Indications -- Sepsis/Acute Inflammation Message Board

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Biotech / Medical : Indications -- Sepsis/Acute Inflammation

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From: nigel bates	6/11/2006 3:08:37 PM
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Nicotine analogues as potential sepsis therapies - nature.com Importantly, the delayed administration of nicotine 24 hours after the induction of sepsis by caecal ligation and puncture — which is a clinically relevant model of human sepsis caused by polymicrobial infection — reduced circulating levels of HMGB1, attenuated clinical manifestations of sepsis and significantly improved long-term survival. Therefore, the therapeutic window for the treatment of established human disease with nicotine or other more-specific 7nAChR agonists is far greater than that for neutralization of TNF. Furthermore, as this pathway inhibits the release of HMGB1, it is likely to have fewer side effects in clinical trials than antibody-blocking strategies directed at extracellular HMGB1. Finally, the authors suggest that, because a wide variety of cytokines and mediators, not just endotoxin, converge on activation of the NF-B pathway, the nicotinic anti-inflammatory pathway might inhibit HMGB1 release in a range of inflammatory scenarios...

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