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Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2006 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 6, no 2, 305-12 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 6, no 2, 305-12 p.
Keyword [en]
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
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-21981DOI: 10.1111/j.1600-6143.2005.01186.xPubMedID: 16426314OAI: oai:DiVA.org:uu-21981DiVA: diva2:49754
Available from: 2007-03-06 Created: 2007-03-06 Last updated: 2017-12-07Bibliographically approved

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Johansson, H.Siegbahn, AgnetaElgue, GracielaKorsgren, OlleNilsson, Bo

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