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Immunotherapy for De Novo renal transplantation: what's in the pipeline?
Drugs
January 2007
Division of Nephrology, Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, São Paulo, Brazil.
Immunosuppressive drugs have been traditionally developed to prevent acute rejection and to improve short-term kidney transplant outcomes. There is still a medical need to improve outcomes among subgroups of patients at higher risk for graft loss and to reduce cardiovascular, infectious and malignancy-associated morbidity and mortality, and improve long-term adherence. Several new immunosuppressive agents and formulations are undergoing clinical investigation and are discussed in this review.
View Article and Find Full Text PDFFK778: new cellular and molecular mechanisms of action.
Transplant Proc
April 2006
Department of Cardiovascular Surgery, University Heart Center, Hamburg, Germany.
Purpose: The new malononitrilamide FK778 is currently being evaluated as an immunosuppressant for organ transplantation. Its main mechanism is inhibition of a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms of action on different cell types involved in acute and chronic allograft rejection.
View Article and Find Full Text PDFMechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV infection in rats.
Transplantation
January 2005
Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
Background: FK778 is a malononitrilamide, a class of immune suppressive compounds with antiviral features and experimental activity in chronic rejection, a potentially interesting combination for organ transplantation. The goal of this project was to study the tolerability, immune suppressive efficacy, and anti-cytomegalovirus (CMV) activity of FK778 and to assess the in vivo relevance of its previously described inhibition of de novo pyrimidine synthesis.
Methods: Heart transplants were performed in rats (Brown Norway [BN] to Lewis) and treated with varying doses of FK778 or leflunomide for 28 days.
FK778, a novel immunosuppressive agent, reduces early adhesion molecule up-regulation and prolongs cardiac allograft survival.
Transpl Int
February 2005
Department of Cardiovascular Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
The adhesion molecules, P-selectin, ICAM-1, and VCAM-1 are important mediators of T-cell adhesion and T-cell co-stimulation. We investigated the effect of the malononitrilamide FK778 on cardiac allograft survival, acute allograft rejection, and adhesion molecule up-regulation in a heterotopic, cardiac transplantation model. Rats received low- or high-dose FK778 or no treatment.
View Article and Find Full Text PDFFK778 attenuates lymphocyte-endothelium interaction after cardiac transplantation: in vivo and in vitro studies.
Transplantation
July 2004
Department of Cardiovascular Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Background: The malononitrilamide FK778 is a novel derivate of leflunomide and interacts with T- and B-cell function by inhibiting de novo pyrimidine synthesis. We investigated the effects of FK778 upon acute cardiac allograft rejection and upon adhesion molecule upregulation in experimental transplantation and by using in vitro cell culture.
Methods: Heterotopic, abdominal cardiac transplantations were performed in the Brown Norway (BN) to Lewis (Lew) rat model.
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