No abstract

We examined the osteogenesis process in transforming growth factor beta 1 (TGF-beta 1)-treated neonatal and adult rats, aiming to investigate the age difference in the effect of TGF-beta 1 on mesenchymal cell differentiation. Recombinant human (rh) TGF-beta 1 (20 and 200 ng) was injected onto the outer periostea of the right side of the parietal bone of each rat once a day for 1-12 days starting at the age of either 1 day or 12 weeks. On the day after the final injection, the calvaria was excised and evaluated histologically. In the neonates, the 12-day treatment with rhTGF-beta 1 increased the number of osteoprogenitor cells, resulting in intramembranous ossification. In the adult rats, rhTGF-beta 1 induced differentiation of chondrocytes. Cartilage masses were surrounded by mesenchymal cells, which would differentiate into chondrocytes. The cartilage matrix was partially calcified, with chondrocytes buried therein. In the calcified matrix, marrow cavities containing some multinuclear osteoclasts were formed. These findings indicate that rhTGF-beta 1 stimulated the differentiation of mesenchymal cells into chondrocytes and produced the cartilaginous matrix. rhTGF-beta 1 induced intramembranous ossification of the parietal bone in neonatal rats, and it induced enchondral ossification in adults. This result suggests that the different responses of mesenchymal cells in the periosteum to rhTGF-beta 1 may depend on the age of the animals used: namely, they may reflect the respective osteogenic stages of modeling and remodeling.

No abstract

Leflunomide (HWA 486, a novel isoxazol derivative), shown to have potent immunosuppressant and antiinflammatory effects, was evaluated for its inhibitory and therapeutic effects on the glomerulonephritis induced in rats by rabbit antiserum against rat glomerular basement membrane. Leflunomide was administered orally to rats at 0.5 and 2 mg/kg/day for 20 days from 2 days before injection of the rabbit antiserum and at 2 mg/kg/day for 14 days from 5 days after the antibody injection. The present study consisting of 2 experiments for inhibitory (I) and therapeutic (II) effects of leflunomide revealed the following effects at 2 mg/kg: in experiment I, significant decreases in (a) urinary total protein, (b) plasma total cholesterol and fibrinogen and (c) thymus weight, and decreased incidences of fibrin deposits in Bowman's space, adhesion of the glomerulus to Bowman's capsule and deposition of rat IgG and C3; and in experiment II, decreases in (a), (b) and (c), though smaller than in experiment I, and decreases deposition of rat C3. Thus, leflunomide had potent inhibitory and limited therapeutic effects on glomerulonephritis, suggesting that the compound is effective in inhibiting the onset and development of glomerulonephritis.

No abstract