Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine.

Abstract:

:Leflunomide is a compound recently shown to reduce T and B cell-mediated responses in a number of experimental rat, mouse, and human systems. To explore its potential as an immunosuppressant, we studied leflunomide in 128 Brown-Norway/Lewis cardiac transplants and in 48 unoperated Lewis rats. At doses ranging from 0.63 mg/kg to 10 mg/kg given for 7 days, leflunomide significantly prolonged graft survival compared with controls. When cyclosporine or leflunomide was given for 21 days at a dose of 5 mg/kg, indefinite graft survival occurred in 3/6 animals receiving leflunomide but in none of the 21-day cyclosporine-treated animals. When acute rejection was allowed to develop for four days in untreated rats, leflunomide but not cyclosporine reversed the rejection, returning histology to a normal appearance by seven days. Alloantibody responses measured in microcytoxicity assays as well as total allospecific IgG and IgM in the rejecting animals also were returned to baseline levels by leflunomide but not cyclosporine. When both drugs were used together, a synergistic effect was observed at low doses of both drugs. Pharmacokinetics studies showed that their combined use for up to 28 days did not affect the trough levels of cyclosporine or cyclosporine elimination, suggesting that the synergistic effect was not caused by reduced elimination. The toxicity of each drug was negligible in a group of 32 rats receiving the drugs alone or in combination as measured by serial observation of general appearance, testing of serum ALT, AST, bilirubin, creatinine, white blood cell counts, hemoglobin, and gross necropsy appearance. Weight gain was slightly reduced by both drugs but combined drug use did not alter the pattern. The results of these experiments show leflunomide to be a potent, well-tolerated immunosuppressant, synergistic in its activity with cyclosporine, and would seem to encourage a closer look at this drug for potential use in man.

journal_name

Transplantation

journal_title

Transplantation

authors

Williams JW,Xiao F,Foster P,Clardy C,McChesney L,Sankary H,Chong AS

subject

Has Abstract

pub_date

1994-04-27 00:00:00

pages

1223-31

issue

8

eissn

0041-1337

issn

1534-6080

journal_volume

57

pub_type

杂志文章
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  • Selection and outcome of living donors for adult to adult right lobe transplantation.

    abstract:BACKGROUND:The shortage of cadaveric livers has sparked an interest in adult-to-adult living donor transplantation. Right lobe donor hepatectomy is frequently required to obtain a graft of adequate size for adult recipients. Careful donor selection is necessary to minimize complications and assure a functional graft. ...

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    authors: Marcos A,Fisher RA,Ham JM,Olzinski AT,Shiffman ML,Sanyal AJ,Luketic VA,Sterling RK,Olbrisch ME,Posner MP

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    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Abouna GM,al-Abdullah IH,Kelly-Sullivan D,Kumar MS,Loose J,Phillips K,Yost S,Seirka D

    更新日期:1995-06-15 00:00:00

  • Current status of clinical islet transplantation.

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    journal_title:Transplantation

    pub_type: 杂志文章,评审

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  • Determination of tolerance to self E alpha peptides by clonal elimination of H-2E reactive T cells and antigen presentation by H-2A molecules.

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    pub_type: 杂志文章

    doi:10.1097/00007890-199211000-00029

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  • Computer-assisted quantification of fibrosis in chronic allograft nephropaty by picosirius red-staining: a new tool for predicting long-term graft function.

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    doi:10.1097/01.TP.0000078899.62040.E5

    authors: Pape L,Henne T,Offner G,Strehlau J,Ehrich JH,Mengel M,Grimm PC

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  • Results of conversion from cyclosporine to azathioprine in cadaveric renal transplantation.

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    pub_type: 杂志文章

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    更新日期:1987-02-01 00:00:00

  • Mechanisms underlying continued survival of rat kidney allografts after a short period of chemical immunosuppression.

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    更新日期:1985-08-01 00:00:00

  • Improved phagocyte response by co-amoxiclav in renal transplant recipients.

