each species. Here, data from a terrestrial forest floor food web, sampled seasonally over a 1-year period, were analysed to investigate (i) how stable the body size abundance and predator prey relationships of an ecosystem are through time and (ii) whether there are system-specific differences in body size abundance and predator prey relationships between ecosystem types.