The role of glucocorticoids in the induction of zinc-α2-glycoprotein expression in adipose tissue in cancer cachexia

Loss of adipose tissue in cancer cachexia in mice bearing the MAC16 tumour arises from an increased lipid mobilisation through increased expression of zinc-α2-glycoprotein (ZAG) in white (WAT) and brown (BAT) adipose tissue. Glucocorticoids have been suggested to increase ZAG expression, and this study examines their role in cachexia and the mechanisms involved. In mice bearing the MAC16 tumour, serum cortisol concentrations increased in parallel with weight loss, and the glucocorticoid receptor antagonist RU38486 (25 mg kg-1) attenuated both the loss of body weight and ZAG expression in WAT. Dexamethasone (66 μg kg-1) administration to normal mice produced a six-fold increase in ZAG expression in both WAT and BAT, which was also attenuated by RU38486. In vitro studies using 3T3-L1 adipocytes showed dexamethasone (1.68 μM) to stimulate lipolysis and increase ZAG expression, and both were attenuated by RU38486 (10 μM), anti-ZAG antibody (1 μ gml-1), and the β3-adrenoreceptor (β3-AR) antagonist SR59230A (10 μM). Zinc-α2-glycoprotein also increased its own expression and this was attenuated by SR59230A, suggesting that it was mediated through the β3-AR. This suggests that glucocorticoids stimulate lipolysis through an increase in ZAG expression, and that they are responsible for the increase in ZAG expression seen in adipose tissue of cachectic mice. © 2005 Cancer Research UK.

Organizational resources enabling service responsiveness:evidence from Greece

This article examines the implementation of relationship marketing strategy based on a sample of business-to-business firms operating in Greece. Organizational resources, including a focus on learning and flexibility/adaptation in strategic planning, are demonstrated to be antecedents of effective relationship marketing strategies. The possession of these resources lead to superior customer performance (as measured by customer satisfaction and loyalty) and, ultimately, superior financial performance (as measured by profit levels, profit margin, and ROI). Our results provide support for the development of organizational resources that foster and enable relationship marketing in business-to-business environments since such resources are linked with improved firm performance. © 2003 Elsevier Inc. All rights reserved.

Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic ß-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 µm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100-1000 µm) increased (1.3-1.5-fold; p

The MacDQoL individualized measure of the impact of macular degeneration on quality of life: reliability and responsiveness

PURPOSE: To investigate the MacDQoL test-retest reliability and sensitivity to change in vision over a period of one year in a sample of patients with age-related macular degeneration (AMD). DESIGN: A prospective, observational study. METHOD: Patients with AMD from an ophthalmologist's list (n = 135) completed the MacDQoL questionnaire by telephone interview and underwent a vision assessment on two occasions, one year apart. RESULTS: Among participants whose vision was stable over one year (n = 87), MacDQoL scores at baseline and follow-up were highly correlated (r = 0.95; P < .0001). Twelve of the 22 scale items had intraclass correlations of >.80; only two were correlated <.7. There was no difference between baseline and follow-up scores (P = .85), indicating excellent test-retest reliability. Poorer quality of life (QoL) at follow-up, measured by the MacDQoL present QoL overview item, was associated with deterioration in both the better eye and binocular distance visual acuity [VA] (r = 0.29; P = .001, r = 0.21; P = .016, respectively; n = 135). There was a positive correlation between deterioration in the Mac. DQoL average weighted impact score and deterioration in both binocular near VA and reading speed (r = 0.20; P = .019, r = 0.18; P = .041, respectively; n = 135). CONCLUSION: The MacDQoL has excellent test-retest reliability. Its sensitivity to change in vision status was demonstrated in correlational analyses. The measure indicates that the negative impact of AMD on QoL increases with increasing severity of visual impairment.

Vascular cell responsiveness to toll-like receptor ligands in carotid atheroma

Background Atherosclerosis is potentiated by stimulation of Toll-like receptors (TLRs), which serve to detect pathogen associated molecular patterns (PAMPs). However little is known of which PAMPs may be present in atheroma, or capable of stimulating inflammatory signalling in vascular cells. Materials and Methods DNA extracted from human carotid atheroma samples was amplified and sequenced using broad-range 16S gene specific primers to establish historical exposure to bacterial PAMPs. Responsiveness of primary human arterial and venous endothelial and smooth muscle cells to PAMPs specific for each of the TLRs was assessed by measurement of interleukin-8 secretion and E-selectin expression. Results Extracts of atheromatous tissue stimulated little or no signalling in TLR-transfected HEK-293 cells. However, sequencing of bacterial DNA amplified from carotid atheroma revealed the presence of DNA from 17 different bacterial genera, suggesting historical exposure to bacterial lipopeptide, lipopolysaccharide and flagellin. All cells examined were responsive to the ligands of TLR3 and TLR4, poly inosine:cytosine and lipopolysaccharide. Arterial cells were responsive to a wider range of PAMPs than venous cells, being additionally responsive to bacterial flagellin and unmethylated cytosine-phosphate-guanosine DNA motifs, the ligands of TLR5 and TLR9, respectively. Cells were generally unresponsive towards the ligands of human TLR7 and TLR8, loxoribine and single stranded RNA. Only coronary artery endothelial cells expressed TLR2 mRNA and responded to the TLR2 ligand Pam3CSK4. Conclusions Vascular cells are responsive to a relatively diverse range of TLR ligands and may be exposed, at least transiently, to ligands of TLR2, TLR4, TLR5 and TLR9 during the development of carotid atheroma.

Evacuation responsiveness by government organisations (ERGO):the evacuation preparedness assessment workbook

This Evacuation Preparedness Assessment Workbook (EPAW) is a tool to assess the level of preparedness of Government Organisations (GOs) for the mass evacuation of their public. It has its origins in the results of a three-year, EU-funded research project called Evacuation Preparedness by Government Organisations (ERGO) which sought to research and strengthen the preparedness activities for the evacuation of cities, regions or even countries. This EPAW presents a list of tasks to be carried out at the different phases of evacuation preparedness. It also provides an assessment facility to evaluate how much progress GOs have made against each task, as well as indications of standard and best practices for each task. A brief background to the need for evacuation, the ERGO project and the development of the workbook is given next. After this, the application process of the workbook is explained and illustrated with an example.

Acute and long-term effects of peroxisome proliferator-activated receptor-γ activation on the function and insulin secretory responsiveness of clonal beta-cells

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2-100 M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 M) enhanced (p

Growth, uniformity, local responsiveness, and system-wide adaptation in multiunit franchising

Using the resource-based view framework, we investigate the link between multiunit franchising (MUF) and performance on four key challenges in franchise chain management: growth, uniformity, local responsiveness, and system-wide adaptation. Our findings support the assertion that system growth is positively related to MUF rate within a system, in particular in relation to geographic expansion. Interestingly, while uniformity does not seem to be related to MUF rate, we find marginal support for an inverted u-shaped relationship between system-wide adaptation and MUF rate. Furthermore, the data suggest that local responsiveness and MUF rate are related in a u-shaped function.