膝关节骨性关节炎-中英文合并版.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,New Tools for Identifying Inflammatory andOsteoarthritis Phenotypes,Virginia Byers Kraus,MD,PhD,Professor of Medicine,医学教授,Duke University School of Medicine,Duke Institute for Molecular Physiology,Durham,NC,September 2013,识别炎症与骨关节炎表型的新工具,History of Osteoarthritis,From the times of Hippocrates all forms of chronic arthritis were regarded as manifestations of,gout,.(Dequeker and Luyten,2008;,Ann Rheum Dis,67,:5-10).,Sir Archibald Garrod coined the term,osteoarthritis,(OA)in 1890.Debate has raged ever sinceis OA a,mechanical,(,non-inflammatory,)or an,inflammatory,disease?,1890,年，,Archibald Garrod,爵士提出了,”,骨关节,(Osteoarthritis),”(OA),这个名词,.,争论一直持续至今,OA,究竟是一种机械性,(,非炎症,),或是一种,炎症性,疾病？,骨关节炎的历史,从希波克拉底时期，所有形式的慢性关节炎都被认为是,痛风,的表现,History of Osteoarthritis,骨关节炎的历史,Osteoarthritis is BOTH a,mechanical,and an,inflammatory,disease.,骨关节炎既是一种,机械性,疾病也是一种,炎症性,疾病,Signs of Inflammation in Osteoarthritis,are Frequent When Sensitive Tools are Used,Frequent,effusions,频繁,关节积液,Song,2008:78%by ultrasound and 81%by MRI,in,超声检测,78%,和,MRI,检测,81%,Tarhan,2003:70%by ultrasound,80%by,MRI,超声检测,70%,和,MRI,检测,80%,Frequent,synovial,thickening,频繁,滑膜增厚,Tarhan 2003:34,%by ultrasound,50%by,MRI,超声检测,34%,和,MRI,检测,50%,Frequent,popliteal(Bakers)cysts,频繁,腘窝囊肿（,Baker,囊肿）,Tarhan 2003:40%by ultrasound,35%by MRI,超声检测,40%,和,MRI,检测,35%,References,参考文献,:,Song et al.Ann Rheum Dis 2008;67(1):19-25,Tarhan et al.Clin Rheumatol 2003;22(3):181-8,当使用一些敏感的检测手段时,骨关节炎的炎症指标就会频繁出现,Signs of Inflammation in Osteoarthritis,are also Frequent at a Molecular Level,Innate immunity is triggered,先天免疫被激活,High expression and activation of,Complement,补体,激活及高表达,Activation,by,Crystals,:,Calcium pyrophosphate dihydrate,basic calcium phosphate and uric acid,crystals,被,晶体,激活：二水焦磷酸钙化合物,碱性磷酸钙和尿酸结晶,Levels,of several,I,nflammatory Mediators,are higher in OA than healthy,sera and synovial fluid,OA,患者血清及滑夜中一些,炎症介质,的水平高于正常人,Presence of,M,acrophages,in synovium,滑膜中存在,巨噬细胞,References,参考文献,:,Berenbaum F.Osteoarthritis Cartilage 2013;21(1):16-21,Denoble,Kraus et al.Proc Natl Acad Sci U S A 2011;108(5):2088-93,在分子水平上，骨关节炎的炎症指标同样也会频繁出现,Signs of Inflammation in Osteoarthritis can be Demonstrated,in vivo,by 99mTc-EC20 FolateScans,在分子水平上，骨关节炎的炎症指标同样也会频繁出现,The,Folate Receptor is,expressed on,activated,but not resting,macrophages,(Low PS,et al.Acc Chem Res 2008;41(1):120-9,).,活化,非静息的,巨噬细胞,能够表达叶酸受体,A new imaging agent-,99m,Tc,-EC20(Etarfolatide,),can identify activated macrophages,in vivo.,一个新型成像试剂,-,99m,Tc-EC20(Etarfolatide),能够识别体内活化的巨噬细胞,99m,Tc-EC20,(Etarfolatide,)consists,of the vitamin folate,conjugated,to,99m,Tc via a chelating moiety.,一个新型成像试剂,-,99m,Tc-EC20(Etarfolatide),能够识别体内活化的巨噬细胞,Tc,O,99m,Nuclear medicine,radiopharmaceutical,for IV injection,Results SPECT-CT,99m,Tc-EC20,Identifies Activated Macrophages in OA Joints,结果,SPECT（单光子发射CT）-CT,99m,Tc-EC20,识别,OA,关节内活化的巨噬细胞,Subchondral Bone,软骨下骨,Synovial and Joint Space,滑膜与关节腔,Synovial,99m,Tc-EC20 Intensity Associated with Knee Symptoms,滑膜,99m,Tc-EC20,强度与膝关节的症状相关,KNEES 1-50(ordered by synovial,99m,Tc-EC20 uptake),Z SCORE,Z,评分,膝关节,1-50(,按滑膜,99m,Tc-EC20,摄取量排序,),Understanding Osteoarthritis Phenotypes,Kraus inspired by Berenbaum 2013,INNATE IMMUNITY&MACROPHAGES,先天免疫巨噬细胞,对骨关节炎表型的理解,Acknowledgments,致谢,Co-investigators,共同研究者,:,Gary McDaniel,Janet L Huebner,Thomas Stabler,Carl Pieper,R Edward Coleman,Neil A Petry,Philip S Low,Jaiyin Shen,and Peter Mitchell,Hikmat Daghestani,Funding,基金赞助,:,Investigator Initiated Study sponsored in part by:,Lilly,USA,LLC,NIH/NIA,:Claude D Pepper OAIC P30 AG028716,NIH/NIAMS,P01 AR050245,Etarfolatide(EC20)was kindly donated by,Endocyte,(West Lafayette,IN),Thank You,谢谢,