Evening aspirin intake results in higher levels of platelet inhibition and a reduction in reticulated platelets - a window of opportunity for patients with cardiovascular disease?

Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B2 (sTxB2) levels, the Platelet Function Analyzer (PFA)-200® Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow®), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB2 levels were the lowest after OD-evening in comparison with OD-morning (p = <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p = .01) and BID (p = .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk.

Setting conservation management thresholds using a novel participatory modeling approach.

We devised a participatory modeling approach for setting management thresholds that show when management intervention is required to address undesirable ecosystem changes. This approach was designed to be used when management thresholds: must be set for environmental indicators in the face of multiple competing objectives; need to incorporate scientific understanding and value judgments; and will be set by participants with limited modeling experience. We applied our approach to a case study where management thresholds were set for a mat-forming brown alga, Hormosira banksii, in a protected area management context. Participants, including management staff and scientists, were involved in a workshop to test the approach, and set management thresholds to address the threat of trampling by visitors to an intertidal rocky reef. The approach involved trading off the environmental objective, to maintain the condition of intertidal reef communities, with social and economic objectives to ensure management intervention was cost-effective. Ecological scenarios, developed using scenario planning, were a key feature that provided the foundation for where to set management thresholds. The scenarios developed represented declines in percent cover of H. banksii that may occur under increased threatening processes. Participants defined 4 discrete management alternatives to address the threat of trampling and estimated the effect of these alternatives on the objectives under each ecological scenario. A weighted additive model was used to aggregate participants' consequence estimates. Model outputs (decision scores) clearly expressed uncertainty, which can be considered by decision makers and used to inform where to set management thresholds. This approach encourages a proactive form of conservation, where management thresholds and associated actions are defined a priori for ecological indicators, rather than reacting to unexpected ecosystem changes in the future.

Specific effect of haloperidol on dopamine turnover in the frontal cortex.

A single injection of haloperidol (0.08 mg/kg) produced marked increases in HVA in rabbit brain. Of the dopamine-containing areas studied, the elevation of HVA was significantly greater in the frontal cortex than in the striatum, the tuberculum olfactorium or the parietal cortex. After chronic treatment, a tolerance phenomenon to the effects of haloperidol on HVA was observed only in the striatal and limbic areas. The present results suggest that the frontal cortex may be a preferential target for the antipsychotic activity of neuroleptic agents.

Tissue fractionation and catecholamines--IV. Adenosine triphosphatase in chromaffin granules: a distribution artefact.

Tissue fractionation was used as an analytical tool to study the subcellular distribution of an adenosine triphosphatase activated by Mg2+ in adrenal medullae of the pig and ox and in whole adrenals of the rat. By measuring adenosine triphosphatase and various enzymes in the fractions obtained by differential centrifugation, the distribution pattern of adenosine triphosphatase was found to differ markedly from that of markers like catecholamines, dopamine beta-hydroxylase or cytochrome oxidase. In the pig and ox the distribution of inosine diphosphatase paralleled that of adenosine triphosphatase. After equilibration through sucrose density gradients, no adenosine triphosphatase activity was detected in the chromaffin granules in the rat. However, in bovine adrenal medullae, a large part of the adenosine triphosphatase activity equilibrated in that area of the gradient in which the chromaffin granules were found. This adenosine triphosphatase distribution pattern was an artefact produced by applying a too concentrated sample to the gradient. When a more diluted sample of bovine tissue was used no adenosine triphosphatase activity was found to be associated with the chromaffin granules. The present results lead to a reconsideration of the role of the adenosine triphosphatase in some processes in which the chromaffin granules are involved. Moreover, the degree of purity of many chromaffin granule preparations is again questioned.