Plos One
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Tetrodotoxin-resistant (TTX-R) sodium channels Na(V)1.8 and Na(V)1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported Na(V)1.8, roles of Na(V)1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting Na(V)1.8 and Na(V)1.9 on inflammatory pain. ⋯ Intrathecal (i.t.) delivery of AS ODN was used to down-regulate Na(V)1.8 or Na(V)1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only Na(V)1.8 AS ODN, but not Na(V)1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels Na(V)1.8 and Na(V)1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain.
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Xenon pretreatment may prevent early memory decline after isoflurane anesthesia and surgery in mice.
Postoperative cognitive decline (POCD) is a common complication following surgery, but its aetiology remains unclear. We hypothesized that xenon pretreatment prevents POCD by suppressing the systemic inflammatory response or through an associated protective signaling pathway involving heat shock protein 72 (Hsp72) and PI3-kinase. Twenty-four hours after establishing long-term memory using fear conditioning training, C57BL/6 adult male mice (n = 12/group) received one of the following treatments: 1) no treatment group (control); 2) 1.8% isoflurane anesthesia; 3) 70% xenon anesthesia; 4) 1.8% isoflurane anesthesia with surgery of the right hind leg tibia that was pinned and fractured; or 5) pretreatment with 70% xenon for 20 minutes followed immediately by 1.8% isoflurane anesthesia with the surgery described above. ⋯ Xenon pretreatment also reduced the plasma level increase of IL-1β induced by surgery (P = 0.028). Our data indicated that surgery and/or Isoflurane induced memory deficit was attenuated by xenon pretreatment. This was associated with a reduction in the plasma level of IL-1β and an upregulation of Hsp72 in the hippocampus.
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Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. ⋯ Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation.
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Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. ⋯ Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury.
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The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. ⋯ In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.