27 research outputs found

    Reducing the induction to abortion interval in termination of second trimester pregnancies: A comparison of mifepristone with laminaria tent

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    Objective: To determine whether mifepristone (RU486) is more effective than laminaria tent in shortening the induction-abortion interval in termination of second trimester pregnancies with gemeprost. Design: Prospective randomised comparative trial. Setting: Department of Obstetrics and Gynaecology in a University teaching hospital. Subjects: Sixty-two women undergoing termination of pregnancy in the second trimester. Interventions: The women were allocated at random to one of the two treatment groups. The first group received 600 mg of mifepristone 36 h before administration of gemeprost. In the second group, a medium-sized laminaria tent was inserted 12 h before gemeprost. The pregnancies in both groups were terminated with vaginal gemeprost, 1 mg every 3 h up to a maximum of 5 mg/day. Main outcome measures: Induction-abortion intervals, amount of gemeprost required, and incidence of side effects. Results: The median induction-abortion interval in the mifepristone group (7.5 h) was significantly shorter than that in the laminaria tent group (11 h) and significantly fewer gemeprost pessaries were required. There was no significant difference in the amount of narcotic analgesics required or the incidence of side effects between the two groups. Conclusions: Mifepristone is more effective than laminaria tent in shortening the induction-abortion interval in termination of second trimester pregnancies.link_to_subscribed_fulltex

    Human anti-dsDNA antibodies induce amplification loop of TGF-Ī²1, fibronectin and collagen type I in proximal renal tubular epithelial cells

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    Thursday Poster: TH-PO584BACKGROUND: Nephritis affects up to 60% of patients with systemic lupus erythematosus and is characterized by the production of anti-dsDNA antibodies and immune-mediated renal injury. Severity of tubulointerstitial fibrosis is a strong predictor of reduced renal survival. Fibronectin (FN) is amongst the matrix components showing early deposition during the process of tubulointerstitial fibrosis. This study investigates the mechanisms through which FN is induced in renal proximal tubular epithelial cells (PTEC) following stimulation with human anti-dsDNA antibodies, and its role in tubulointerstitial fibrosis of lupus nephritis. METHODS: Confluent growth-arrested PTEC were incubated with serum free medium (SFM), control IgG or human polyclonal anti-dsDNA antibodies (10Āµg/ml) for 24h in the presence or absence of Gƶ6976 or TGF-neutralizing antibody, and the synthesis of FN assessed. In separate studies, PTEC were stimulated with soluble FN to determine its effect on fibrotic processes. RESULTS: Control IgG had no effect on FN synthesis compared to SFM. Anti-dsDNA antibodies significantly increased cell-associated and soluble FN compared to SFM and control IgG (6.4- and 5.2-fold respectively for cell-associated FN; 1.85- and 1.62-fold respectively for soluble FN, P<0.01 for all). This was accompanied by significantly increased TGF-Ī²1 secretion (P<0.05), and increased PKC-Ī± (P<0.05) and PKC-Ī²II (P<0.01) but not PKC-Ī²I phosphorylation. Pre-treatment of PTEC with Gƶ6976 (20ĀµM) and TGF-neutralizing antibody (100g/ml) significantly suppressed anti-dsDNA antibody-induced FN (P<0.01 for both cell-associated and soluble FN). Incubation of PTEC with soluble FN significantly increased TGF-Ī²1 secretion and collagen type I synthesis in a dose-dependent manner (P<0.05 and P<0.01 respectively for 10Āµg/ml soluble FN). CONCLUSIONS: These results suggest that anti-dsDNA antibodies induce an amplification loop comprising TGF-Ī²1, FN and collagen type I in PTEC through PKC activation.link_to_OA_fulltex

    Anti-dsDNA antibodies induce epithelial-to-mesenchymal transition and fibrotic processes in human proximal renal tubular epithelial cells

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    Session - Pathobiology: Extracellular Matrix Biology, Fibrosis, Cell Adhesion: abstract TH-PO1034Meeting Theme: Curing Kidney DiseaseBACKGROUND: Tubulo-interstitial pathology predicts renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on proximal renal tubular epithelial cells (PTEC) and epithelial-to-mesenchymal transition (EMT). METHODS: Female NZBWF1/J mice at different stages of nephritis were sacrificed and kidneys harvested to assess the tubulo-interstitial changes over time. Growth-arrested primary human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10Ī¼g/ml for both) for periods up to 48h, and investigated for the synthesis of mediators of fibrosis and EMT. RESULTS: NZBWF1/J mice showed progressive tubular damage over time, as denoted by tubular atrophy, protein cast deposition, mononuclear cell infiltration and increasing tubulo-interstitial expression of fibronectin, collagen type I and fibroblast specific protein-1 (FSP-1). Anti-dsDNA antibodies significantly induced the synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced FSP-1 and Ī²-catenin synthesis (P<0.001 for both), which was accompanied by increased ERK and PKC-Ī± phosphorylation. Inhibition of ERK and PKC-Ī± activation using specific inhibitors reduced anti-dsDNA antibody induced EMT markers and fibronectin synthesis, and preserved normal PTEC phenotype. CONCLUSIONS: Our data demonstrate that anti-dsDNA antibodies contribute to tubulo-interstitial pathology in lupus nephritis via direct effects on PTEC which are mediated through ERK and PKC-Ī± activation.link_to_OA_fulltex
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