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Biomedical subjects

W G Sowder

Publications and source records attributed to W G Sowder.

5 recordsLinked to original sources

Nonsteroidal antiinflammatory drug modulation of prosthesis pseudomembrane induced bone resorption.

OBJECTIVE: To study the in vitro effect of therapeutic levels of select nonsteroidal antiinflammatory drugs (NSAID) on prosthesis associated pseudomembrane induced bone resorption and cytokine and prostanoid synthesis using tissue obtained from osteoarthritic patients undergoing revision of cemented implants. METHODS: Pseudomembranes were cultured in the presence and absence of therapeutic levels of select NSAID: Processed conditioned media were evaluated for bone resorbing capacity by assessing murine neonatal limb rudiment release of 45Ca. Interleukin 1 (IL-1) and tumor necrosis factor (TNF) were analyzed by bioassay and prostaglandin E2 (PGE2) by radioimmunoassay. RESULTS: Piroxicam, in contrast to indomethacin and sodium salicylate, significantly decreased membrane associated bone resorption. The NSAID effect correlated more consistently with piroxicam downregulation of TNF synthesis than that of IL-1. Consistent drug associated suppression of PGE2 synthesis did not enable differentiation of NSAID effectiveness in suppressing pseudomembrane induced bone resorption. CONCLUSION: Results provide a rational basis for design of animal models and/or further human studies to test the hypothesis that the prophylactic administration of an NSAID can potentially retard the pseudomembrane effected bone resorptive process associated with aseptic cemented prosthesis failure.

Adult↗

NSAID induction of interleukin 1/catabolin inhibitor production by osteoarthritic synovial tissue.

Select classes of nonsteroidal antiinflammatory drugs (NSAID), independent of their cyclooxygenase suppressing property, may potentially regulate pathophysiologic mechanisms operative in accelerated cartilage catabolism occurring in osteoarthritis (OA). Piroxicam has been shown to downregulate the expression of interleukin 1 (IL-1) associated chondrocyte enzyme inducing activity (catabolin) produced by OA synovium. In situ membrane synthesis of catabolin/IL-1 inhibitors functioning at various levels in thymocyte and catabolin bioassay systems is currently shown. The piroxicam effect appears due to a selective increase in production of a naturally occurring inhibitor(s) and/or induction of new inhibitor formation acting on chondrocytes at a post-IL-1 receptor level.

Anti-Inflammatory Agents, Non-Steroidal↗

Prosthesis-associated pseudomembrane-induced bone resorption.

A pseudomembranous structure invariably develops at the cement-bone interface of implanted prostheses in association with aseptic loosening. The tissue has histological characteristics of a foreign body reaction presumably initiated by repetitive microtrauma-associated release of methacrylate cement and polyethylene wear debris. Explant cultures of pseudomembrane and synovial tissue derived from osteoarthritic patients undergoing revision for cemented hip implant failure have been shown to produce interleukin-1, tumour necrosis factor and prostaglandin E2, recognized mediators of bone resorption. Further, the conditioned media obtained from pseudomembrane cultures could directly effect bone resorption by inducing 45Ca release from prelabelled limb bone rudiments. Results implicate the prosthesis-associated pseudomembrane in the pathogenesis of the bone resorptive process responsible for prosthesis failure.

Adult↗

Polymethylmethacrylate-induced release of bone-resorbing factors.

A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays.

Animals↗