Biomedical subjects

S M Moe

Publications and source records attributed to S M Moe.

23 records · Page 2Linked to original sources

PubMed1992

Beta 2-microglobulin induces calcium efflux from cultured neonatal mouse calvariae.

beta 2-Microglobulin (beta 2M) polymerizes to form amyloid fibrils that deposit and cause destructive bone lesions in patients on chronic dialytic therapy. beta 2 M is mitogenic to osteoblasts; however, its effect on bone mineralization is unknown. To determine whether beta 2M causes bone demineralization, neonatal mouse calvariae were incubated with and without beta 2M, and net calcium flux was calculated. Following a 48-h but not 3- or 24-h incubation, beta 2M (10(-8)-10(-6) M) induced a net calcium efflux. The efflux was similar to that observed with 10(-10) M parathyroid hormone (PTH) but less than that observed with 10(-8 M PTH. Devitalizing the calvariae resulted in a net calcium influx that was unaffected by the addition of beta 2M, indicating a cell-mediated phenomenon. The release of beta-glucuronidase, an osteoclast enzyme, increased after a 48-h but not a 24-h incubation with beta 2M. Calcitonin, an osteoclast inhibitor, blocked the beta 2M-induced calcium efflux and beta-glucuronidase release, suggesting osteoclast involvement. Thus beta 2M induces a dose- and time-dependent, cell-mediated calcium efflux from neonatal mouse calvariae that involves osteoclast stimulation.

Acid Phosphatase↗

PubMedDate not supplied

A coculture model of synoviocytes and bone for the evaluation of potential arthritis therapies.

OBJECTIVE: To evaluate the symbiotic relationship between musculoskeletal cells in the intact joint utilizing a coculture system and to determine if the model can be utilized to evaluate potential treatments for articular diseases. METHODS: Two neonatal mouse calvariae were placed on steel supports on a monolayer of rabbit synovial fibroblasts, and net calcium flux, bone cell activity, and undecalcified histology were determined at 6, 24, and 48 h. To determine if the model was predictive of response to known therapies for articular disease, the coculture was incubated in the presence and absence of indomethacin or doxycycline, and the net calcium flux was measured. RESULTS: The coincubation of calvariae with synoviocytes led to a fivefold increase in net calcium efflux compared to calvariae alone. The concentration in the media of the osteoblastic enzyme alkaline phosphatase increased at 6 h but decreased thereafter, whereas the concentration of osteoclastic enzyme beta-glucuronidase increased with time. Undecalcified bone histology revealed progressive demineralization and an increase in the number of osteoclasts in calvariae incubated with synoviocytes compared to calvariae alone. Both indomethacin and doxycycline inhibited calcium flux from cocultures but the predominant effect of doxycycline was on the synoviocyte whereas the predominant effect of indomethacin was on bone. CONCLUSION: The coincubation of synoviocytes with calvariae led to an increase in bone mineral dissolution with time. This effect could be partially inhibited by known treatments for rheumatoid arthritis. Thus, the coculture model may simulate certain aspects of the in vivo processes relevant to rheumatoid arthritis. This model should prove useful for the study of potential therapies for inflammatory arthritis and distinguish between effects of these therapies on different cellular components of the joint.

Alkaline Phosphatase↗

PubMedDate not supplied

Effect of hemodialysis membranes on beta 2-microglobulin amyloidosis.

Early after the identification of beta(2)-microglobulin amyloidosis (A beta(2)M) as the cause of carpal tunnel syndrome, it was thought that hemodialysis was a major cause in the development of the disease. It was subsequently shown that hemodialysis was not necessary for the development of dialysis-related amyloidosis; however, it was believed that the different dialysis membranes did modulate the progression of the disease. Current data demonstrate that hemodialysis fails to prevent or reverse the disease, but there is substantial evidence that high-flux, high-efficiency dialyzers slow its progression. Many factors related to hemodialysis have been evaluated in relation to A beta(2)M, including the effect of the bioincompatibility of the membrane, the capacity of the different membranes to remove beta(2)M, and the effect of reuse on beta(2)M levels. Moreover, there have been intensive efforts to evaluate, explore, and improve the different mechanisms in beta(2)M removal, with adsorption as a promising prospect. With the available evidence, it seems that the removal of beta(2)M by the membrane plays the most important role in modulating the disease outcome and rate of progression, although a large, long-term, multicentered and randomized study is still lacking to prove this relationship. However, it is possible that with the continuing advances in optimizing the beta(2)M removal efficiency of the different membranes, the frequency and severity of the disease can be substantially decreased.

