THR0921, a novel peroxisome proliferator-activated receptor gamma agonist, reduces the severity of collagen-induced arthritis

THR0921 is a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist with potent anti-diabetic properties. Because of the proposed role of PPARγ in inflammation, we investigated the potential of orally active THR0921 to inhibit the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in DBA/1J mice by the injection of bovine type II collagen in complete Freund's adjuvant on days 0 and 21. Mice were treated with THR0921 (50 mg/kg/day) starting on the day of the booster injection and throughout the remaining study period. Both clinical disease activity scores as well as histological scores of joint destruction were significantly reduced in mice treated with THR0921 compared to untreated mice. Proliferation of isolated spleen cells, as well as circulating levels of IgG antibody to type II collagen, was decreased by THR0921. Moreover, spleen cell production of IFN-γ, tumor necrosis factor (TNF)-α and IL-1β in response to exposure to lipopolysaccharide or type II collagen was reduced by in vivo treatment with THR0921. Steady state mRNA levels of TNF-α, IL-1β, monocyte chemotactic protein-1 and receptor activator of nuclear factor κB ligand (RANKL) in isolated joints were all decreased in mice treated with THR0921. Finally, THR0921 inhibited osteoclast differentiation of bone marrow-derived cells stimulated with macrophage colony-stimulating factor and RANKL. In conclusion, THR0921 attenuates collagen-induced arthritis in part by reducing the immune response. As such, PPARγ may be an important therapeutic target for rheumatoid arthritis

Ground state and finite temperature behavior of 1/4-filled band zigzag ladders

We consider the simplest example of lattice frustration in the 1/4-filled band, a one-dimensional chain with next-nearest neighbor interactions. For this zigzag ladder with electron-electron as well as electron-phonon interactions we present numerical results for ground state as well as thermodynamic properties. In this system the ground state bond distortion pattern is independent of electron-electron interaction strength. The spin gap in the ground state of the zigzag ladder increases with the degree of frustration. Unlike in one-dimension, where the spin-gap and charge ordering transitions can be distinct, we show that in the ladder they occur simultaneously. We discuss spin gap and charge ordering transitions in 1/4-filled materials with one, two, or three dimensional crystal structures. We show empirically that regardless of dimensionality the occurrence of simultaneous or distinct charge and magnetic transitions can be correlated with the ground state bond distortion pattern.Comment: 12 pages, 8 eps figure