These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacologic cholinesterase inhibition improves survival in experimental sepsis.
    Author: Hofer S, Eisenbach C, Lukic IK, Schneider L, Bode K, Brueckmann M, Mautner S, Wente MN, Encke J, Werner J, Dalpke AH, Stremmel W, Nawroth PP, Martin E, Krammer PH, Bierhaus A, Weigand MA.
    Journal: Crit Care Med; 2008 Feb; 36(2):404-8. PubMed ID: 18091537.
    Abstract:
    OBJECTIVE: Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic anti-inflammatory pathway. Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo. DESIGN: Prospective, randomized laboratory investigation that used an established murine sepsis model. SETTING: Research laboratory in a university hospital. SUBJECTS: Female C57BL/6 mice. INTERVENTIONS: Sepsis in mice was induced by cecal ligation and puncture. Animals were treated immediately with intraperitoneal injections of nicotine (400 microg/kg), physostigmine (80 microg/kg), neostigmine (80 microg/kg), or solvent three times daily for 3 days. MEASUREMENTS AND MAIN RESULTS: Treatment with physostigmine significantly reduced lethality (p < or = .01) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p < or = .05). Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-kappaB (p < or = .05) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (p < or = .001), and pulmonary neutrophil invasion (p < or = .05). Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. CONCLUSIONS: Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use.
    [Abstract] [Full Text] [Related] [New Search]