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- W2047201414 abstract "247 Background: Chronic rejection (CR) with graft vasculopathy has emerged as the major cause of graft loss, with no or little therapeutic options. The role of antigen-dependant immune responses has not been clarified yet, however macrophages as well as T-cells have been shown to be involved. The alkaloid Sinomenine (SN) is known for anti-inflammatory, anti-rheumatic and immunomodulatory effects. We recently have shown novel anti-macrophage, T cell and EC effects of SN in acute cardiac graft rejection and now have investigated the effects of SN in in the F344/Lewis cardiac model for CR. Materials and Methods: Lewis recipients of F344 hearts were transplanted heterotopically into Lewis rats treated with CsA (5 mg/kg, i.m.) for 10 days posttransplant. Recipients were later treated with SN alone (15 mg/kg, orally), cyclosporine alone (CsA, 5 mg/kg, i.m.) or in combination (n = 5 per group) as summarized below. Grafts were analyzed by light microscopy (H&E, v. Gieson), serum samples by FACS for IgG and IgM. (Table)Results: Allografts of groups 1-3 showed progressive endothelialitis, moderate to dense mononuclear cell (MNC) infiltrates with subepicardial infarcts, edema and myocardial fibrosis in conjunction with elicited IgM and IgG. Vascular changes and MNC infiltrates were also detected in grafts after SN- (groups 4-6) or CsA-treatment (groups 7-9), but to a lesser extent. By contrast, SN/CsA effectively improved graft morphology with the absence of vascular changes and only mild MNC infiltration. No transplant arteriosclerosis was seen in long-term surviving rats (100d) despite high titers of IgM and IgG. Conclusion: These studies demonstrate for the first time the therapeutic value of SN in a model of CR. SN alone stabilizes CR and in combination with low dose CsA prevents vascular changes, which warrants further evaluation. Immunohistological studies are under current investigation.Table" @default.
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- W2047201414 date "1999-05-01" @default.
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- W2047201414 title "IMMUNOMODULATORY EFFECTS OF SINOMENINE IN THE F344/LEWIS MODEL OF CHRONIC TRANSPLANT REJECTION" @default.
- W2047201414 doi "https://doi.org/10.1097/00007890-199905150-00271" @default.
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