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The specific monoca...
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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
(författare)
The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat
- Artikel/kapitelEngelska2007
Förlag, utgivningsår, omfång ...
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Ovid Technologies (Wolters Kluwer Health),2007
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:e1178237-45a2-4c18-86d8-d6c7c97c583b
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https://lup.lub.lu.se/record/968980URI
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https://doi.org/10.1097/01.tp.0000287541.53389.beDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori: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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Qi, Zhongquan
(författare)
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Pahlman, Clara
(författare)
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Veress, Bela
(författare)
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Bundick, Robert V.
(författare)
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Craggs, Robert I.
(författare)
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Holness, Elain
(författare)
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Edwards, Susan
(författare)
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Murray, Clare M.
(författare)
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Ferguson, Douglas
(författare)
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Kerry, Philip J.
(författare)
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Wilson, Elaine
(författare)
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Donald, David K.
(författare)
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Enheten för forskning kring njurfunktion och njursjukdomKirurgi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Transplantation: Ovid Technologies (Wolters Kluwer Health)84:9, s. 1191-11991534-60800041-1337
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Ekberg, Henrik
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Qi, Zhongquan
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Pahlman, Clara
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Veress, Bela
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Bundick, Robert ...
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Craggs, Robert I ...
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visa fler...
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Holness, Elain
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Edwards, Susan
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Murray, Clare M.
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Ferguson, Dougla ...
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Kerry, Philip J.
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Wilson, Elaine
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Donald, David K.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kirurgi
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Transplantation
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Lunds universitet