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In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from and Dynamic Effect-Exposure Relationship in Rat Plasma.
Mar Drugs
October 2022
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Glycosaminoglycan from (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa).
View Article and Find Full Text PDFThrombosis and Inflammation-A Dynamic Interplay and the Role of Glycosaminoglycans and Activated Protein C.
Front Cardiovasc Med
March 2022
Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Hemostasis, thrombosis, and inflammation are tightly interconnected processes which may give rise to thrombo-inflammation, involved in infectious and non-infectious acute and chronic diseases, including cardiovascular diseases (CVD). Traditionally, due to its hemostatic role, blood coagulation is isolated from the inflammation, and its critical contribution in the progressing CVD is underrated, until the full occlusion of a critical vessel occurs. Underlying vascular injury exposes extracellular matrix to deposit platelets and inflammatory cells.
View Article and Find Full Text PDFDirect oral anticoagulants are associated with limited damage of endothelial cells of the blood-brain barrier mediated by the thrombin/PAR-1 pathway.
Brain Res
September 2019
INSERM, U1059 Sainbiose, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France; Université de Lyon, Saint-Etienne F-42023, France.
Anticoagulant therapy presents iatrogenic effects such as intracerebral hemorrhage (ICH). The latest anticoagulants on the market, direct oral anticoagulants (DOACs) such as apixaban, dabigatran and rivaroxaban, are reported to cause less ICH than other anticoagulants. Next to the ICH area, the thrombin is accumulated and the blood-brain barrier (BBB) is opened.
View Article and Find Full Text PDFSelective Inhibition of PAR4 (Protease-Activated Receptor 4)-Mediated Platelet Activation by a Synthetic Nonanticoagulant Heparin Analog.
Arterioscler Thromb Vasc Biol
April 2019
From the Graduate Institute of Natural Products (Y.-C.L., J.-H.L., J.-Y.T., P.-H.K., M.-C.T., Y.-F.C., C.-C.W.), Kaohsiung Medical University, Taiwan.
Objective- PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II-binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect.
View Article and Find Full Text PDFThrombin-Induced Inflammation in Human Decidual Cells Is Not Affected By Heparin.
Reprod Sci
August 2017
1 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Objective: Thrombin (Thr) generation at the uteroplacental interface induces inflammation and weakens fetal membranes. Tissue factor (TF) is a powerful procoagulant that is increased by Thr in decidual cells (DCs). The TF expression may play an important role in modulating Thr-induced inflammation.
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