Effects of Sandimmune neoral on collagen-induced arthritis in DA rats: characterization by high resolution three-dimensional magnetic resonance imaging and by histology.
In the present work the time course of collagen-induced arthritis and the effect of Sandimmune Neoral in this model of arthritis were followed in the rat over an extended period of time (70 days) using high resolution three-dimensional (3D) magnetic resonance imaging (MRI). High resolution 3D gradient-echo (TR = 100 ms; TE = 3.8 ms) images with a voxel size of 94 x 81 x 60 micron3 were acquired from the hind paw of DA rats (n = 21) at various time points after injection of type II bovine collagen into the tail. Eleven rats were treated with Neoral (15 mg/kg/day p.o. together with vehicle) for 42 days starting at day 14 after collagen injection. The remaining controls received vehicle. Pathomorphological changes associated with the collagen-induced arthritic process, e.g., increase of joint space and cartilage and bone erosion, could be observed in vivo in the control group. In contrast, no changes in the joint architecture were detected in Neoral-treated animals. Indeed, Neoral showed strong anti-inflammatory effects and marked protection against cartilage and bone destruction in this model. Qualitative information derived from the MR images correlated significantly with histological findings.
Beckmann
N
N
Core Technologies, Novartis Pharma Inc., Basel, CH-4002, Switzerland.
Bruttel
K
K
Schuurman
H
H
Mir
A
A
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D002417:Cattle; D003094:Collagen / Q000008:administration & dosage / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb; D007114:Immunization; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007271:Injections, Intradermal; D007596:Joints / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008682:Metatarsal Bones / Q000473:pathology; D014677:Pharmaceutical Vehicles; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014677:Pharmaceutical Vehicles; D016572:Cyclosporine; D003094:Collagen