17 research outputs found

    Representative photomicrographs of full-thickness inflamed rat colon showing the distribution pattern of collagen fibers stained with van Gieson (VG, A-D), Sirius Red (SR, E-H) or Sirius Red/Fast Green (SR/FG, I-L).

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    <p>CM and LM: circular and longitudinal muscle, respectively; MP: myenteric plexus. Scale bars represent 50╬╝m. Scatter plots show the percentage of positive pixel (PPP) of collagen ┬▒ SEM obtained from 6 rats in the whole colonic wall (M) and <i>tunica muscularis</i> (N). *,┬░ P = 0.028 <i>versus</i> VG and SR, respectively.</p

    Representative photomicrographs of haematoxylin/eosin-stained full-thickness colonic samples from normal rats (A,B), or rats with DNBS-induced colitis at day 6 (C,D).

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    <p>Normal colon displays a normal morphological architecture of the wall and myenteric ganglia. In the inflamed colon, the following alterations are evident: infiltrated <i>tunica submucosa</i>; thickened and infiltrated <i>tunica muscularis</i> and <i>serosa</i>; vacuolated myenteric ganglia with altered cells and abundant eosinophilic infiltrations along the myenteric ridge (D, arrows and arrowheads, respectively). Scale bars represent 50 ╬╝m.</p

    Preparations of longitudinal smooth muscle isolated from normal (A) or DNBS-treated rats (colitis) (B).

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    <p>Effects of increasing concentrations of A804598 (0.001ÔÇô10 ┬ÁM) on contractions evoked by sES (0.5 ms, 10 Hz, 30 mA, 10 s) in preparations maintained in standard Krebs solution. Each column represents the mean┬▒SEM obtained from 6 experiments. *P<0.05, versus control (CON).</p

    Double-staining immunohistochemistry showing the distribution of P2X7 receptors (green) and the neuronal marker HuC/D (red) in the myenteric plexus of colonic cryosections from control (A; normal) or DNBS-treated (B; colitis) rats.

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    <p>Nuclei were stained with TOTO-3. Scale bar: 21 ┬Ám. Enlarged view of HuC/D<sup>+</sup> and P2X7<sup>+</sup> cells in the myenteric ganglia of normal and colitis rats from boxed area in overlay (scale barÔÇŐ=ÔÇŐ10 ┬Ám). LM, longitudinal muscle; CM, circular muscle; MG, myenteric ganglia. Isotype fluorescent image was obtained by labeling with streptavidin conjugated with Alexa Fluor 555 in presence of normal mouse antiserum instead of the primary antibody.</p

    Double immunostaining showing the expression of P2X7 receptors (green) and the glial marker GFAP (red) in myenteric plexus of colonic cryosections from control (A; normal) and DNBS-treated (B; colitis) rats.

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    <p>Nuclei were stained with TOTO-3. Scale bar: 21 ┬Ám. Enlarged view of GFAP<sup>+</sup> and P2X7<sup>+</sup> cells in the myenteric ganglia of normal and colitis rats from boxed area in overlay (scale barÔÇŐ=ÔÇŐ10 ┬Ám). LM, longitudinal muscle; CM, circular muscle; MG, myenteric ganglia. Isotype fluorescent image was obtained by labeling with Alexa Fluor 555 conjugated secondary antibody in presence of normal mouse antiserum instead of the primary antibody.</p

    Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease

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    Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of inflammatory bowel disease. In this work, we report the design, synthesis, and biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of <b>11</b> (INF39), a nontoxic, irreversible NLRP3 inhibitor able to decrease interleukin-1╬▓ release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 activation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration
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