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    authors: Cuffini AM,Tullio V,Giacchino F,Bonino A,Mandras N,Bianchi N,Roana J,Scalas D,Bonello F,Carlone NA

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  • A new micromethod for the detection of HL-A antigens on cultured human tumor cells.

    abstract::A rapid microcytotoxicity assay for the detection of HL-A antigens on tissue culture cells derived from human solid tumors is described. Tumor cells were prelabeled with 125Iododeoxyuridine. Isotopically labeled tumor cells were reacted with up to 37 highly selected HL-A antisera and diluted rabbit complement. Results...

    journal_title:Transplantation

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    authors: Fritze D,Kern DH,Drogemuller CR,Pilch YH

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  • Heavy Alcohol Use Among Deceased Donors Does Not Impact Recipient Outcomes After Liver Transplantation.

    abstract:BACKGROUND:Data on liver transplant (LT) outcomes using deceased donors with heavy drinking (HD) (>2 drinks per day) are scanty. METHODS:Using the United Network for Organ Sharing database (2002-2014), we examined outcomes after LT in adults comparing deceased HD donors with non-HD (ND) donors. RESULTS:Of 56 182 firs...

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    authors: Arora SS,Chahal KS,Axley P,Eckhoff DE,Kuo YF,Satapathy SK,Wiesner R,Singal AK

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  • Impact of renal posttransplantation amputation on allograft outcomes: a study of United States renal data system.

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    authors: Brar A,Jindal RM,Sumrani N,John D,Mondal Z,Tedla F,Salifu MO

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  • Ultrasound changes within the liver after total pancreatectomy and intrahepatic islet cell autotransplantation.

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    journal_title:Transplantation

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    doi:10.1097/TP.0b013e31817348d6

    authors: Ong SL,Pollard C,Rees Y,Garcea G,Webb M,Illouz S,Berry DP,Dennison AR

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  • Regulatory influence of thymopentin on splenic T cell sets of thymectomized and aged mice.

    abstract::Thymectomy of mice aged 6-8 weeks causes a disproportion of splenic T cell sets, the Ly123 set being relatively decreased and the Ly23 set relatively increased (Ly123 decrease: Ly23 increase). A similar disproportion of splenic T cell sets was found to occur spontaneously with advancing age (12-18 months). By PA-SRBC ...

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    pub_type: 杂志文章

    doi:10.1097/00007890-198511000-00010

    authors: Newcomb EW,Goldberg EH,de Sousa M,Goldstein G,Boyse EA,Scheid MP

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  • Isoenzyme characterization in isolated elevation of alkaline phosphatase after liver transplantation in children.

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  • Immunobiology of natural killer lymphocytes in transplantation.

    abstract::Natural killer (NK) lymphocytes are powerful effector cells of the peripheral immune system. NK cell functions are controlled by the expression of a variety of cell surface receptors with either inhibitory or activating roles. The genetic and functional diversity of this repertoire of receptors and the role of human l...

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  • Elevated Urinary Matrix Metalloproteinase-7 Detects Underlying Renal Allograft Inflammation and Injury.

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    doi:10.1097/TP.0000000000000867

    authors: Ho J,Rush DN,Krokhin O,Antonovici M,Gao A,Bestland J,Wiebe C,Hiebert B,Rigatto C,Gibson IW,Wilkins JA,Nickerson PW

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    pub_type: 杂志文章

    doi:10.1097/01.tp.0000128837.07640.ae

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  • Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.

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    pub_type: 杂志文章

    doi:10.1097/01.TP.0000065283.98275.FE

    authors: Nery JR,Nery-Avila C,Reddy KR,Cirocco R,Weppler D,Levi DM,Nishida S,Madariaga J,Kato T,Ruiz P,Schiff E,Tzakis AG

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  • Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

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  • Factors influencing the patterns of T lymphocyte allorecognition.

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    doi:10.1097/01.TP.0000045034.48833.51

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