Evaluation of glycated glucagon-like peptide-1(7-36)amide in intestinal tissue of normal and diabetic animal models

Glucagon-like peptide-1(7-36)amide (tGLP-1) is an important insulin-releasing hormone of the enteroinsular axis which is secreted by endocrine L-cells of the small intestine following nutrient ingestion. The present study has evaluated tGLP-1 in the intestines of normal and diabetic animal models and estimated the proportion present in glycated form. Total immunoreactive tGLP-1 levels in the intestines of hyperglycaemic hydrocortisone-treated rats, streptozotocin-treated mice and ob/ob mice were similar to age-matched controls. Affinity chromatographic separation of glycated and non-glycated proteins in intestinal extracts followed by radioimmunoassay using a fully crossreacting anti-serum demonstrated the presence of glycated tGLP-1 within the intestinal extracts of all control animals (approximately 19%., of total tGLP-1 content). Chemically induced and spontaneous animal models of diabetes were found to possess significantly greater levels of glycated tGLP-1 than controls, corresponding to between 24-71% of the total content. These observations suggest that glycated tGLP-1 may be of physiological significance given that such N-terminal modification confers resistance to DPP IV inactivation and degradation, extending the very short half-life (

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

In vitro testing of Advanced JAX (TM) Bone Void Filler System: species differences in the response of bone marrow stromal cells to beta tri-calcium phosphate and carboxymethylcellulose gel

The Advanced JAX (TM) Bone Void Filler System (AJBVFS) is a novel bone graft material manufactured by Smith and Nephew Orthopaedics Ltd. and comprises beta tri-calcium phosphate granules with carboxymethylcellulose (CMC) gel as a handling agent. This study investigated the potential, in vitro, of the AJBVFS to function as a delivery system for cell therapy to enhance healing of bone defects. The attachment of rabbit bone marrow stromal cells (rbBMSCs), human BMSCs (hBMSCs) and human bone-derived cells (hBDCs) to JAX (TM) granules and the effect of CMC gel on cell proliferation and differentiation were investigated. There were slight species differences in the number and morphology of cells attached on the JAX (TM) granules with less rbBMSC attachment than human. All cells tolerated the presence of CMC gel and a reduction in cell number was only seen after longer exposure to higher gel concentrations. Low concentrations of CMC gel enhanced proliferation, alkaline phosphatase (ALP) expression and ALP activity in human cells but had no effect on rbBMSC. This study suggests that AJBVFS is an appropriate scaffold for the delivery of osteogenic cells and the addition of CMC gel as a handling agent promotes osteogenic proliferation and differentiation and is therefore likely to encourage bone healing.

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.

Testing bone substitutes in a small animal model of revision arthroplasty

This study evaluated a modification of the rat-pin model to enable testing of bone substitute materials. The model was characterized using the ceramic, beta-tricalcium phosphate (betaTCP) as a filler.

The feeding dynamics of broiler chickens

Contrary to a commonly held belief that broiler chickens need more space, there is increasing evidence that these birds are attracted to other birds. Indeed, commercially farmed birds exhibit a range of socially facilitated behaviours, such as increased feeding and preening in response to the presence of other birds. Social facilitation can generate feedback loops, whereby the adoption of a particular behaviour can spread rapidly and suddenly through the population. Here, by measuring the rate at which broiler chickens join and leave a feeding trough as a function of the number of birds already there, we quantify social facilitation. We use these measurements to parameterize a simulation model of chicken feeding behaviour. This model predicts, and further observations of broiler chickens confirm, that social facilitation leads to excitatory and synchronized patterns of group feeding. Such models could prove a powerful tool in understanding how feeding patterns depend on broiler house design.

Recent advances in the analysis of behavioural organization and interpretation as indicators of animal welfare

While the incorporation of mathematical and engineering methods has greatly advanced in other areas of the life sciences, they have been under-utilized in the field of animal welfare. Exceptions are beginning to emerge and share a common motivation to quantify 'hidden' aspects in the structure of the behaviour of an individual, or group of animals. Such analyses have the potential to quantify behavioural markers of pain and stress and quantify abnormal behaviour objectively. This review seeks to explore the scope of such analytical methods as behavioural indicators of welfare. We outline four classes of analyses that can be used to quantify aspects of behavioural organization. The underlying principles, possible applications and limitations are described for: fractal analysis, temporal methods, social network analysis, and agent-based modelling and simulation. We hope to encourage further application of analyses of behavioural organization by highlighting potential applications in the assessment of animal welfare, and increasing awareness of the scope for the development of new mathematical methods in this area.

Interactions of the 67 kDa laminin receptor and its precursor with laminin

The 67LR (67 kDa laminin receptor) enables cells to interact with components of the extracellular matrix The molecule is derived from the 37LRP (37 kDa laminin receptor precursor); however, the precise molecular mechanism of this conversion is unknown. Recombinant 37LRP expressed in and purified from Escherichia colt, bound to human laminin in a SPR (surface plasmon resonance) experiment. 67LR isolated from human breast-cancer-derived cells in culture was also shown to bind to laminin by SPR. However, the kinetics of association are qualitatively different. 37LRP but not 67LR, binds to heparan sulfate. The binding of 37LRP to heparan sulfate did not affect the interaction of 37LRP with laminin In contrast, heparan sulfate reduces the extent of binding of laminin to 67LR. Taken together, these results show that 37LRP has some of the biological activities of 67LR, even prior to the conversion event. However, the conversion affects the sites of interaction with both laminin and heparan sulfate.

Food-web structure in low- and high-dimensional trophic niche spaces

A question central to modelling and, ultimately, managing food webs concerns the dimensionality of trophic niche space, that is, the number of independent traits relevant for determining consumer-resource links. Food-web topologies can often be interpreted by assuming resource traits to be specified by points along a line and each consumer's diet to be given by resources contained in an interval on this line. This phenomenon, called intervality, has been known for 30 years and is widely acknowledged to indicate that trophic niche space is close to one-dimensional. We show that the degrees of intervality observed in nature can be reproduced in arbitrary-dimensional trophic niche spaces, provided that the processes of evolutionary diversification and adaptation are taken into account. Contrary to expectations, intervality is least pronounced at intermediate dimensions and steadily improves towards lower- and higher-dimensional trophic niche spaces.

WASP-37b: A 1.8 M J Exoplanet Transiting a Metal-poor Star

We report on the discovery of WASP-37b, a transiting hot Jupiter orbiting an m v = 12.7 G2-type dwarf, with a period of 3.577469 ± 0.000011 d, transit epoch T 0 = 2455338.6188 ± 0.0006 (HJD; dates throughout the paper are given in Coordinated Universal Time (UTC)), and a transit duration 0.1304+0.0018 –0.0017 d. The planetary companion has a mass M p = 1.80 ± 0.17 M J and radius R p = 1.16+0.07 –0.06 R J, yielding a mean density of 1.15+0.12 –0.15 ?J. From a spectral analysis, we find that the host star has M sstarf = 0.925 ± 0.120 M sun, R sstarf = 1.003 ± 0.053 R sun, T eff = 5800 ± 150 K, and [Fe/H] = –0.40 ± 0.12. WASP-37 is therefore one of the lowest metallicity stars to host a transiting planet.