The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rat

SummaryObjectiveDuring the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigators.MethodsThe experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring. Considerations were made for reproducibility and ease of use for new scorers. Additional scoring paradigms may be employed to further identify specific effects of some disease-modifying drugs.ResultsAlthough the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the reliability study showed that it is easily understood and can be reproducibly used, even by inexperienced scorers.ConclusionsThe scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility. Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models

Far-infrared vibrational properties of high-pressure-high-temperature C60 polymers and the C60 dimer

We report high-resolution far-infrared transmission measurements of the 2 + 2 cycloaddition C-60 dimer and two-dimensional rhombohedral and one-dimensional orthorhombic high-pressure high-temperature C60 polymers. In the spectral region investigated(20-650 cm(-1)), we see no low-energy interball modes, but symmetry breaking of the linked C-60 balls is evident in the complex spectrum of intramolecular modes. Experimental features suggest large splittings or frequency shifts of some IhC60-derived modes that are activated by symmetry reduction, implying that the balls are strongly distorted in these structures. We have calculated the vibrations of all three systems by first-principles quantum molecular dynamics and use them to assign the predominant IhC60 symmetries of observed modes. Pur calculations show unprecedentedly large downshifts of T-1u(2)-derived modes and extremely large splittings of other modes, both of which are consistent with the experimental spectra. For the rhombohedral and orthorhombic polymers, the T-1u(2)-derived mode that is polarized along the bonding direction is calculated to downshift below any T-1u(1)-derived modes. We also identify a previously unassigned feature near 610 cm(-1) in all three systems as a widely split or shifted mode derived from various silent IhC60 vibrations, confirming a strong perturbation model for these linked fullerene structures