No abstract

were found to be present in the cartilage before induction of a flare up. (Ann Rheum Dis 1999;58:350-356)

We have previously shown that enteral and parenteral supplementation of nucleotides (NT) accelerates healing of small-bowel ulcers in rats with indomethacin-induced ileitis. The purpose of this study was to evaluate whether dietary NT supplementation would similarly affect ulcer healing in dextran sulfate sodium (DSS)-induced colitis in rats. Male Sprague-Dawley rats were randomly assigned to receive either nucleotide-free (NF) or NT-supplemented diets. After 2 d of prefeeding, colitis was induced by including 40 g/L of DSS in drinking water for 3 d, followed thereafter by tap water. Rats from each group were killed at 7 and 12 d after induction of colitis. Additional rats were also used for both the groups as controls (untreated groups). The length of colon was measured and evaluated by histological score. Colonic myeloperoxidase (MPO) activity was assessed. In a separate series of experiments, rats were studied at 0, 4, 7, and 12 d for interleukin-1beta (IL-1beta) in rectal dialysate and plasma. Ulceration predominated in the distal colon in DSS-treated rats. There was no significant difference between the histological scores of the NF and NT-supplemented groups either at 7 or 12 d. MPO activity at 7 and 12 d was significantly higher in the NT-supplemented compared to NF group (7 d: 1013 +/- 172 vs. 409.9 +/- 103.2; 12 d: 471.9 +/- 112.4 vs. 223.6 +/- 21.6 units. min-1. g colon-1). IL-1beta concentration in rectal dialysate was significantly higher at 7 d in both groups compared to 0 and 4 d. At 12 d it continued to be significantly elevated in the NT-supplemented group and was greater than in the NT-free group. Our data on the proinflammatory cytokine, in conjunction with MPO activity, strongly suggest that NT supplementation aggravates the severity of DSS-induced colitis in rats.

No abstract

The reparative responses of articular cartilage after an arthritic insult have not been studied extensively to this day. In the present study, we injected interleukin-1 (IL-1) into knee joints of mice to provoke a mild and transient arthritic insult, and characterized both the catabolic and the subsequent recovery phase. In the catabolic phase, which lasted 2 days after IL-1 injection, proteoglycan (PG) breakdown was profoundly accelerated and PG synthesis was markedly inhibited. Sulfation and polysaccharide synthesis were not affected, yet the number of chondroitin sulfate chains was decreased. The general chondrocyte protein synthesis was not inhibited by IL-1. IL-1 injected every other day for a total of three injections prolonged this catabolic phase and resulted in frank loss of articular cartilage proteoglycans. In the recovery phase, started 3 days after IL-1, PG synthesis was enhanced (1.7 times the normal) and proteoglycans had normal hydrodynamic properties. Remarkably, PG degradation was significantly decreased (approximately 50% of the normal). Zymographic analysis demonstrated enhanced expression of gelatinolytic activities in the extracts of the articular tissues shortly after IL-1 exposure and decreased levels in the recovery phase. We found that the overshoot of PG synthesis and impaired degradation act together to facilitate full cartilage repair 7 days after the last of the three IL-1 injections.