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    Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 by macrophages and increases the resistance of mice against infections

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    Background: Palmitoylethanolamide (PEA), an endogenous lipid and a congener of anandamide, possesses a wide range of effects related to metabolic and cellular homeostasis including anti-inflammatory and neuroprotective properties. Methods: In vitro, we studied the ability of macrophages to phagocytose Escherichia coli K1 after stimulation with increasing doses of PEA. In vivo, wild-type mice were treated with PEA intraperitoneally 12 hours and 30 minutes before infection. Meningoencephalitis or sepsis was induced by intracerebral or intraperitoneal infection with E. coli K1. Results: Stimulation of macrophages with PEA for 30 minutes increased the phagocytosis of E. coli K1 without inducing the release of TNF alpha or CXCL1. Intracellular killing of E. coli K1 was higher in PEA-stimulated than in unstimulated peritoneal macrophages and microglial cells. Pre-treatment with PEA significantly increased survival of mice challenged intracerebrally or intraperitoneally with E. coli K1. This effect was associated with a decreased production of CXCL1, IL-1 beta and IL-6 in homogenates of spleen and cerebellum in mice treated with PEA. Conclusions: Our observations suggest that these protective effects of PEA in mice can increase the resistance to bacterial infections without the hazard of collateral damage by excessive stimulation of phagocytes

    The Effect of High Pressure on the Heck Reaction − A Contribution to a Deeper Understanding of the Mechanism

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    The influence of high pressure on the Heck reactions of iodobenzene with methyl, ethyl and tert-butyl acrylate, and of both 4-nitrophenyl iodide and 4-nitrophenyl triflate with methyl acrylate, has been studied for the first time by quantitative on-line FT-IR spectroscopy. Reaction rates and activation parameters (DeltaH(double dagger), DeltaS(double dagger), DeltaV(double dagger)) were determined at temperatures between 50 and 120 degreesC and pressures up to 3000 bar. A clear influence on the kinetics of the reactions was observed by the nature of the leaving group and by the steric and electronic features of the acrylate. tert-Butyl acrylate, which is more electron-rich than methyl acrylate according to PES measurements, was found to react 1.4-times faster on average than methyl acrylate and, at elevated pressures, triflate turned out to be a better leaving group than iodide. Thus, the observed activation volume for the reaction of iodobenzene with tert-butyl acrylate (DeltaV(double dagger) = -12cm(3) mol(-1)) is more negative than that of the reaction of iodobenzene with ethyl acrylate (DeltaV(double dagger) = -7 cm(3) mol(-1)) or methyl acrylate (DeltaV(double dagger) = -5 cm(3) mol(-1)). For the variation of the leaving group in 4-nitrophenyl iodide and 4-nitrophenyl triflate, the activation volumes for the reaction of each with methyl acrylate are -9 and -37 cm(3) mol(-1), respectively. The results suggest that the rate-determining step of the overall reaction is not the oxidative addition, but is either the alkene coordination or the subsequent carbopalladation. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

    Toll-like receptor stimulation increases phagocytosis of Cryptococcus neoformans by microglial cells

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    Background: Toll-Like receptors (TLRs) belong to the family of pattern-recognition receptors with a crucial function of recognising pathogen-associated molecular patterns (PAMPs). Cryptococcal meningitis is a potentially fatal disease with a high mortality and risk of neurological sequelae. Methods: We studied the ability of microglial cells to increase the phagocytosis of cryptococci after stimulation with agonists of TLR1/2, TLR3, TLR4 and TLR9. Results: Stimulation of murine microglial cells with these TLR agonists for 24 h increased the phagocytosis of encapsulated Cryptococcus neoformans. Stimulation increased the release of TNF-alpha, CXCL1 (KC), IL-6, IL-10 and MIP-2, which indicated the activation of microglial cells. Unstimulated and TLR agonist-stimulated MyD88-deficient cells showed a reduced ability to phagocytose cryptococci compared to their wild-type counterpart. Intracellular killing of cryptococci was also increased in TLR-stimulated cells compared to unstimulated microglial cells. Conclusion: Our observation suggests that stimulation of microglial cells by TLR agonists can increase the resistance of the brain against CNS infections caused by Cryptococcus neoformans. This may be of interest when an immunocompromised patient is unable to eliminate Cryptococcus neoformans despite antifungal therapy.Else Kroner-Fresenius-Stiftung, Bad Homburg v.d.H.; Sparkasse GottingenOpen-Access-Publikationsfonds 201

    Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 and Streptococcus pneumoniae R6 by microglial cells

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    The ability of microglial cells to phagocytose bacteria after stimulation with the endocannabinoid palmitoylethanolamide (PEA) was studied in vitro. PEA increased the phagocytosis of unencapsulated Streptococcus pneumoniae R6 and encapsulated Escherichia coli K1 by murine microglial cells significantly after 30 min of microglial. stimulation. This suggested that stimulation of microglial cells by PEA can increase the resistance of the brain against CNS infections. (C) 2012 Elsevier B.V. All rights reserved.European Community [223111

    FOLLISTATIN DOES NOT INFLUENCE THE COURSE OF ESCHERICHIA COLI K1 SEPSIS IN A MOUSE MODEL

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    Follistatin (FS) is the binding protein of activin A and inhibits its actions. The activin/FS system participates in the fine tuning of the immune response, and concentrations of activin A and FS are elevated in serum of patients with sepsis. Intraperitoneal injection of FS markedly reduced mortality after lipopolysaccharide-induced inflammation in a mouse model. Here, we investigated whether FS also influences the disease course in a mouse model of sepsis induced by intraperitoneal injection of Escherichia coli K1, a gram-negative bacterium frequently causing septic bacterial infections. Intraperitoneal injection of 10 mu g/mL FS 30 min before infection did not influence survival, weight, motor performance, or bacterial titers of the infected mice. Thus, we could not confirm the protective effect of FS observed during lipopolysaccharide-induced inflammation in our mouse model of E. coli sepsis. Although it is a promising therapeutic tool in chronic or acute inflammatory conditions not caused by virulent pathogens, FS does not seem to increase the resistance to bacterial infections

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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