Plos One
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Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. ⋯ AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality.
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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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An antianginal K(ATP) channel opener nicorandil has various beneficial effects on cardiovascular systems; however, its effects on pulmonary vasculature under pulmonary arterial hypertension (PAH) have not yet been elucidated. Therefore, we attempted to determine whether nicorandil can attenuate monocrotaline (MCT)-induced PAH in rats. ⋯ Nicorandil attenuated MCT-induced vascular endothelial damage and PAH through production of eNOS and anti-apoptotic factors, suggesting that nicorandil might have a promising therapeutic potential for PAH.
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While there are a variety of identifiable causes of constipation, even idiopathic constipation has different possible mechanisms. Sennosides, the main laxative constituents of Daio, an ancient Kampo medicine, are prodrugs that are converted to an active principle, rheinanthrone, by intestinal microbiota. In this study, we aimed to determine the sennoside hydrolysis ability of lactic acid bacterial strains and bifidobacteria in the intestine and to investigate their effect on intestinal peristalsis in mice. ⋯ We demonstrated that intestinal peristalsis was promoted by rheinanthrone produced by hydrolysis of sennoside by strain LKM512 and LKM10070.
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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.