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Potential Reversibility (potential + reversibility)
Selected AbstractsEarly detection and prevention of delirium in older patients with cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2004K. MILISEN phd, rn 1 Delirium poses a common and multifactorial complication in older patients with cancer. Delirium independently contributes to poorer clinical outcomes and impedes communication between patients with cancer, their family and health care providers. Because of its clinical impact and potential reversibility, efforts for prevention, early recognition or prompt treatment are critical. However, nurses and other health care providers often fail to recognize delirium or misattribute its symptoms to dementia, depression or old age. Yet, failure to determine an individual's risk for delirium can initiate the cascade of negative events causing additional distress for patients, family and health care providers alike. Therefore, parameters for determining an individual's risk for delirium and guidelines for the routine and systematic assessment of cognitive functioning are provided to form a basis for the prompt and accurate diagnosis of delirium. Guidelines for the prevention and treatment of delirium are also discussed. [source] The evolutionary ecology of senescenceFUNCTIONAL ECOLOGY, Issue 3 2008P. Monaghan Summary 1Research on senescence has largely focused on its underlying causes, and is concentrated on humans and relatively few model organisms in laboratory conditions. To understand the evolutionary ecology of senescence, research on a broader taxonomic range is needed, incorporating field, and, where possible, longitudinal studies. 2Senescence is generally considered to involve progressive deterioration in performance, and it is important to distinguish this from other age-related phenotypic changes. We outline and discuss the main explanations of why selection has not eliminated senescence, and summarise the principal mechanisms thought to be involved. 3The main focus of research on senescence is on age-related changes in mortality risk. However, evolutionary biologists focus on fitness, of which survival is only one component. To understand the selective pressures shaping senescence patterns, more attention needs to be devoted to age-related changes in fecundity. 4Both genetic and environmental factors influence the rate of senescence. However, a much clearer distinction needs to be drawn between life span and senescence rate, and between factors that alter the overall risk of death, and factors that alter the rate of senescence. This is particularly important when considering the potential reversibility and plasticity of senescence, and environmental effects, such as circumstances early in life. 5There is a need to reconcile the different approaches to studying senescence, and to integrate theories to explain the evolution of senescence with other evolutionary theories such as sexual and kin selection. [source] BH3-only proteins Bid and BimEL are differentially involved in neuronal dysfunction in mouse models of Huntington's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2007Juan M. García-Martínez Abstract Apoptosis, a cell death mechanism regulated by Bcl-2 family members, has been proposed as one of the mechanisms leading to neuronal loss in Huntington's disease (HD). Here we examined the regulation of Bcl-2 family proteins in three different mouse models of HD with exon 1 mutant huntingtin: the R6/1, the R6/1:BDNF+/,, and the Tet/HD94 in which the huntingtin transgene is controlled by the tetracycline-inducible system. Our results disclosed an increase in the levels of the BH3-only proteins Bid and BimEL in the striatum of HD mouse models that was different depending on the stage of the disease. At 16 weeks of age, Bid was similarly enhanced in the striatum of R6/1 and R6/1:BDNF+/, mice, whereas BimEL protein levels were enhanced only in R6/1:BDNF+/, mice. In contrast, at later stages of the disease, both genotypes displayed increased levels of Bid and BimEL proteins. Furthermore, Bax, Bak, Bad, Bcl-2, and Bcl-xL proteins were not modified in any of the points analyzed. We next explored the potential reversibility of this phenomenon by analyzing conditional Tet/HD94 mice. Constitutive expression of the transgene resulted in increased levels of Bid and BimEL proteins, and only the Bid protein returned to wild-type levels 5 months after mutant huntingtin shutdown. In conclusion, our results show that enhanced Bid protein levels represent an early mechanism linked to the continuous expression of mutant huntingtin that, together with enhanced BimEL, may be a reporter of the progress and severity of neuronal dysfunction. © 2007 Wiley-Liss, Inc. [source] Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH)CLINICAL ENDOCRINOLOGY, Issue 6 2008Ammon Handisurya Summary Objective To evaluate ,-cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Background Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Design and patients Parameters of glucose metabolism have been investigated in subjects with OH (n = 12) and SH (n = 11). Insulin sensitivity has been assessed by the euglycaemic,hyperinsulinaemic clamp technique and ,-cell function by mathematical modelling of data derived from an oral glucose tolerance test. Results Fasting and dynamic glycaemia as assessed by the AUCGlucose remained unaltered following substitution therapy (P > 0·05). Insulin sensitivity significantly improved only in subjects with OH (P < 0·05). Fasting insulin and proinsulin concentrations increased proportionally in both groups (P < 0·05) with the proinsulin : insulin ratio remaining unchanged (P > 0·05). Total insulin secretion was higher in OH before initiation of therapy (P < 0·05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated (P < 0·05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered (P > 0·05). Conclusion In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose-induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic ,-cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity. [source] | |||||||||||||