99 resultados para Neuronal Death


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Critical analysis of the High Court decision in Barns v Barns - relationship between mutual wills and testator family maintenance legislation - whether an agreement for mutual wills was void for public policy reasons - whether property of a deceased that was obligated under maintenance legislation could be passed to an applicant contrary to the mutual wills agreement - implications of decision.

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Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.

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The collapse of the peace process has seen Aceh return to a cycle of violence

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Zn and DHA have putative neuroprotective effects and these two essential nutrients are known to interact biochemically. We aimed to identify novel protein candidates that are differentially expressed in human neuronal cell line M17 in response to Zn and DHA that would explain the molecular basis of this interaction. Two-dimensional gel electrophoresis and MS were applied to identify major protein expression changes in the protein lysates of human Ml7 neuronal cells that had been grown in the presence and absence of Zn and DHA. Proteomic findings were further investigated using Western immunoblot and real-time PCR analyses. Four protein spots, which had significant differential expression, were identified and selected for in-gel trypsin digestion followed by matrix-assisted laser desorption ionisation MS analysis. The resultant peptide mass fingerprint for each spot allowed their respective identities to be deduced. Two human histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the presence of Zn (physiological condition). These proteomic findings were further supported by Western immunoblot and real-time PCR analyses using H3- and H4-specific monoclonal antibodies and oligonucleotide primers, respectively. We propose that dietary Zn and DHA cause a global effect on gene expression, which is mediated by histones. Such novel information provides possible clues to the molecular basis of neuroprotection by Zn and DHA that may contribute to the future treatment, prevention and management of neurodegenerative diseases such as Alzheimer's disease.

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The first purpose of this study was to describe the deaths of fifteen nursing home residents with late-stage dementia. The devastating effect of dementia on a person has been called a ‘living death’ (Woods, 1989). The caring which occurs when someone is going through this process in a nursing home was recorded and analysed. In analysing this act of caring, the second purpose was to look for the origins of the structures and the sources of pressure that shaped the context and therefore helped determine the behaviour of the various groups under observation. These groups were residents and their relatives, the staff of the nursing home and the treating doctors. Before commencing observations and carrying out this study, an understanding needed to be developed of: the condition of dementia as it is perceived by health professionals and presented in the media; the institutions in which the majority of people with dementia end their days; the background and conditions of the staff who nurse in them; the models of care that guide and determine policies; and the conceptions of life and death which underpin relevant laws and moral standpoints. Accordingly, in part 1. chapter 1 the history, causes, pathology and effects of dementing conditions are examined. Relevant medical and lay literature including media influences are examined which pertain to the subject of death and dementia and nursing home care. The history of this institutional care is briefly examined together with the growth of the discipline of gerontological nursing. Chapter 2 discusses some of the effects of this history on present day care and the concept of emotional work being carried out within the present day aged care public policy regulations. The moral arguments surrounding illness and dying in Australian society today are briefly discussed. Chapter 3 describes the conceptual framework for the study, the ethnographic method that has been employed and an outline of critical theory as the basis for analysis. The chapter concludes by recounting the practical steps taken to arrange the field work, secure the consent of participants, record data and gather documents, and outlines the ethical considerations given to the undertaking of the study. Chapter 4 describes the context in which the study took place and the first tentative exploration of the culture from an etic perspective. Part 2 describes the death trajectories observed and raises some questions about alternative strategies that may have been considered within a different paradigm of caring. In chapter 5 the death trajectories of each of the fifteen residents in the study are described, each written with a particular emphasis to illustrate aspects of the culture of care that emerged through thematic analysis. Observations, comments and feelings from staff and family are wound in and around these case studies. Chapter 6 looks more closely at the impact of policy and institutional pressure on the milieu in which these deaths took place. Part 3 draws conclusions from the observations and makes suggestions for emancipatory change as viewed from the author's standpoint of critical ethnographic analysis. In the final chapter an argument is presented for policy change that leads a movement towards palliative care practices for people with late-stage dementia. Approaches to implementation of palliative care will need to take account of any expression by the resident such as an advanced directive, indicating a preferred approach to treatment in the period prior to death; a need for a better understanding of such issues as the significance of body breakdown, the manifestations of pain and electrolyte imbalances; the surrounding ethical complexities and shift in public opinion, and perhaps, most of ail, the culture of the institutions in which this dying will take place. A definition of late-stage dementia which might be used in determining patterns of care is set out. A discussion about changes in practice which relate lo communication with treating doctors, the administering of antibiotics, the relief of pain, the mobilisation of residents and the provision of food and water takes place in light of the evidence found. The discussion of these issues is raised in the form of debate. Each aspect needs more rigorous analysis and information so that evidence-based practice, rather than care which is value-laden and emotional, can be used when treatment decisions are made for people with late-stage dementia.

