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The new malononitrilamide immunosuppressant FK778 prolongs corneal allograft survival in the rat keratoplasty model.
Eye (Lond)
December 2007
Eye Hospital, Albert-Ludwigs University, Killianstr. 5, Freiburg, Germany.
Purpose: Aim of this study was to prove the efficacy and safety of the new malononitrilamide immunosuppressive FK778 in prolonging clear graft survival following allogeneic orthotopic keratoplasty in rats.
Methods: Sixty-seven penetrating keratoplasties were performed using Fisher and Lewis rats as donors and recipients, respectively: group 1 (n=11), allogeneic control without therapy; group 2 (n=12), syngeneic control; group 3 (n=11), mycophenolate mofetil (MMF) 40 mg/kg bodyweight; group 4 (n=12), FK778 5 mg/kg bodyweight; group 5 (n=12), FK778 10 mg/kg bodyweight; and group 6 (n=9), FK778 20 mg/kg bodyweight. Four animals in each group were killed for immunohistological evaluation on day 14.
Is the malononitrilamide FK778 better for the prevention of acute or chronic rejection?
Transplant Proc
March 2007
Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.
Objective: The aim of this study was to assess the efficacy of FK778 to prevent acute and chronic allograft rejection compared with other immunosuppressive agents.
Materials And Methods: Heterotopic Brown-Norway (BN)-to-Lewis rat cardiac transplantations and heterotopic BN-to-Lewis tracheal transplantations were performed to study acute heart rejection and the development of chronic obliterative airway disease (OAD), respectively. Recipients were treated with FK778, tacrolimus, MMF, or sirolimus for 10 days (acute rejection study) or 28 days (chronic OAD study) at varying doses.
Inhibition of restenosis development after mechanical injury: a new field of application for malononitrilamides?
Cardiology
October 2007
Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.
Objective: To investigate the efficacy of the malononitrilamide FK778 to prevent vascular smooth muscle cell (SMC) migration/proliferation, and vascular fibrosis, the key events in restenosis development using in vivo and in vitro studies.
Background: Since the high rate of restenosis after percutaneous transluminal coronary angioplasty limited its long-term success, the implementation of locally delivered antiproliferative/immunosuppressive agents became advantageous.
Methods: Rats underwent balloon denudation of the abdominal aorta and received sirolimus, tacrolimus, or FK778 for 28 days in varying doses.
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 PDFEfficacy of malononitrilamide FK778 in a preclinical model of small bowel transplantation.
Transplant Proc
January 2006
Department of Surgery, University of Pavia School of Medicine, I.R.C.C.S. Policlinico San Matteo Hospital, Pavia, Italy.
In a swine model of orthotopic small bowel transplantation, we assessed the efficacy of combined immunosuppressive therapy with low-dose tacrolimus plus FK778, compared with high-dose tacrolimus monotherapy. The small bowel was replaced in 23 piglets: group 1 (n = 5), no immunosuppression; group 2 (n = 12), oral tacrolimus to maintain whole blood trough levels between 15 and 25 ng/mL; and group 3 (n = 6), oral FK778 4 mg/kg/d, plus oral tacrolimus to maintain whole blood trough levels between 5 and 15 ng/mL. Follow-up time was limited to 60 days.
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