Plos One
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Hemorrhagic shock is a frequent cause of liver failure and often leads to a fatal outcome. Several studies have revealed that p38 MAPK is a key mediator in hemorrhagic damage of the primary organs through the activation of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. However, the precise role of these factors in liver damage following hemorrhagic shock is unclear. ⋯ FR167653 inhibited the inflammation-related hepatic injury following hemorrhagic shock. Bacterial lipopolysaccharide (LPS) derived from the gut appeared to have little effects on the hepatic damage. These results demonstrate that p38 MAPK activation is induced by hepatic ischemia during hemorrhagic shock and plays an important role both in the hepatic expression of proinflammatory cytokines and in the development of inflammation-related liver damage.
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The thalamocortical system plays a key role in the breakdown or emergence of consciousness, providing bottom-up information delivery from sensory afferents and integrating top-down intracortical and thalamocortical reciprocal signaling. A fundamental and so far unanswered question for cognitive neuroscience remains whether the thalamocortical switch for consciousness works in a discontinuous manner or not. To unveil the nature of thalamocortical system phase transition in conjunction with consciousness transition, ketamine/xylazine was administered unobtrusively to ten mice under a forced working test with motion tracker, and field potentials in the sensory and motor-related cortex and thalamic nuclei were concomitantly collected. ⋯ The hyperpolarization curve as a function of anesthetic concentration demonstrated a hysteresis loop, with a significantly higher anesthetic level for transition to the down state compared to transition to the up state. Together, our findings concerning the nature of phase transition in the thalamocortical system during consciousness transition further elucidate the underlying basis for the ambiguous borderlines between conscious and unconscious brains. Moreover, our novel analysis method can be applied to systematic and quantitative handling of subjective concepts in cognitive neuroscience.
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Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2)S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2)S as a non-physiological bolus and thus alternative H(2)S donors are sought. ⋯ Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H(2)S contributes to uterine quiescence from mid-gestation until labor, (ii) that H(2)S affects L-type calcium channels and K(ATP) channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H(2)S plays a physiological role in relaxing myometrium, and thus (iv) H(2)S is an attractive target for therapeutic manipulation of human myometrial contractility.
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Mitochondrial dysfunction is one of the pathogenic mechanisms that lead to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). Astrocytes expressing the ALS-linked SOD1(G93A) mutation display a decreased mitochondrial respiratory capacity associated to phenotypic changes that cause them to induce motor neuron death. Astrocyte-mediated toxicity can be prevented by mitochondria-targeted antioxidants, indicating a critical role of mitochondria in the neurotoxic phenotype. ⋯ A remarkable effect of DCA was the improvement of grip strength performance at the end stage of the disease, which correlated with a recovery of the neuromuscular junction area in extensor digitorum longus muscles. Systemic DCA also decreased astrocyte reactivity and prevented motor neuron loss in SOD1(G93A) mice. Taken together, our results indicate that improvement of the mitochondrial redox status by DCA leads to a disease-modifying effect, further supporting the therapeutic potential of mitochondria-targeted drugs in ALS.
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Review Meta Analysis
Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.
Airway procedures associated with an increased risk of SARS transmission to HCWs include tracheal intubation (OR 6.6), non-invasive ventilation (OR 3.1), tracheotomy (OR 4.2) and manual ventilation (OR 2.8).
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