Biomedical subjects

A M Appel

Publications and source records attributed to A M Appel.

7 recordsLinked to original sources

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

In vitro effect of select nonsteroidal antiinflammatory drugs on the synthesis and activity of anabolic regulatory factors produced by osteoarthritic and rheumatoid synovial tissue.

Nutriment replenished conditioned media derived from cultures of osteoarthritic and rheumatoid synovial tissue contain factors of variable molecular weight, independent of prostaglandin activity, which are capable of reversibly down-regulating cartilage matrix proteoglycan synthesis. Piroxicam significantly reduced anabolic suppressant factor production on an apparent selective basis. It could be shown to partially modify the chromatographic profile of newly synthesized osteoarthritic synovial tissue protein fractions containing suppressant activity. Dependent on experimental design, piroxicam also partially blocked inhibitory activity at a chondrocyte level. Indomethacin and sodium salicylate were essentially without effect.

Animals↗

PubMed1988

Modulation of cartilage proteoglycan synthesis by osteoarthritic synovium.

Conditioned media derived from explant cultures of human osteoarthritic synovial tissue have been shown to contain preformed and newly synthesized factors of variable molecular weight which are capable on a concentration dependent basis of modulating cartilage proteoglycan metabolism. Anabolic inhibitory and stimulatory activity often appeared to coexist, a reversible down-regulation usually dominating in unfractionated preparations. The size of newly synthesized proteoglycan aggregates and monomers and the length of glycosaminoglycan chains produced in the presence of conditioned media were normal. The pattern of anabolic response did not necessarily correlate with the presence of catabolic inducing activity.

Cartilage, Articular↗

PubMed1987

Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs. In vitro effect on the synthesis and activity of catabolism-inducing cytokines produced by osteoarthritic and rheumatoid synovial tissue.

Non-enzymatic factors produced by synovial tissue can potentially mediate cartilage destruction by inducing the synthesis and release of matrix-degrading proteinases from chondrocytes. Pharmacologic control of this process is of potential clinical relevance. The in vitro effect of therapeutic concentrations of select nonsteroidal antiinflammatory drugs on the synthesis and activity of catabolism-inducing cytokines produced by 6-day explant cultures of osteoarthritic and rheumatoid synovial tissue was studied. Piroxicam regularly suppressed such factor synthesis by both types of tissue without significantly affecting total protein synthesis. This did not occur using sodium salicylate or indomethacin in osteoarthritis tissue cultures and was observed only occasionally in rheumatoid arthritis cultures. None of the nonsteroidal antiinflammatory drugs studied consistently blocked catabolism-inducing activity in osteoarthritis tissue, whereas piroxicam more consistently inhibited activity produced by rheumatoid arthritis tissue. Results suggest that the catabolism-inducing factors produced by the 2 tissue sources may differ.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1987

Immunologic modulation of cartilage metabolism.

Preservation of the structural integrity of cartilage requires that metabolic homeostasis be maintained between chondrocyte anabolic and catabolic functions. This critical balance is perturbed in osteoarthritis (OA) in which synovial tissue and subchondral intratrabecular marrow often contain a focal and at times more diffuse mononuclear cell infiltration. Cytokines derived from T lymphocytes and monocytes have a capacity to: a) cause qualitative changes in and reversibly suppress chondrocyte proteoglycan, collagen, and non-collagen protein synthesis, and b) induce the synthesis and release of chondrocyte proteinases. Factors having comparable metabolic regulatory activity are produced by synovial tissue derived from idiopathic and secondary forms of OA.

Biological Products↗

PubMed1986

The in vitro effect of select classes of nonsteroidal antiinflammatory drugs on normal cartilage metabolism.

The in vitro effect of piroxicam, a newer nonsteroidal antiinflammatory drug (NSAID), on normal cartilage metabolism has been studied and response contrasted to indomethacin and sodium salicylate. Therapeutic levels of piroxicam has no effect on cartilage glycosaminoglycan (GAG), collagen or noncollagen protein synthesis by porcine weight bearing articular cartilage explants. Salicylate consistently suppressed GAG and protein synthesis, whereas indomethacin had no consistent effect on GAG production but suppressed protein synthesis. NSAID studied had no effect on proteoglycan catabolism. The potential significance of the effect of NSAID on cartilage metabolism is discussed and placed in perspective as regards selection of these agents for human use.

Animals↗