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The insulin-like growth factor (IGF) system is a key regulator of cell growth, survival and differentiation, and these functions are co-modulated by other growth factors including fibroblast growth factor-2 (FGF-2). To investigate IGF/FGF interactions in neuronal cells, we employed neuroblastoma cells (SK-N-MC). In serum free conditions proliferation of the SK-N-MC cells was promoted by IGF-I (25 ng/ml), but blunted by FGF-2 (50 ng/ml). IGF-I-induced proliferation was abolished in the presence of FGF-2 even when IGF-I was used at 100 ng/ml. In addition to our previously described FGF-2 induced proteolytic cleavage of IGFBP-2, we found that FGF-2 increased IGFBP-6 levels in conditioned medium (CM) without affecting IGFBP-6 mRNA abundance. Modulation of IGFBP-2 and -6 levels were not significant mechanisms involved in the blockade of IGF-I action since the potent IGF-I analogues [QAYL]IGF-I and des(1-3)IGF-I (minimal IGFBP affinity) were unable to overcome FGF-2 inhibition of cell proliferation. FGF-2 treated cells showed morphological differentiation expressing the TUJ1 neuronal marker while cells treated with IGF-I alone showed no morphological change. When IGF-I was combined with FGF-2, however, cell morphology was indistinguishable from that seen with FGF-2 alone. FGF-2 inhibited proliferation and enhanced differentiation was also associated with a 70% increase in cell death. Although IGF-I alone was potently anti-apoptotic (60% decreased), IGF-I was unable to prevent apoptosis when administrated in combination with FGF-2. Gene-array analysis confirmed FGF-2 activation of the intrinsic and extrinsic apoptotic pathways and blockade of IGF anti-apoptotic signaling. FGF-2, directly and indirectly, overcomes the proliferative and anti-apoptotic activity of IGF-I by complex mechanisms, including enhancement of differentiation and apoptotic pathways, and inhibition of IGF-I induced anti-apoptotic signalling. Modulation of IGF binding protein abundance by FGF-2 does not play a significant role in inhibition of IGF-I induced mitogenesis.

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The cellular origin of the acetylcholinesterase (AChE) associated with amyloid plaques in the Alzheimer’s disease (AD) brain is unknown. In this study we report that amyloid β-peptides (Aβ) increased AChE levels in both neuronal and astrocytic primary cultures, supporting the possibility that both neurons and glia may make a direct contribution to the pool of AChE seen around amyloid deposits in the AD brain.

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This essay is concerned with the extent to which the attitudes and ideologies of colonial discourse continue to influence contemporary signifying practices in Australian adolescent historical fiction. Under scrutiny are three novels which take issue with the violent aspects of colonisation when so many members of the Indigenous population either died or were forcibly displaced: Melissa Lucashenko’s Killing Darcy, Gary Crew’s No Such Country and Mark Svendsen’s Poison Under Their Lips. Although these texts share a desire to interrogate monolithic versions of Australia’s history, it is argued that such motivations offer no guarantee that the implied audience is positioned to come to an understanding of perspectives belonging to ex-centric Others.