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Showing 1 to 20 of 141 for “"thrombin"”.
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UNDERSTANDING GENERALIZED ALLOSTERY IN THROMBIN
Thrombin is a critical drug target for chemotherapeutic and antithrombotic therapy development. Although many experiments have demonstrated that thrombin is a multifunctional allosteric enzyme, the exact mechanism of thrombin's allostery is still unclear and widely debated. This dissertation …
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Designing Allosteric Inhibitors of Thrombin
Thrombin is a key enzyme of the coagulation cascade exhibiting important roles in both pro-coagulation and anti-coagulation processes. Most clinically used anticoagulant drugs, including polymeric heparin, warfarin, hirudin, argatroban and the recently approved dabigatran, aim to reduce thrombin …
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Structural And Functional Studies On Thrombin Allostery
Thrombin is an allosteric serine protease endowed with important physiological functions in the blood. Once activated, α-thrombin plays procoagulant, prothrombotic, and anticoagulant functions in blood. Its important role in blood coagulation can be emphasized by the fact that thrombin interacts …
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RADIOSENSITIZING EFFECTS OF THROMBIN PEPTIDE TP508 ON MEDULLOBLASTOMA CANCER STEM CELLS
… relapse. Recently our laboratory showed that thrombin peptide TP508, a novel 23-amino acid investigational drug, protects normal neural stem cells from ionizing radiation damage. To determine whether the peptide would also protect brain CSCs from radiation damage, I examined the effects of …
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Role of Thrombin-Activatable Fibrinolysis Inhibitor in Breast Cancer Metastasis and Angiogenesis
… TAFIa is formed through cleavage by thrombin, plasmin or, by thrombin in complex with thrombomodulin. TAFIa is a carboxypeptidase, cleaving carboxyl terminal lysine residues from plasminogen binding sites on cell surface receptors, which are important in accelerating plasminogen …
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Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor in Non-Hepatic Cells
Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme that, once activated, attenuates fibrinolysis. TAFIa also possesses anti-inflammatory properties. Although liver is the main source of plasma TAFI, platelet-derived TAFI has also been reported. An alternatively …
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Immobilization Of The Anti-Thrombin DNA Aptamer: Attachment, Optimal Packing Density And Kinetics
… studies utilized the well-characterized anti-thrombin DNA aptamer. Investigations were conducted in order to ascertain effective methods of immobilization of the aptamer to silica and gold, the maximum packing density for which 100% of the aptamer activity is retained, and the binding kinetics …
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Discovery Of Inactive E* Conformations In Thrombin And Other Vitamin K- Dependent Clotting Proteases
… studying the kinetics of Na+ binding to human α-thrombin, we observed a biphasic mechanism of binding whose analysis led to the discovery that in the absence of Na+, the enzyme exists in dynamic equilibrium between two conformations, E* and E. Structural and kinetic studies indicate that E is the …
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Thrombin-Inhibiting Perfluorocarbon Nanoparticles: A New Class of Therapeutic for Acute Thrombosis Treatment and Diagnosis
… that a nanoparticle carrying potent direct thrombin inhibitors can advance the treatment of acute thrombosis arising from various cardiovascular pathologies. The thrombin-inhibiting nanoparticles presented herein are designed to focus the antithrombotic impact of direct thrombin inhibitors …
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Factors affecting the thrombin inhibiting activity of heparin when immobilised to hydrogels by covalent bonding
Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Applied Biological Sciences, 1986.
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Identification of a vascular smooth muscle cell transition associated with fibrous cap formation and induced by thrombin receptor activation
… caps of human plaques and its activation by thrombin in cultured human VSMCs induced expression of contractile, ECM and other genes characteristic of the fcVSMC state. Conclusions: My findings uncover a VSMC transition associated with fibrous cap formation in atherosclerosis that is also …
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Molecularly Targeted Nanoparticles for Modulation of Inflammatory Mediators in Atherosclerosis
<p>The enzyme thrombin has been demonstrated through experimental and clinical studies to play a crucial role in mediating both inflammation and thrombosis in atherosclerosis. The cellular effects of thrombin in promoting atherosclerosis involve the activation of signaling pathways that result in …
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Characterisation of protease activated receptors
The thrombin receptor is a seven transmembrane G-protein-coupled receptor that is activated by thrombin cleavage. In order to characterise the thrombin receptor three mouse monoclonal antibodies were isolated by using a recombinant fusion protein incorporating the extracellular domain of the human …
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Effect of platelet factors and thrombin on multiplication of human bone marrow mesenchymal stem cells cultured in low and high oxygen level in vitro
… examine effects of platelet-derived factors and thrombin on multiplication of adult human mesenchymal stem cells derived from bone marrow (hBMMSC) in a low or in a high oxygen environment in vitro. Hypothesis: It is hypothesized that PDF will have no effect on multiplication of BMMSC cultured in …
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Signaling Induced by Inflammatory Mediators in the Rodent Pulmonary Microvasculature
… of interendothelial junctions.</p> <p>Thrombin is a well-studied mediator that has been shown to be barrier-disruptive rapidly increases microvascular permeability. Sphingosin-1-phosphate (S1P) is a more novel, less understood mediator that has been shown to mediate basal vascular …
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Novel Sulfated 4-Hydroxycinnamic Acid Oligomers as Potent Anticoagulants
… creates a huge need for anticoagulation therapy. Thrombin and factor Xa have been prime targets for regulation of clotting through the direct and indirect mechanism of inhibition. This work investigates chemo-enzymatically prepared oligomers of 4-hydroxycinnamic acids (DHPs) as potential …
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The role of substance P in experimental intracerebral haemorrhage.
… that the post-ICH effects of intracerebral thrombin (which is known to play a major role in post-ICH secondary injury) are at least partly SP-mediated. Thrombin, similarly to SP, is known to play a deleterious role following both ischaemic stroke and traumatic brain injury. Previous research …
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MOLECULAR MODELING STUDIES OF HEPARIN AND HEPARIN MIMETICS BINDING TO COAGULATION PROTEINS
… positions. The interaction of heparin with antithrombin is the basis for anticoagulation therapy. Heparin accelerates the antithrombin mediated inhibition of factor Xa and thrombin by a conformational activation mechansism and bridging mechanism, respectively. The sequence specific …
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The effects of hypothermia and acidosis on Haemostasis
… STart®4 coagulometer was used to assess the prothrombin time (PT) and the activated partial thromboplastin time (APTT), the ROTEM® analyzer to assess thromboelastometry and the Fluoroscan Ascent to assess thrombin generation using calibrated automated thrombography (CAT). The results show a …
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The Requirement for Viable Platelets in the Coagulation of Heparinized Blood
… takes place. PF3 serves as a surface catalyst, thrombin is generated, and a fibrin clot is formed. The form in which PF3 is available is incidental to clot formation.</p> <p>When heparin is present, however, thrombin is neutralized as fast as it is formed. Quantities sufficient to induce fibrin …
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