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Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis.

Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Research Abstract Details 

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  • Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Abstract Text:

     ,montserrat aceitunoMontserrat Aceituno, gil Gil,rosa miquelRosa Miquel,josep m Josep M ,azucena salasAzucena Salas,peter mcleanPeter McLean, ,montserrat aceitunoMontserrat Aceituno, gil Gil,rosa miquelRosa Miquel,josep m Josep M ,azucena salasAzucena Salas,peter mcleanPeter McLean,

    Modulation of adhesion molecule expression or function is regarded as a promising therapy for inflammatory conditions. This study evaluates the effects of an inhibitor of adhesion molecule expression (GI270384X) in two experimental models of colitis. Colitis of different severity was induced in C57BL/6J mice by administering 1, 2, or 3% dextran sulfate sodium (DSS). GI270384X (3, 10, or 25 mg.kg(-1).day(-1)) was administered as pretreatment or started 3 days after colitis induction. In IL-10-deficient mice, the highest dose was given for 2 wk. The clinical course of colitis, pathological changes, serum inflammatory biomarkers, expression of adhesion molecules, and leukocyte-endothelial cell interactions in colonic venules were measured in mice treated with vehicle or with active drug. In the most severe forms of colitis (2% and 3% DSS and IL-10-deficient mice), the magnitude of colonic inflammation was not modified by treatment with GI270384X. In a less severe form of colitis (1% DSS), GI270384X treatment dose dependently ameliorated the clinical signs of colitis, colonic pathological changes, and serum levels of biomarkers (IL-6 and serum amyloid A). Administration of 25 mg.kg(-1).day(-1) GI270384X abrogated upregulation of ICAM-1 in the inflamed colon but had no effect on VCAM-1 or E-selectin expression. This was associated with a significant reduction in number of rolling and firmly adherent leukocytes in colonic venules. These results indicate that GI270384X is effective in the treatment of experimental colitis of moderate severity. Reduced adhesion molecule expression and leukocyte recruitment to the inflamed intestine contribute to this beneficial effect.

    Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Publishing Authors By Initials

    j J ,m aceitunoM Aceituno,f gilF Gil,r miquelR Miquel,jm JM ,a salasA Salas,p mcleanP McLean,j J ,m aceitunoM Aceituno,f gilF Gil,r miquelR Miquel,jm JM ,a salasA Salas,p mcleanP McLean,

    For similar membrane glycoproteins: cell adhesion molecules: vascular cell adhesion molecule-1 research abstracts see: membrane glycoproteins: cell adhesion molecules: vascular cell adhesion molecule-1 research

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    Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: American journal of physiology. Gastrointestinal a

    VOLUME: 293

    Page Numbers: G739-48

    Journal Abbreviation: Am. J. Physiol. Gastrointest.

    ISSN: 0193-1857

    DAY: 26

    MONTH: 07

    YEAR: 2007

    Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 100901227

    Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Keywords Mesh Terms:

    KEYWORDS: Vascular Cell Adhesion Molecule-1

    MESH TERMS: biosynthesis

    Chemical & Substance for Abstract: Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis. Information

    Substance Name: Dextran Sulfate

    Registry Number: 9042-14-2

    Grant and Affiliation Information for Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis.

    AFFILIATION: Dept. of Gastroenterology, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. panes@ub.edu

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Am J Physiol Gastrointest Live

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