Effects of long-term treatment with D-penicillamine on antigen-induced arthritis in rabbits: studies on in vivo articular chondrocyte damage and in vitro collagen biosynthesis by cultured chondrocytes.

The effects of a long-term (120 days) treatment with D-penicillamine (DP) (50 mg/kg/day; i.v.) on antigen-induced arthritis were studied in rabbit. They were investigated by the terminal histological examination of the joints of different groups of rabbits (unimmunized treated or untreated, immunized treated or untreated) and the study of collagen and non-collagen protein biosynthesis by cultured chondrocytes obtained from articular cartilage of the same groups of animals. Treatment with D-penicillamine diminished the intensity of the erosions of cartilage and subchondral bone, the severity of the inflammatory synovitis, and the loss of chondrocyte clusters found in cartilage sections. In cultures of chondrocytes obtained from immunized treated rabbits, a partial or complete inhibition of the decreased biosynthesis of collagen and non-collagen proteins seen in culture of chondrocytes obtained from immunized untreated animals was observed. These results show that DP could be effective in preventing damage of chondrocytes and inhibition of collagen biosynthesis in them, phenomena important in cartilage destruction induced by a chronic immunological inflammation.

Comparison of effects of D. Penicillamine and dexamethasone on the articular and non articular lesions in immune connective tissue disease induced in rabbits.

The effect of D. Penicillamine (DP) at the dose of 50 mg/kg/day, on an immune induced connective tissue disease in rabbit, is compared to that of dexamethasone (Dexa) at the doses of 0.15 and 0.075 mg/kg/day. This model includes polyarthritis and lesions of connective tissue of liver, kidneys and lungs. The result of immunization is initially a non-specific macrophage infiltration and secondarily a specific lymphocyte and plasma-cell infiltration. In short treatment, high dose of Dexa inhibits the non-specific and specific responses while DP modifies only non specific response. In long treatment, Dexa at low dose and DP inhibit the two responses. Data suggest that, in vivo, macrophages is the target cell of DP.

[Hydroxyapatite rheumatism (multiple tendon calcification disease). II. - Microscopic study - HL-A antigen - Experimental arthritis - Pathogeny]. / Le rhumatisme à hydroxyapatite (la maladie des calcifications tendineuses multiples). II - Etude microscopique - Antigène HLA - Arthrite expérimentale - Pathogénie.

Optical and electron microscopic studies of the articular fluid in multiple calcification disease reveals the existence of rounded intra- and extracellular crystalline formations. These crystalline formations of calcium and phosphorus are made up of accumulations of tiny crystals shaped like fine needles 200 nm X 15-20 nm and are highly suggestive of hydroxyapatite. Crystals injected into the plantar pads of rats or the knees of rabbits induce an acute inflammatory reaction maximal at 5 hours and recovering in 24 72 hours. Hydroxyapatite crystals are swiftly dissolved in serum and more rapidly still when cells are present. Their dissolution releases calcium into the surrounding area. HLA typing of patients with multiple tendinous calcification (28 cases) or single tendinous calcification (10 cases) shows an increased frequency of HLA A2 and BW 35 in comparison with controls.