Amyloidosis↗

PubMedDate not supplied

The role of the synovium and cartilage in the pathogenesis of beta(2)-microglobulin amyloidosis.

The predilection for beta(2)-microglobulin (beta(2)M) amyloid deposition in articular structures is unique compared to other forms of amyloid; this article focuses on possible pathogenic mechanisms. The synovium and/or cartilage appear to be important in the pathogenesis of beta(2)M amyloidosis (A beta(2)M), as amyloid is not found in the shafts of long bones. The concentration of beta(2)M in the joint fluid parallels that in serum. Once in the joint space, evidence suggests that the beta(2)M binds to collagen in cartilage as the initial site of deposition. This binding may serve as the first step in subsequent amyloid formation, although this remains to be proven. beta(2)M has been shown to have many direct effects on synovial fibroblasts, including induction of the release of cytokines, metalloproteinases, cyclooxygenase-2, and vascular cell adhesion molecule-1 (VCAM-1). The release of these inflammatory mediators that lead to tissue degradation is also observed in other forms of arthritis. Thus beta(2)M itself may elicit the release of inflammatory mediators from synovial fibroblasts even in the absence of cellular infiltrates.

Amyloidosis↗

PubMedDate not supplied

Small and middle molecular weight solute clearance in nocturnal intermittent peritoneal dialysis.

OBJECTIVES: To determine the dialysate-to-plasma (D/P) concentration ratios and peritoneal dialytic clearance (CI(D)) of substances with a wide range of molecular weights in subjects receiving a simulated nocturnal intermittent peritoneal dialysis (NIPD) session. DESIGN: Open-label single-dose study. SUBJECTS: Six end-stage renal disease patients undergoing peritoneal dialysis (PD). SETTING: Clinical research center of a university-affiliated hospital. INTERVENTIONS: Subjects received intravenous gentamicin and vancomycin on the first day of the study. Subjects received no PD until their return on the following day, when subjects underwent a simulated NIPD session utilizing four 2- to 2.5-L peritoneal dialysate dwells of 2 hours. Blood and dialysate samples were collected immediately before the session and after each dialysate dwell for determination of urea, creatinine, gentamicin, vancomycin, and beta2-microglobulin (beta2M) concentrations. Each solute's D/P concentration ratio and peritoneal CI(D) were calculated. MEASUREMENTS AND MAIN RESULTS: The (mean +/- SD) 2-hour D/P concentration ratios were 0.78 +/- 0.05 (urea), 0.49 +/- 0.11 (creatinine), 0.38 +/- 0.08 (gentamicin), 0.11 +/- 0.06 (vancomycin), and 0.07 +/- 0.03 (beta2M). Peritoneal CI(D) values (mL/min of dialysis) were 19.0 +/- 2.8 (urea), 12.1 +/- 3.5 (creatinine), 8.4 +/- 2.8 (gentamicin), 2.7 +/- 1.5 (vancomycin), and 1.7 +/- 0.8 (beta2M). The D/P concentration ratios and peritoneal CI(D) values for urea, creatinine, and gentamicin were significantly different from vancomycin and beta2M (repeated measures ANOVA, p < 0.05). Beta2-microglobulin peritoneal CI(D) was strongly related to gentamicin peritoneal CI(D) (r = 0.96, p < 0.05). CONCLUSION: Small molecular weight solutes have significantly greater D/P and peritoneal CI(D) than middle molecular weight solutes in NIPD. In NIPD, daily peritoneal CI(D) of beta2M is lower than that reported in continuous ambulatory PD. NIPD also results in lower drug CI(D) than that reported in continuous ambulatory PD studies.

Adult↗