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  • Ekberg, HenrikLund University,Lunds universitet,Enheten för forskning kring njurfunktion och njursjukdom,Kirurgi,Forskargrupper vid Lunds universitet,Renal Research Unit,Surgery,Lund University Research Groups (author)

The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat

  • Article/chapterEnglish2007

Publisher, publication year, extent ...

  • Ovid Technologies (Wolters Kluwer Health),2007

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  • LIBRIS-ID:oai:lup.lub.lu.se:e1178237-45a2-4c18-86d8-d6c7c97c583b
  • https://lup.lub.lu.se/record/968980URI
  • https://doi.org/10.1097/01.tp.0000287541.53389.beDOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Background. In a search for immunosuppressive drugs having novel mechanisms, monocarboxylate transporter (MCT-1) inhibitors were identified that markedly inhibited immune responses. Here, we report the effects of AR-C117977, a potent MCT-1 inhibitor, on alloimmune responses in the rat. Methods. In vitro activity was determined in a rat mixed lymphocyte response (MLR). In vivo activity was tested in a graft versus host response (GVHR) and in both high (DA to PVG) and low (PVG to DA) responder cardiac allograft models. To assess induction of donor-specific suppression recipients of allogeneic hearts surviving longer than 100 days received a second transplant either of the same donor strain or a third-party donor strain. Effects on chronic graft rejection were assessed histologically by evaluating vasculopathy in long-term surviving grafts and in an obliterative bronchiolitis (013) model. Results. AR-C117977 inhibited the rat MLR and was more potent than cyclosporin A (CsA). In the rat GVHR model, AR-C117977 gave a dose-related inhibition. In the high responder cardiac allograft model, graft survival in excess of 100 days was achieved with AR-C117977 compared with 20 days with CsA and all the long-term survivors exhibited donor-specific suppression on retransplantation. In the low responder model, both AR-C117977 and CsA induced survival in excess of 100 days. Histology of the long-term surviving grafts suggested reduced vasculopathy associated with chronic rejection. Furthermore, AR-C117977 inhibited the occlusion of transplanted trachea in a 013 model. Conclusion. This report describes a MCT-1 specific inhibitor having immunosuppressive activity on alloinimune responses and inducing donor-specific suppression.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Qi, Zhongquan (author)
  • Pahlman, Clara (author)
  • Veress, Bela (author)
  • Bundick, Robert V. (author)
  • Craggs, Robert I. (author)
  • Holness, Elain (author)
  • Edwards, Susan (author)
  • Murray, Clare M. (author)
  • Ferguson, Douglas (author)
  • Kerry, Philip J. (author)
  • Wilson, Elaine (author)
  • Donald, David K. (author)
  • Enheten för forskning kring njurfunktion och njursjukdomKirurgi (creator_code:org_t)

Related titles

  • In:Transplantation: Ovid Technologies (Wolters Kluwer Health)84:9, s. 1191-11991534-60800041-1337

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