Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

10.1371/journal.pntd.0002373PLoS Neglected Tropical Diseases78

P-selectin dependent targeting to inflamed endothelium of recombinant P-selectin glycoprotein ligand-1 immunoglobulin chimera-coated poly[N-(2-hydroxypropyl) methacrylamide]-DNA polyplexes in vivo visualised by intravital microscopy.

BACKGROUND: Developing vectors that target specifically to disease sites after systemic injection is an important goal in gene therapy research. METHODS: We prepared fluorescent DNA polyplexes (< or =150 nm in diameter) comprising plasmid DNA condensed with poly(L-lysine) and coated with a multivalent reactive copolymer based on poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA). These polyplexes were then surface modified with a recombinant P-selectin glycoprotein ligand-1 immunoglobulin chimera (rPSGL-Ig) previously investigated as a selectin antagonist in clinical studies. RESULTS: Five minutes after jugular vein injection of these polyplexes, fluorescence accumulation in inflamed cremasteric venules of C57BL6 mice was more than eight-fold higher than that observed after injection of Fc-blocked control polyplexes. Fluorescence above background was not observed in P-selectin deficient mice, confirming the specificity for P-selectin in this model. CONCLUSIONS: These data provide encouragement for the further development of rPSGL-Ig-coated polyplexes as potential nonviral vectors for targeted gene therapy in inflammatory conditions, such as ischaemia reperfusion injury, unstable atherosclerotic plaques and myocarditis. This approach may also be transferable to the use of other targeting ligands whose cognate partner is specifically upregulated on the vascular endothelium in individual pathological situations

<title language="eng">A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin

<abstract language="eng">The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibt eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo