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Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts.

Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Research Abstract Details 

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  • Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Abstract Text:

    a pileggiA Pileggi,r d molanoR D Molano,s songS Song,e zahrE Zahr,s sanjoseS Sanjose,s villateS Villate,c wasserfallC Wasserfall,c ricordiC Ricordi,m a atkinsonM A Atkinson,l inverardiL Inverardi,

    Alpha-1 antitrypsin (AAT) is a serine protease inhibitor able to prevent diabetes onset in nonobese diabetic (NOD) mice and to prolong islet allograft survival in a nonautoimmune murine model. In this study, we explored the effect of chronic administration of human AAT (hAAT) on allogeneic (C57BL/6) islet graft survival in spontaneously diabetic female NOD mice. Mice received intraperitoneal treatment with saline, Prolastin (1 or 2 mg/mouse) or Aralast (2 mg/mouse) on days -1, 0, 3, 6, and 9. Saline-treated mice rejected the grafts 10.0 +/- 2.5 days after transplantation (n = 9). Prolastin 1 mg (n = 9) and 2 mg (n = 3) resulted in rejection on 8.7 +/- 1.4 (not significant) and 13.0 +/- 4.3 days (P < .03), respectively. Aralast-treated mice showed prolongation of graft survival (13 +/- 5.9 days; n = 5; P < .03). Notably, repeated administrations of either hAAT formulation led to sudden death of a proportion of treated animals. Collectively, our preliminary data indicate that prolongation of islet allograft survival in the stringent autoimmune diabetic NOD mouse model can be achieved with hAAT monotherapy. The death of a proportion of treated animals may be consequent to immunization to hAAT and lethal hypersensitivity. Interestingly, this phenomenon was not observed in a non-autoimmune mouse strain (C57BL/6) despite extended hAAT treatment (>100 days).

    Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Publishing Authors By Initials

    a pileggiA Pileggi,rd molanoRD Molano,s songS Song,e zahrE Zahr,s sanjoseS Sanjose,s villateS Villate,c wasserfallC Wasserfall,c ricordiC Ricordi,ma atkinsonMA Atkinson,l inverardiL Inverardi,

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    Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Transplantation proceedings

    VOLUME: 40

    Page Numbers: 457-8

    Journal Abbreviation:

    ISSN: 0041-1345

    DAY: 31

    MONTH: Mar

    YEAR: 2008

    Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Information

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    LANGUAGE: eng

    NlmUniqueID: 243532

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    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Transplant Proc

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