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Huet O.,Heart and Diabetes Institute | Huet O.,University Paris - Sud | Dupic L.,University Paris - Sud | Harrois A.,University Paris - Sud | Duranteau J.,University Paris - Sud
Frontiers in Bioscience | Year: 2011

Endothelial activation and dysfunction play a key role in the pathogenesis of sepsis. During septic shock, endothelial dysfunction is involved in microcirculation impairment and organ dysfunction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have several potentially important effects on endothelial function and are implicated in physiological regulation and disease pathophysiology. The imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidants systems could induce endothelial dysfunction with alterations of vascular tone, increases in cell adhesion properties (leukocytes and platelet adhesion), increase in vascular wall permeability and a pro-coagulant state. Increasing evidence supports the idea that the principal cause of EC dysfunction during sepsis is cell injury. ROS and RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce both necrotic and apoptotic cell death. Understanding the mechanisms underlying the generation of ROS and RNS in endothelial cells and the causes of endothelial dysfunction in sepsis may help provide therapeutic strategies to tackle endothelial dysfunction and microcirculatory failure in sepsis.

Dickinson K.M.,CSIRO | Dickinson K.M.,University of Adelaide | Dickinson K.M.,National Health and Medical Research Council of Australia | Clifton P.M.,CSIRO | And 6 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Dietary salt is related to blood pressure (BP), and cardiovascular disease and increased sodium intakes have been shown to impair vascular function. The effect of salt on endothelial function postprandially is unknown. Objective: The aim was to investigate the postprandial effect of dietary salt on endothelial function as measured by flow-mediated dilatation (FMD) and peripheral arterial tonometry in healthy subjects. Design: Sixteen healthy, normotensive subjects received a meal with added salt (HSM; 65 mmol Na) and a control low-salt meal (LSM; 5 mmol Na) on 2 separate occasions in a randomized order. Endothelial function was measured while fasting and postprandially at 30, 60, 90, and 120 min by using FMD and reactive hyperemia peripheral arterial tonometry. BP was also measured. Results: Baseline FMD, reactive hyperemia index (RHI), and BP values were similar across interventions. Overall FMD was reduced 2 h postprandially. FMD was significantly more impaired after the HSM than after the LSM at 30 min [HSM (mean ± SD): 3.39 ± 2.44%; LSM: 6.05 ± 3.21%; P < 0.01] and at 60 min (HSM: 2.20 ± 2.77%; LSM: 4.64 ± 2.48%; P < 0.01). No significant differences in BP or RHI were observed between meals. Conclusions: An HSM, which reflects the typical amount of salt consumed in a commonly eaten meal, can significantly suppress brachial artery FMD within 30 min. These results suggest that high salt intakes have acute adverse effects on vascular dilatation in the postprandial state. This trial was registered at www.anzctr.org.au/trial-view. aspx?ID=335115 as ACTRN12610000124033. © 2011 American Society for Nutrition.

O'Hara B.J.,University of Sydney | Bauman A.E.,University of Sydney | Eakin E.G.,University of Queensland | King L.,University of Sydney | And 7 more authors.
Health Promotion Practice | Year: 2013

The Get Healthy Information and Coaching Service® (GHS), a free government-funded telephone-delivered information and coaching service was launched in February 2009 by the Australian New South Wales state government. It represents the translation of research evidence applied in the real world (T4 or Phase 4 translation), aimed at addressing the modifiable risk factors associated with the overweight and obesity. In controlled settings, it has been established that telephone-based lifestyle counseling programs are efficacious in reducing anthropometric and behavioral risk factors. This article presents the GHS case study as a population-wide intervention and describes the quasi-experimental evaluation framework used to evaluate both the process (statewide implementation) and impact (effectiveness) of the GHS in a real-world environment. It details the data collection, measures, and statistical analysis required in assessing the process of implementation-reach and recruitment, marketing and promotion, service satisfaction, intervention fidelity, and GHS setting up and operations costs-and in assessing the impact of GHS-increasing physical activity, improving dietary practices, and reducing body weight and waist circumference. The comprehensive evaluation framework designed for the GHS provides a method for building effectiveness evidence of a rare translation of efficacy trial evidence into population-wide practice. © 2012 Society for Public Health Education.

Villani A.M.,CSIRO | Villani A.M.,Flinders University | Clifton P.M.,CSIRO | Clifton P.M.,Heart and Diabetes Institute | And 2 more authors.
Journal of Human Nutrition and Dietetics | Year: 2012

Background: Hypertension is common in individuals with type 2 diabetes mellitus (T2DM). Dietary sodium plays an important regulatory role in blood pressure management. However, dietary sodium intakes and the major food sources of dietary sodium have yet to be thoroughly investigated in individuals with T2DM. Methods: In a cross-sectional study sample of 88 overweight and obese men (n=52) and women (n=36) with T2DM in Adelaide, Australia, sodium intake and excretion was investigated using two different methodologies, including a 4-day weighed food record and 24-h urinary sodium excretion. The major dietary contributors to sodium intake in this population were also explored. Results: Mean (SD) 24-h urinary sodium excretion was greater (P<0.001) in males [195.1(74.6)mmol] compared to females [144.3(41.8)mmol]. Breads and cereals (B&Cs) were the largest contributors to dietary sodium intake (23% of intake). There was an association between sodium intake from B&Cs and 24-h urinary sodium excretion (r=0.235; P=0.02); however, when controlled for gender, B&Cs were not associated with urinary sodium excretion (males, r=0.134; P=0.343; females, r=0.102; P=0.554). Conclusions: The findings of the present study show that sodium intake and excretion in individuals with T2DM is more than two-fold greater than the current recommendations for chronic disease prevention. B&Cs were the major dietary contributors of sodium intake, suggesting that they are primary targets for a reduction in their sodium content. © 2012 The Authors. Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

Colagiuri S.,University of Sydney | Lee C.M.Y.,University of Sydney | Wong T.Y.,University of Melbourne | Wong T.Y.,Singapore Eye Research Institute | And 5 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - To re-evaluate the relationship between glycemia and diabetic retinopathy. RESEARCH DESIGN AND METHODS - We conducted a data-pooling analysis of nine studies from five countries with 44,623 participants aged 20-79 years with gradable retinal photographs. The relationship between diabetes-specific retinopathy (defined as moderate or more severe retinopathy) and three glycemic measures (fasting plasma glucose [FPG; n = 41,411], 2-h post oral glucose load plasma glucose [2-h PG; n=21,334], and A1C [n=28,010]) was examined. RESULTS - When diabetes-specific retinopathy was plotted against continuous glycemic measures, a curvilinear relationship was observed for FPG and A1C. Diabetes-specific retinopathy prevalence was low for FPG <6.0 mmol/l and A1C <6.0% but increased above these levels. Based on vigintile (20 groups with equal numbers) distributions, glycemic thresholds for diabetes-specific retinopathy were observed over the range of 6.4-6.8 mmol/l for FPG, 9.8 -10.6 mmol/l for 2-h PG, and 6.3-6.7% for A1C. Thresholds for diabetes-specific retinopathy from receiver-operating characteristic curve analyses were 6.6 mmol/l for FPG, 13.0 mmol/l for 2-h PG, and 6.4% for A1C. CONCLUSIONS - This study broadens the evidence based on diabetes diagnostic criteria. A narrow threshold range for diabetes-specific retinopathy was identified for FPG and A1C but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/l and that an A1C of 6.5% is a suitable alternative diagnostic criterion. © 2011 by the American Diabetes Association.

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