Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

Doing Ethics in a Pluralistic World is an apt title for this collection of essays in honour of Roger C. Hutchinson who, over many decades, has encouraged and participated in shaping a Canadian contextual social ethics. His abiding interest in social ethics and in religious engagement with public issues is reflected in his life’s work — seeking the consensus and self-knowledge required to achieve cooperation in the search for a just, participatory, and sustainable society. One of Roger Hutchinson’s (...) many notable accomplishments is his development of a method of dialogue for ethical clarification in situations of diversity. Some of the essays collected here apply this method to specific issues, while others discuss how religious persons and organizations can and do co-operate in a pluralistic world to achieve social and ecological well-being. All essays are of keen interest to those concerned with the role and function of ethics at the matrix of religious conviction and social transformation. For nearly three decades Roger Hutchinson has been based at Victoria University in Toronto, first in religious studies, then at Emmanuel College, where he completed his teaching career as professor of church and society while serving as principal from 1996 to 2001. (shrink)

This chapter suggests that descriptive epidemiological studies like the Global Burden of Disease Study can usefully be divided into four tasks: describing individuals’ health states over time, assessing their health states under a range of counterfactual scenarios, summarizing the information collected, and then packaging it for presentation. The authors show that each of these tasks raises important and challenging ethical questions. They comment on some of the philosophical issues involved in measuring health states, attributing causes to health outcomes, choosing the (...) counterfactual against which to assess causes, aggregating and summarizing complex information across multiple domains, discounting, age-weighting, handling fetal deaths, measuring health inequalities, representing uncertainty, and assessing personal responsibility for health outcomes. (shrink)

Si le christianisme a survécu en Grande Syrie, c'est en raison de facteurs spécifiques: l'intégrité de la communauté chrétienne arabe indigène dans la région; l'intégration sociale des chrétiens arabes syriens dans la société musulmane; l'échec des musulmans dans le prosélytisme agressif auprès des chrétiens; l'identification ethnique de la population indigène avec les nouvelles arrivées du VIIe siècle. L'arabisation ne signifiait pas systématiquement l'islamisation. Elle encourageait même le contraire dans certaines régions comme la Palestine, coeur d'une Eglise chrétienne arabophone viable.

Originally published in 1944, this book presents the case for keeping examinations as part of the British school system. Brereton suggests potential reforms and argues that examinations have positive values in 'stimulating pupils and teachers generally, and in co-ordinating the work and aims of schools that might otherwise drift far apart'. This book will be of value to anyone with an interest in the debate surrounding the changing role of examinations in British education.

First published in 2003. Routledge is an imprint of Taylor & Francis, an informa company.