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At least 559 records · Page 31Linked to original sources
PubMed1995

Mycophenolic acid, an inhibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells.

Mycophenolic acid (MPA), an inhibitor of IMP dehydrogenase and de novo GTP biosynthesis, also has immunosuppressive activity. The effect of MPA on nitric oxide (NO) production by rodent brain vascular endothelial cells in culture was investigated. MPA inhibited NO production by mouse and rat brain endothelial cells that had been stimulated with a combination of interferon-gamma and tumor necrosis factor-alpha. The 50% inhibitory concentration (EC50) was in the range of 0.5-1.0 microM. However, MPA had no effect on basal NO production in mouse brain vascular endothelial cells. Brequinar, an inhibitor of de novo pyrimidine synthesis, had no effect on NO production in cytokine stimulated endothelial cells. Guanosine, which can act as a salvage pathway precursor for GTP biosynthesis, reversed the inhibitory effect of MPA in a dose-dependent fashion. We suggest that inducible NO synthase activity is dependent on GTP level and can be blocked by curtailing IMP dehydrogenase activity.

Animals↗
PubMed2001

[Rapamycin: a new immunosuppressive agent capable of inhibiting chronic rejection?].

Chronic rejection represents the most common cause of transplanted graft loss in the long term. Rapamycin (sirolimus), and it's derivate RAD, are new and potent, immunosuppressive drugs. They inhibit cell proliferation driven by various growth factors. These drugs were successfully tested in some experimental models of the chronic rejection. Results of the first clinical trials have defined rapamycin pharmacokinetics and proved immunosuppressive efficacy. Rapamycin acts synergistically with cyclosporin A. The side effects are a dose-dependent thrombocytopenia and leukopenia but the most frequent is hyperlipidemia. The question, if rapamycin and RAD inhibit development of chronic rejection in man, will be solved by the prospective clinical trials over years.

Chronic Disease↗
PubMed2000

Current and future trends in the use of immunosuppressive agents in patients with uveitis.

Therapeutic trials for uveitis are seldom performed because of the relative rarity of the disease and its heterogeneity. Promising new approaches to therapy include cytokine or cytokine receptor inhibition; cytokine addition (alpha-interferon or interleukin-10); novel anti-metabolites; combination therapies; intravenous immunoglobulin; intravitreally inserted corticosteroid implants; and oral tolerance. Additional modalities or targets that deserve further testing include T-cell subsets, adhesion molecules, accessory molecules in antigen presentation, novel inflammatory mediators, inducers of apoptosis, photodynamic therapy, and neuroprotective agents.

Apoptosis↗