16 research outputs found
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Protein kinase C delta mediates cerebral reperfusion injury in vivo
Protein kinase C (PKC) has been implicated in mediating ischemic and reperfusion damage in multiple organs. However, conflicting reports exist on the role of individual PKC isozymes in cerebral ischemic injury. Using a peptide inhibitor selective for deltaPKC, deltaV1-1, we found that deltaPKC inhibition reduced cellular injury in a rat hippocampal slice model of cerebral ischemia [oxygen-glucose deprivation (OGD)] when present both during OGD and for the first 3 hr of reperfusion. We next demonstrated peptide delivery to the brain parenchyma after in vivo delivery by detecting biotin-conjugateddeltaV1-1 and by measuring inhibition of intracellular deltaPKC translocation, an indicator of deltaPKC activity. Delivery of deltaV1-1 decreased infarct size in an in vivo rat stroke model of transient middle cerebral artery occlusion. Importantly, deltaV1-1 had no effect when delivered immediately before ischemia. However, delivery at the onset, at 1 hr, or at 6 hr of reperfusion reduced injury by 68, 47, and 58%, respectively. Previous work has implicated deltaPKC in mediating apoptotic processes. We therefore determined whether deltaPKC inhibition altered apoptotic cell death or cell survival pathways in our models. We found that deltaV1-1 reduced numbers of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells, indicating decreased apoptosis, increased levels of phospho-Akt, a kinase involved in cell survival pathways, and inhibited BAD (Bcl-2-associated death protein) protein translocation from the cell cytosol to the membrane, indicating inhibition of proapoptotic signaling. These data support a deleterious role for deltaPKC during reperfusion and suggest that deltaV1-1 delivery, even hours after commencement of reperfusion, may provide a therapeutic advantage after cerebral ischemia
Ethics and advance care planning in a culturally diverse society
Emerging international research suggests that in multicultural countries, such as Australia and the United States, there are significant disparities in end-of-life care planning and decision making by people of minority ethnic backgrounds compared with members of mainstream English-speaking background populations. Despite a growing interest in the profound influence of culture and ethnicity on patient choices in end-of-life care, and the limited uptake of advance care plans and advance directives by ethnic minority groups in mainstream health care contexts, there has been curiously little attention given to cross-cultural considerations in advance care planning and end-of-life care. Also overlooked are the possible implications of cross-cultural considerations for nurses, policy makers, and others at the forefront of planning and providing end-of-life care to people of diverse cultural and language backgrounds. An important aim of this article is to redress this oversight.<br /