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Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist
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Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist
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Journal Article
Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist
2004
Overview
We assessed the efficacy of a new adenosine A2A agonist ATL146e, a potent inhibitor of white blood cell chemotaxis, to reduce cartilage damage in the treatment of septic arthrosis. A live septic arthrosis model was created using Staphylococcus aureus in rabbit knees. Animals were divided into five treatment groups: (1) untreated infected control, (2) antibiotics control, and antibiotics plus ATL146e for (3) 24, (4) 48, or (5) 72 h and assessed at 1, 4, and 7 days. Knees in all ATL146e treated animals exhibited no detectable effusion, and histologic examination revealed near normal cartilage and diminished synovial inflammatory response. Synovial WBC counts decreased with the addition of ATL146e when compared to infected and antibiotic controls. Histologic grading of osteochondral specimens demonstrated improved scores for animals treated with ATL146e compared to infected (p < 0.00004) and antibiotics controls (p < 0.05). Analysis of glycosaminoglycan content revealed significantly decreased loss of articular cartilage following infection in the ATL146e groups when compared to infected (p < 0.03) and antibiotics controls (p < 0.05). Addition of an adenosine A2A agonist to antibiotic therapy decreases joint inflammation and articular cartilage destruction without compromising bacterial clearance in rabbit knees following intraarticular bacterial infection. The use of adenosine agonists selective to the A2A receptor to augment conventional treatment of joint sepsis may be chondroprotective and ultimately help prevent arthrosis. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Publisher
Wiley Subscription Services, Inc., A Wiley Company
Subject
/ Adenosine A2 Receptor Antagonists
/ Animals
/ Arthritis, Infectious - drug therapy
/ Arthritis, Infectious - microbiology
/ Arthritis, Infectious - pathology
/ Cartilage, Articular - drug effects
/ Cartilage, Articular - metabolism
/ Cartilage, Articular - pathology
/ Ceftriaxone - therapeutic use
/ Cyclohexanecarboxylic Acids - therapeutic use
/ Dose-Response Relationship, Drug
/ Female
/ Rabbits
/ Septic
/ Staphylococcus aureus - physiology
/ Synovial Membrane - drug effects
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