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NAMA : Prof.DR.dr.Harry Isbagio,SpPD K-R,K-GER,FINASIM

TEMPAT/TGL.LAHIR : Magelang, 24 Desember 1948

JABATAN : Guru Besar Divisi Reumatologi Dep. Ilmu Penyakit Dalam FKUI/RSUPN Ciptomangunkusumo Jakarta

PENDIDIKAN : Tamat Dokter 1972 FKUIBrevet Spesialis Penyakit Dalam 1979 FKUIBrevet Subspesialis Reumatologi 1986 FKUIBrevet Subspesialis Geriatri 1996 FKUIDoktor 2004 FKUIGuru Besar 2005 FKUI

ORGANISASI :Ketua Umum, Ikatan Reumatologi Indonesia, 1994 2005President , Rheumatology Association of ASEAN 2001 2006Ketua Bidang Sp Konsultan, Kolegium Ilmu Penyakit Dalam (KIPD), 2006- 2012

The Role Diacerein in the Management of OsteoathrosisHarry Isbagio

Pathogenesis of OA Wear and tear ?It is not necessarily age relatedIt is asymmetrically distribution/ localizedIt is progress steadilyThe sign & symptoms of inflammationRole of inflammation in OA, what is the evidence ?What are inflammatory factors that could possibly be involved in genesis of OA structural changes?Evidence of inflammation in OA

NormalOsteoarthritisEpisodic of acute inflammationSynovial fluid cell count more than normal rangeCellular infiltration in synovial tissueIncrease level of inflammatory mediators in synovial fluid

Osteoarthritis chondrocyteIncrease functionsType II collagen and aggrecan synthesis (early OA)Cell proliferation Catabolic cytokine productionMMPs, TPA/plasminIL-I receptor type 1, NOS/NO, Cox-2/PGE2Apoptosis, Decrease functionsType II collagen and aggrecan synthesis (late OA)IL-1 receptor antagonistResponse to IGF-1Chondrocyte metabolismCatabolismAnabolismChondrocyteStimulationIGFs, TGF-beta, PDGF, EGFBone morphogenic proteinCartilage derived morphogenic proteinGrowth factorStimulationGamma- InterferonTNF-alphaProstaglandinsOxygen radicals, NOIL-1, TNF-alpha, IL-17, FGFs, gamma interferonLeukemia inhibitory factorGlucocorticoidPro-collagen fragmentsInhibitionTIMP, Plasminogen activator inhibitorCalicreinInhibitionChondrocytesPro-MMPsActive-MMPsExtra-cellular matrix degradationCytokinesIL-1, TNF+Growth factorsIGF, TGF-b+PKC, NF-KB, Kinase inhibitorsPA, plasmin++Thiol, serine proteases, MT-MMPs+TIMPs-Heavy metal chelators (Ca, Zn)-Modified from Pelletier JP, Arthritis Rheum 2001;44:1237NONO++++Management of OsteoarthritisNon-pharmacological therapyPharmacological therapySurgery

OA KNEE

Cell membraneIL-1Intracellular signallingCOXNOSPlasminPGsNOActivation of MMPsStromelysinDegrades cartilageCollagenaseDegrades cartilage TGF-B IGF-1 Collagen II Aggrecans Hyaluronic acidMechanism of action of diacereinDiacerein

ConclusionNon-pharmacological therapy is as important as pharmacological therapy, and should be used in all casesThere are some evidences that SYSADOAs, eg. diacerein is effective in osteoarthritis, and when used for a long term period they might be able to modify cartilage structure (disease modifying osteoarthritis drugs: DMOADs).Diacerein is as effective as NSAIDs in osteoarthritis, and is well tolerate. Thank You