Journal of internal medicine
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Considerable efforts have been made to understand the role of oxidative stress in age-related diseases and ageing. The mitochondrial free radical theory of ageing, which proposes that damage to mitochondrial DNA (mtDNA) and other macromolecules caused by the production of reactive oxygen species (ROS) during cellular respiration drives ageing, has for a long time been the central hypothesis in the field. However, in contrast with this theory, evidence from an increasing number of experimental studies has suggested that mtDNA mutations may be generated by replication errors rather than by accumulated oxidative damage. ⋯ A number of recent experimental findings strongly question the mitochondrial free radical theory of ageing, leading to the emergence of new theories of how age-associated mitochondrial dysfunction may lead to ageing. These new hypotheses are mainly based on the underlying notion that, despite their deleterious role, ROS are essential signalling molecules that mediate stress responses in general and the stress response to age-dependent damage in particular. This novel view of ROS roles has a clear impact on the interpretation of studies in which antioxidants have been used to treat human age-related diseases commonly linked to oxidative stress.
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Review
Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden.
In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden. ⋯ Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300-400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden.
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Cardiac disease is the most common cause of mortality in Western countries, with most deaths due to out-of-hospital cardiac arrest (OHCA). In Sweden, 5000-10 000 OHCAs occur annually. During the last decade, the time from cardiac arrest to start of cardiopulmonary resuscitation (CPR) and defibrillation has increased, whereas survival has remained unchanged or even increased. ⋯ Postresuscitation, use of therapeutic hypothermia, the importance of specific prognostic survival factors in the intensive care unit and the widespread use of percutaneous coronary intervention have all been considered. Despite progress in research and improved treatment regimens, most patients do not survive OHCA. Particular areas of interest for improving survival include (i) identification of high-risk patients prior to their arrest (e.g. early warning symptoms and genes); (ii) increased use of bystander CPR training (e.g. in schools) and simplified CPR techniques; (iii) better identification of high-incidence sites and better recruitment of AEDs (via mobile phone solutions?); (iv) improved understanding of the use of therapeutic hypothermia; (v) determining which patients should undergo immediate coronary angiography on hospital admission; and (vi) clarifying the importance of extracorporeal membrane oxygenation during CPR.
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Review
Manganese toxicity in the central nervous system: the glutamine/glutamate-γ-aminobutyric acid cycle.
Manganese (Mn) is an essential trace element that is required for maintaining proper function and regulation of numerous biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system (CNS). ⋯ Its toxicity is associated with disruption of the glutamine (Gln)/glutamate (Glu)-γ-aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons, thus leading to changes in Glu-ergic and/or GABAergic transmission and Gln metabolism. Here we discuss the common mechanisms underlying Mn-induced neurotoxicity and their relationship to CNS pathology and GGC impairment.
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Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. ⋯ With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder.