BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is ...BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.展开更多
Terra SAR-X图像的几何校正和辐射定标对于获取地面目标高精度地理位置信息和辐射特征具有重要意义。采用距离-多普勒间接定位模型和仿射校正模型进行SAR影像几何校正,同时完成地形辐射校正并对辐射定标精度进行验证。距离向和方位向上...Terra SAR-X图像的几何校正和辐射定标对于获取地面目标高精度地理位置信息和辐射特征具有重要意义。采用距离-多普勒间接定位模型和仿射校正模型进行SAR影像几何校正,同时完成地形辐射校正并对辐射定标精度进行验证。距离向和方位向上达到了约0.3 m和0.4 m的几何定位精度;相对辐射定标精度优于0.3 d B,绝对辐射定标精度为0.22 d B,所以该模型能达到方法较高的精度且简单快捷。展开更多
基金National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award,No.5R44AI080009.
文摘BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.
文摘Terra SAR-X图像的几何校正和辐射定标对于获取地面目标高精度地理位置信息和辐射特征具有重要意义。采用距离-多普勒间接定位模型和仿射校正模型进行SAR影像几何校正,同时完成地形辐射校正并对辐射定标精度进行验证。距离向和方位向上达到了约0.3 m和0.4 m的几何定位精度;相对辐射定标精度优于0.3 d B,绝对辐射定标精度为0.22 d B,所以该模型能达到方法较高的精度且简单快捷。
