Perilli E.,Flinders University |
Cantley M.,University of Adelaide |
Marino V.,University of Adelaide |
Crotti T.N.,University of Adelaide |
And 4 more authors.
Scandinavian Journal of Immunology | Year: 2015
In rodent models of inflammatory arthritis, bone erosion has been non-invasively assessed by micro-computed tomography (micro-CT). However, non-invasive assessments of paw swelling (oedema) are still based on clinical grading by visual evaluation, or measurements by callipers, not always reliable for the tiny mouse paws. The aim of this work was to demonstrate a novel straightforward 3D micro-CT analysis protocol capable of quantifying not only joint bone erosion, but also soft tissue swelling, from the same scans, in a rodent inflammatory arthritis model. Balb/c mice were divided into two groups: collagen antibody-induced arthritis (CAIA) and CAIA treated with prednisolone, the latter reflecting an established treatment in human rheumatoid arthritis. Clinical paw scores were recorded. On day 10, front paws were assessed by micro-CT and histology. Micro-CT measurements included paw volume (bone and soft tissue together) and bone volume at the radiocarpal joint, and bone volume from the radiocarpal to the metacarpophalangeal joint. Micro-CT analysis revealed significantly lower paw volume (-36%, P < 0.01) and higher bone volume (+17%, P < 0.05) in prednisolone-treated CAIA mice compared with untreated CAIA mice. Paw volume and bone volume assessed by micro-CT correlated significantly with clinical and histological scores (|r| > 0.5, P < 0.01). Untreated CAIA mice showed significantly higher clinical scores, higher inflammation levels histologically, cartilage and bone degradation, and pannus formation, compared with treated mice (P < 0.01). The presented novel micro-CT analysis protocol enables 3D-quantification of paw swelling at the micrometre level, along with the typically assessed bone erosion, using the same images/scans, without altering the scanning procedure or using contrast agents. © The Authors.
Dharmapatni A.A.S.S.K.,University of Adelaide |
Cantley M.D.,University of Adelaide |
Marino V.,University of Adelaide |
Perilli E.,Flinders University |
And 4 more authors.
Mediators of Inflammation | Year: 2015
Objective. To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice. Methods. Four groups of mice (n = 6 per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells. Results. Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores (P < 0.05) and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 (P < 0.05) and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice. Conclusion. Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss. © 2015 Anak A. S. S. K. Dharmapatni et al.
Abu-Sneineh A.,Royal Adelaide Hospital |
Tam W.,Royal Adelaide Hospital |
Schoeman M.,Royal Adelaide Hospital |
Schoeman M.,University of Adelaide |
And 9 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2010
Background Acid reflux is often difficult to control medically. Aim To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). Methods Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. Results At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. Conclusions High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation. © 2010 Blackwell Publishing Ltd.
Doughty R.N.,University of Auckland |
Whalley G.A.,University of Auckland |
Whalley G.A.,Middlemore Hospital |
Gamble G.D.,University of Auckland |
And 142 more authors.
Journal of Hypertension | Year: 2011
Background: The Action in Diabetes and Vascular Disease (ADVANCE) Study demonstrated that a fixed combination of perindopril and indapamide reduced the risk of major vascular events and mortality in patients with type 2 diabetes. This Echocardiographic Substudy was designed to determine the effects of this treatment on left ventricular diastolic function and left ventricular mass. Methods: Five hundred and fifty-five patients entering ADVANCE underwent quantitative echocardiography prior to randomization and after 6 months and 4 years of treatment with perindopril-indapamide or placebo. Main end points were left ventricular diastolic function (ratio of mitral E velocity/early medial mitral annular tissue Doppler velocity, E/Em, and left atrial volume index) and left ventricular mass index. Results: Overall, blood pressure was reduced in the perindopril-indapamide group compared with placebo. E/Em and left atrial volume index both increased over the 4 years. There was no effect of perindopril-indapamide on E/Em, although there was a small attenuation of the increase in left atrial volume index with active treatment. Left ventricular mass index was reduced by 2.7 g/m with active treatment (95% confidence interval -5.0 to -0.1, P = 0.04). Conclusion: Compared with placebo, the perindopril-indapamide combination reduced blood pressure and left ventricular mass in patients with diabetes, but did not improve left ventricular diastolic function. Left ventricular diastolic function worsened in both groups over 4 years, despite blood pressure reduction and reduction in left ventricular mass. Improving left ventricular diastolic function remains a challenge in patients with diabetes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Walls H.L.,Monash University |
Peeters A.,Monash University |
Proietto J.,Repatriation Hospital |
McNeil J.J.,Monash University
BMC Public Health | Year: 2011
Background: Controlling obesity has become one of the highest priorities for public health practitioners in developed countries. In the absence of safe, effective and widely accessible high-risk approaches (e.g. drugs and surgery) attention has focussed on community-based approaches and social marketing campaigns as the most appropriate form of intervention. However there is limited evidence in support of substantial effectiveness of such interventions. Discussion. To date there is little evidence that community-based interventions and social marketing campaigns specifically targeting obesity provide substantial or lasting benefit. Concerns have been raised about potential negative effects created by a focus of these interventions on body shape and size, and of the associated media targeting of obesity. Summary. A more appropriate strategy would be to enact high-level policy and legislative changes to alter the obesogenic environments in which we live by providing incentives for healthy eating and increased levels of physical activity. Research is also needed to improve treatments available for individuals already obese. © 2011 Walls et al; licensee BioMed Central Ltd.
Condon J.,Repatriation Hospital |
Corkindale C.,University of South Australia |
Boyce P.,University of Sydney |
Gamble E.,University of South Australia
Journal of Reproductive and Infant Psychology | Year: 2013
Objective: Using data from the Australian First-Time Fathers Study, this article investigates the relationship between a father's antenatal attachment to his foetus and his subsequent attachment to his infant at 6 and 12 months postnatally. Method: 204 first-time expectant fathers were assessed, and subsequently reassessed at 6 and 12 months postpartum on a large number of measures (including attachment). Results: Findings highlight the strong continuity of attachment across these three assessment points, as well as the important influence of the man's partner relationship and mental well-being on his attachment. Conclusion: Pregnancy provides a potential window of opportunity for enhancing antenatal attachment in expectant fathers, with potential long-term benefits for the future father-child relationship. © 2013 Copyright Society for Reproductive and Infant Psychology.