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Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation.

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Johansson, H. Goto, M Dufrane, Denis [UCL] Siegbahn, A Elgue, G. Gianello, Pierre [UCL] Nilsson, B

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.

Document type Article de périodique (Journal article) – Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
Access type Accès libre
Publication date 2006
Journal information "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons" - Vol. 6, no. 2, p. 305-12 (2006)
Peer reviewed yes
issn 1600-6135
Publication status Publié
Affiliations UCL - MD/FSIO - Département de physiologie et pharmacologie
UCL - MD/CHIR - Département de chirurgie
UCL - (SLuc) Service de chirurgie et transplantation abdominale
UCL - (SLuc) Service d'orthopédie et de traumatologie de l'appareil locomoteur
MESH Subject Anticoagulants - therapeutic use ; Cadaver ; Dextran Sulfate - therapeutic use ; Heparin - therapeutic use ; Humans ; Inflammation - prevention & control ; Intraoperative Complications - prevention & control ; Islets of Langerhans Transplantation - physiology ; Molecular Weight ; Partial Thromboplastin Time ; Tissue Donors
Links
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Bibliographic reference Johansson, H. ; Goto, M ; Dufrane, Denis ; Siegbahn, A ; Elgue, G. ; et. al. Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation.. In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Vol. 6, no. 2, p. 305-12 (2006)
Permanent URL http://hdl.handle.net/2078.1/21737