1 The antagonist dynamics of suramin were investigated at P21-receptors in isolated rings of endothelium-denuded ear artery from New Zealand White (NZW) rabbits. 2 a,,8-Methylene adenosine 5'-triphosphate (ATP) concentration-effect curves were constructed cumulatively in a paired curve design in the absence and presence of increasing concentrations of suramin, incubated for 45 min. The slope of the resulting Schild plot was significantly greater than unity (1.50 0.08). 3 Assuming that slow equilibration by suramin explains the steep Schild plot, further experiments were conducted using short (15 min) and long (3 h) incubation times. The resulting Schild plot slopes were 1.66 + 0.36 and 1.06 + 0.13 respectively confirming the assumption. However, after 3 h incubation, suramin also caused depression of a,,-methylene ATP curves. 4 In an attempt to minimize the depressant effect of suramin, a kinetic study was designed to calculate the minimum incubation times for each concentration of suramin used in the Schild analysis to achieve effectively complete equilibrium. Theoretically fractional occupancy for the antagonist is given by (r -1)/ r, where r is the dose-ratio. A plot of (r -1)/r against time allowed the apparent 'on' and 'off' rate constants to be calculated. 5 With the resulting rate constant estimates, an optimised antagonism study was carried out in which incubation times were chosen such that >95% occupancy by suramin could be achieved without agonist curve depression at each concentration of suramin used. 6 Under these conditions, suramin fulfilled all criteria for simple competition: parallel rightward displacement of a.B-methylene ATP curves and a Schild plot slope of unity (1.00 + 0.09). The resulting pKB estimate was 4.79 + 0.05. This estimate of affinity was shown to be independent of the agonist used in another experiment in which L-fy-methylene ATP was employed (pKB = 5.17).7 Under the same conditions, suramin was found to have no effect on KCI-induced contractions and only slight effects on phenylephrine-and histamine-induced responses. 8 This analysis provides the first evidence that suramin is a genuine competitive P21-receptor antagonist.
BackgroundFood insecurity underlies and compounds many of the development issues faced by remote Indigenous communities in Australia. Multi-sector approaches offer promise to improve food security. We assessed the feasibility of a novel multi-sector approach to enhance community food security in remote Indigenous Australia.MethodA longitudinal comparative multi-site case study, the Good Food Systems Good Food for All Project, was conducted (2009–2013) with four Aboriginal communities. Continuous improvement meetings were held in each community. Data from project documents and store sales were used to assess feasibility according to engagement, uptake and sustainability of action, and impact on community diet, as well as identifying conditions facilitating or hindering these.ResultsEngagement was established where: the community perceived a need for the approach; where trust was developed between the community and facilitators; where there was community stability; and where flexibility was applied in the timing of meetings. The approach enabled stakeholders in each community to collectively appraise the community food system and plan action. Actions that could be directly implemented within available resources resulted from developing collaborative capacity. Actions requiring advocacy, multi-sectoral involvement, commitment or further resources were less frequently used. Positive shifts in community diet were associated with key areas where actions were implemented.ConclusionA multi-sector participatory approach seeking continuous improvement engaged committed Aboriginal and non-Aboriginal stakeholders and was shown to have potential to shift community diet. Provision of clear mechanisms to link this approach with higher level policy and decision-making structures, clarity of roles and responsibilities, and processes to prioritise and communicate actions across sectors should further strengthen capacity for food security improvement. Integrating this approach enabling local decision-making into community governance structures with adequate resourcing is an imperative.
Nutritious, safe, affordable, and enjoyable food is a fundamental prerequisite for health. As a nation, Australia is currently classified as food secure with the domestic production exceeding domestic consumption of most major food groups. The domestic system is almost self-sufficient in terms of nutritious plant foods, although these foods have seen steady higher price increases relative to other foods, with nutrition equity implications. However, the viability of Australia's food security sits counter to the continued presence of a stable and supportive climate. This article reviews the current state of science concerning the interface between climate change, food systems, and human health to reveal the key issues that must be addressed if Australia is to advance human health and sustainable food systems under a changing climate.
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