Biomedical subjects

P Colville-Nash

Publications and source records attributed to P Colville-Nash.

4 recordsLinked to original sources

PubMed1997

The depletion of substance P by diclofenac in the mouse.

Diclofenac in hyaluronan is analgesic and angiostatic. The depletion of substance P may be a common mechanism. Mice received diclofenac, diclofenac in hyaluronan, or saline i.v. for 5 days and snout substance P assessed: saline 2.80 +/- 0.23; 0.5 mg/kg diclofenac 2.03 +/- 0.20 (P < 0.05); diclofenac in hyaluronan 1.88 +/- 0.21 (P < 0.02); capsaicin 1.45 +/- 0.26 fmol/mg tissue (P < 0.005). Substance P recovered by 5 days (diclofenac in hyaluronan, capsaicin) and 24 h (diclofenac). Diclofenac may deplete substance P in analgesia, and hyaluronan prolong the depletion.

Analgesics↗

PubMed1993

Inflammation-induced cartilage degradation in female rodents. Protective role of sex hormones.

OBJECTIVE: To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation. METHODS: We used an in vivo model of inflammation-induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin-1 (IL-1) production by granulomatous tissue, and its effects on female mouse articular cartilage. RESULTS: Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL-1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagonized the effects of IL-1 on both proteoglycan loss and proteoglycan synthesis. CONCLUSION: These data suggest that sex steroids have an important influence on inflammation-induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.

Animals↗

PubMed1989

Cellular interaction in cartilage degradation.

Rat femoral head cartilages (FHCs) in culture for six days retained their glycosaminoglycan (GAG) content and were not affected by recombinant human interleukin-la (IL-1), conditioned media from concanavalin-A stimulation of sensitized lymphocytes (lymphocyte media), or conditioned media from lymphokine-stimulated macrophages (macrophage media). Similarly FHCs cultured with macrophages in the presence of IL-1, lymphocyte medium or macrophage medium did not suffer a loss of GAG. However, FHCs cultured with fibroblasts showed a substantial loss of GAG. This fibroblast-mediated cartilage degradation was significantly increased by IL-1 and macrophage media respectively. Stimulation of fibroblasts by lymphocyte media failed to increase the loss of GAG. It is proposed that cartilage degradation in inflammatory joint disease is brought about by a sequential cell-to-cell interaction via cytokines leading ultimately to stimulation of fibroblast-mediated cartilage degradation.

Animals↗

PubMedDate not supplied

New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression. This mini review concentrates on the formation and maintenance of pannus, the granulomatous tissue responsible for cartilage and bone erosion. This reveals a number of possible therapeutic targets. Protease inhibitors could be used to interfere with the degradatory processes. The diverse functions of endothelial cells suggest oedema formation, cell accumulation and supply of nutrients to the granulomatous tissue could all be targeted by appropriate therapy. Alternatively the immune processes that control pannus formation and state of activation could be regulated by interfering with antigen presentation and the cytokine network.

Anti-Inflammatory Agents, Non-Steroidal↗