Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties

SummaryObjectiveWe sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA.MethodsPost-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment. Disease progression was monitored utilizing micro-magnetic resonance imaging (MRI), micro-computed tomography (CT) and histology. Pertinent features such as osteophytes, subchondral sclerosis, joint effusion, bone marrow lesion (BML), cysts, loose bodies and cartilage abnormalities were included in designing a sensitive multi-modality based scoring system, termed the rat arthritis knee scoring system (RAKSS).ResultsOverall, an inter-observer correlation coefficient (ICC) of greater than 0.750 was achieved for each scored feature. None of the treatments prevented cartilage loss, synovitis, joint effusion, or sclerosis. However, celecoxib significantly reduced osteophyte development compared to placebo. Although signs of inflammation such as synovitis and joint effusion were readily identified at 4 weeks post-operation, we did not detect any BML.ConclusionWe report the development of a sensitive and reliable multi-modality scoring system, the RAKSS, for evaluation of OA severity in pre-clinical animal models. Using this scoring system, we found that celecoxib prevented enlargement of osteophytes in this animal model of PTOA, and thus it may be useful in preventing OA progression. However, it did not show any chondroprotective effect using the recommended dose. In contrast, high dose glucosamine had no measurable effects

Synthesis of pseudopolyrotaxanes-coated Superparamagnetic Iron Oxide Nanoparticles as new MRI contrast agent

Item does not contain fulltextSuperparamagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized and coated with pseudopolyrotaxanes (PPRs) and proposed as a novel hybrid nanostructure for medical imaging and drug delivery. PPRs were prepared by addition of alpha-cyclodextrin rings to functionalized polyethylene glycol (PEG) chain with hydrophobic triazine end-groups. Non-covalent interactions between SPIONs and PPRs led to the assembly of SPIONs@PRs hybrid nanomaterials. Measurements of the (1)H Nuclear Magnetic Resonance (NMR) relaxation times T(1) and T(2) allowed us to determine the NMR dispersion profiles. Comparison between our SPIONs@PRs hybrid nano-compound and the commercial SPION compound, Endorem(R), showed a higher transverse relaxivity for SPIONs@PRs. In vitro MRI experiments showed that our SPIONs@PRs produces better negative contrast compared to Endorem(R) and can be considered as a novel MRI contrast agent