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Dr Linda Hiebert, PhD Profesor |
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Research interests:
An important part of my research interests is the study of the pharmacokinetics and pharmacodynamics of heparin and related glycosaminoglycans following oral administration. This includes the evaluation of antithrombotic activity using venous and arterial thrombosis models in the rat, measurement of anticoagulant activity in plasma and measurement of chemical heparin in endothelium and other tissues. Studies into the mechanisms of absorption of oral heparin and other glycosaminoglycans are also underway. These studies will hopefully lead to the clinical use of oral heparin, making patient care more convenient as well as enabling other applications of heparin requiring long term administration.
In addition our laboratory is concerned with the assessment and protection of endothelial cells in culture from a variety of toxic agents. We have developed models of endothelial cell injury where cells are damaged by H2O2 , hypoxia, glucose and X-ray and alpha radiation. We have initiated endothelial cells from a variety of sources including aortic and brain microvascular cells from porcine and bovine sources and coronary arterial endothelial cells from rats. We are currently studying some of these toxic agents in commercially obtained primary human endothelial cells. Heparin and related compounds are being tested as protective agents in these models. In a related study we determining if heparin can prevent the loss of heparan sulphate and bFGF activity associated with hyperglycemic conditions. This preservation of heparan sulphate may reduce diabetic complications such as heart and kidney disease.
Recent publications:
L.M. Hiebert and Ping, T. (1997) Protective effect of dextran sulphate and heparin on adult rat cardiomyocytes damaged by free radicals. J. Mol. Cell. Cardiol., 29, 229-235.
L. M. Hiebert, S.M. Wice, L.B. Jaques, K.E. Williams, and J.M. Conly. (1999) Orally administered dextran sulphate is absorbed in HIV-positive individuals. J. Lab.Clin. Med.,133, 161-170.
L.M. Hiebert, S.M. Wice, T. Ping, R.E. Hileman, I. Capila and R.J. Linhardt. (2000) Tissue distribution and antithrombotic activity of unlabeled or 14 C-labeled porcine intestinal mucosal heparin following administration to rats by the oral route. Can. J. Physiol. Pharmacol.,78 , 307-320.
L.M. Hiebert, T. Ping and S.M. Wice (2000) Antithrombotic Activity of Orally Administered Low Molecular Weight Heparin (Logiparin) in a Rat Model. Haemostasis,30, 196-203.
L.M. Hiebert, S.M. Wice, T. Ping, D. Herr and V. Laux, (2001) Antithrombotic Efficacy in a Rat Model of the Low Molecular Weight Heparin, Reviparin Sodium, Administered by the Oral Route. Thrombosis & Haemostasis, 85, 114 -118.
J.I. Ram and L.M. Hiebert (2001) Marked Variation in Free Radical Injury Between Bovine and Porcine Endothelial Cells Cultured in Different Medium. In Vitro & Mol. Toxicol.,14, 209-217.
L.M. Hiebert (2002) Oral Heparins. Clinical Laboratory, 48, 111-116. (Review)
L.M. Hiebert, S.M. Wice, T. Ping, R.E. Hileman, T. Polat, R.J. Linhardt, (2002) Tissue distribution of [14 C] Sucrose octasulfate following oral administration to rats. Pharmaceut. Res.,19, 838-844.
L.M. Hiebert, 2002, Evidence that Orally Administered Heparins are Absorbed. In Thrombosis, >From Bench to Bedside (In press)
P.A.Thomas, B.L. Tracy, T. Ping, M. Wickstrom, N. Sidhu, L. Hiebert, (2002) The relative biological effectiveness (RBE) of 210 Po alpha particles vs. x-rays on lethality in bovine endothelial cells. International Journal of Radiation Biology (Accepted )