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Newer Immunosuppressive Drugs A Review

TLDR
This review focuses on those drugs that have been shown to have immunosuppressive activity in patients and shows a statistically significant reduction in the incidence of acute rejection produced by these new drugs, which has not been accompanied by increases in infection and malignancy rates.
Abstract
In recent years, many new immunosuppressive drugs have been discovered and developed for clinical use in transplantation. This review focuses on those drugs (leflunomide, mycophenolate mofetil, sirolimus, tacrolimus) that have been shown to have immunosuppressive activity in patients. Different anti-interleukin-2 receptor antibodies are also reviewed as an example of a resurgence of development in the area of monoclonal antibodies. The price for reducing the incidence of allograft rejection by improved immunosuppression was thought to be a proportional increase in the incidence of infection and malignancy. Data from Phase III clinical trials of new immunosuppressants, however, show a statistically significant reduction in the incidence of acute rejection produced by these new drugs, which has not been accompanied by increases in infection and malignancy rates. The wide array of new drugs offers the opportunity to use combinations that block different pathways of immune activation while at the same time selecting drug combinations with nonoverlapping toxicity profiles so that doses of each single drug can be reduced below toxicity levels. The immunosuppressive therapy for patients can be tailored according to their individual needs.

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Journal ArticleDOI

Stent-Based Delivery of Sirolimus Reduces Neointimal Formation in a Porcine Coronary Model

TL;DR: Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.
Journal ArticleDOI

Mechanisms of clinically relevant drug interactions associated with tacrolimus.

TL;DR: Progress can be expected from studies evaluating potential pharmacokinetic interactions caused by herbal preparations and food components, the exact biochemical mechanism underlying tacrolimus toxicity, and the potential of inhibition of CYP3A and P-glycoprotein to improve oral bioavailability and to decrease intraindividual variability of tacolimus pharmacokinetics.
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Immunosuppressive and Anti-Inflammatory Mechanisms of Triptolide, the Principal Active Diterpenoid from the Chinese Medicinal Herb Tripterygium wilfordii Hook. f.

TL;DR: Characterisation of the terpenoids present in extracts of Tripterygium identified triptolide, a diterpenoid triepoxide, as responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects observed in vitro.
Journal ArticleDOI

Manipulating Immune Responses with Immunosuppressive Agents that Target NFAT

TL;DR: This work was supported by the National Institutes of Health, Deutsche Forschungsgemeinschaft, and the Arthritis Foundation, and A. R. was a Stohlman Scholar of the Leukemia Society of America.
References
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Journal ArticleDOI

Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes

TL;DR: The results suggest that calcineurin is involved in a common step associated with T cell receptor and IgE receptor signaling pathways and that cyclophilin and FKBP mediate the actions of CsA and Fk506 by forming drug-dependent complexes with and altering the activity of calcineURin-calmodulin.
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The mechanism of action of cyclosporin A and FK506

TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
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Chemistry and biology of the immunophilins and their immunosuppressive ligands.

TL;DR: Defining the biological roles of this emerging family of receptors and their ligands may illuminate the process of protein trafficking in cells and the mechanisms of signal transmission through the cytoplasm.
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Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.

TL;DR: This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients.
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