Articles: function.
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With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. ⋯ We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.
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Anesthesia and analgesia · Aug 2016
Comparative StudyThe Biomechanical Effects of Resuscitation Colloids on the Compromised Lung Endothelial Glycocalyx.
The endothelial glycocalyx is an important component of the vascular permeability barrier, forming a scaffold that allows serum proteins to create a gel-like layer on the endothelial surface and transmitting mechanosensing and mechanotransduction information that influences permeability. During acute inflammation, the glycocalyx is degraded, changing how it interacts with serum proteins and colloids used during resuscitation and altering its barrier properties and biomechanical characteristics. We quantified changes in the biomechanical properties of lung endothelial glycocalyx during control conditions and after degradation by hyaluronidase using biophysical techniques that can probe mechanics at (1) the aqueous/glycocalyx interface and (2) inside the glycocalyx. Our goal was to discern the location-specific effects of albumin and hydroxyethyl starch (HES) on glycocalyx function. ⋯ Albumin and HES induced markedly different effects on glycocalyx mechanics and had notably different effects after glycocalyx degradation by hyaluronidase. We conclude that HES is not comparable with albumin for studies of vascular permeability and glycocalyx-dependent signaling. Characterizing the molecular and biomechanical effects of resuscitation colloids on the glycocalyx should clarify their indicated uses and permit a better understanding of how HES and albumin affect vascular function.
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Critical care medicine · Aug 2016
Short-Term Organ Dysfunction Is Associated With Long-Term (10-Yr) Mortality of Septic Shock.
As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock. ⋯ Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
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Journal of critical care · Aug 2016
EditorialNeuroscience and awareness in the dying human brain: Implications for organ donation practices.
Consciousness has 2 components: wakefulness (arousal) and awareness (perception of the self and the external environment). Functional neuroimaging has identified 2 distinctive functional networks that mediate external awareness of the surrounding environment and internal awareness of the self. Recent studies suggest that awareness is not always associated with wakefulness. ⋯ This aligns with the 5-minute no-touch time after the loss of arterial pulse, the current circulatory standard of death determination in non-heart-beating organ donation. We argue that the capacity for awareness may not be irreversibly lost after a relatively brief period of cessation of systemic circulation, and outline empirical data in support of the claim that awareness without wakefulness may be present. Obviously, if correct, this will have practical and ethical implications on organ donation practices.
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Critical care medicine · Aug 2016
Sirtuin 1 Stimulation Attenuates Ischemic Liver Injury and Enhances Mitochondrial Recovery and Autophagy.
Hepatic ischemia-reperfusion is a major clinical problem with limited treatment options. The pathophysiology of hepatic ischemia-reperfusion is characterized by mitochondrial dysfunction and cellular energy deficits. Sirtuin 1 is an energy-sensing enzyme known to modulate mitochondrial biogenesis. We hypothesized that pharmacologic activation of sirtuin 1 is protective after hepatic ischemia-reperfusion injury. ⋯ Pharmacologic stimulation of sirtuin 1 attenuates liver injury after hepatic ischemia-reperfusion by restoring mitochondrial mass and membrane potential, which is associated with the enhancement of autophagy.