An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
Clotting time of PLASMA mixed with a THROMBIN solution. It is a measure of the conversion of FIBRINOGEN to FIBRIN, which is prolonged by AFIBRINOGENEMIA, abnormal fibrinogen, or the presence of inhibitory substances, e.g., fibrin-fibrinogen degradation products, or HEPARIN. BATROXOBIN, a thrombin-like enzyme unaffected by the presence of heparin, may be used in place of thrombin.
Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.
A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.
Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.
Two small peptide chains removed from the N-terminal segment of the alpha chains of fibrinogen by the action of thrombin during the blood coagulation process. Each peptide chain contains 18 amino acid residues. In vivo, fibrinopeptide A is used as a marker to determine the rate of conversion of fibrinogen to fibrin by thrombin.
A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.
Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure.
A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
A sulfated plasma protein with a MW of approximately 66kDa that resembles ANTITHROMBIN III. The protein is an inhibitor of thrombin in plasma and is activated by dermatan sulfate or heparin. It is a member of the serpin superfamily.
Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot.
A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Two small peptide chains removed from the N-terminal segment of the beta chains of fibrinogen by the action of thrombin. Each peptide chain contains 20 amino acid residues. The removal of fibrinopeptides B is not required for coagulation.
Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation.
The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy.
Laboratory tests for evaluating the individual's clotting mechanism.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
The rate dynamics in chemical or physical systems.
Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Agents that cause clotting.
Agents that prevent clotting.
Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.
Use of HIRUDINS as an anticoagulant in the treatment of cardiological and hematological disorders.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.
Formation and development of a thrombus or blood clot in the blood vessel.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.
The natural enzymatic dissolution of FIBRIN.
A class of receptors that are activated by the action of PROTEINASES. The most notable examples are the THROMBIN RECEPTORS. The receptors contain cryptic ligands that are exposed upon the selective proteolysis of specific N-terminal cleavage sites.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.
Stable blood coagulation factor involved in the intrinsic pathway. The activated form XIa activates factor IX to IXa. Deficiency of factor XI is often called hemophilia C.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.
Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.
Peptides composed of between two and twelve amino acids.
A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
A proteolytic enzyme obtained from the venom of fer-de-lance (Bothrops atrox). It is used as a plasma clotting agent for fibrinogen and for the detection of fibrinogen degradation products. The presence of heparin does not interfere with the clotting test. Hemocoagulase is a mixture containing batroxobin and factor X activator. EC 3.4.21.-.
Clotting time of PLASMA recalcified in the presence of excess TISSUE THROMBOPLASTIN. Factors measured are FIBRINOGEN; PROTHROMBIN; FACTOR V; FACTOR VII; and FACTOR X. It is used for monitoring anticoagulant therapy with COUMARINS.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Proteins prepared by recombinant DNA technology.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
An enzyme fraction from the venom of the Malayan pit viper, Agkistrodon rhodostoma. It catalyzes the hydrolysis of a number of amino acid esters and a limited proteolysis of fibrinogen. It is used clinically to produce controlled defibrination in patients requiring anticoagulant therapy. EC 3.4.21.-.
A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed)
Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.
Fibrinogens which have a functional defect as the result of one or more amino acid substitutions in the amino acid sequence of normal fibrinogen. Abnormalities of the fibrinogen molecule may impair any of the major steps involved in the conversion of fibrinogen into stabilized fibrin, such as cleavage of the fibrinopeptides by thrombin, polymerization and cross-linking of fibrin. The resulting dysfibrinogenemias can be clinically silent or can be associated with bleeding, thrombosis or defective wound healing.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
A fibrin-stabilizing plasma enzyme (TRANSGLUTAMINASES) that is activated by THROMBIN and CALCIUM to form FACTOR XIIIA. It is important for stabilizing the formation of the fibrin polymer (clot) which culminates the coagulation cascade.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
Soluble protein fragments formed by the proteolytic action of plasmin on fibrin or fibrinogen. FDP and their complexes profoundly impair the hemostatic process and are a major cause of hemorrhage in intravascular coagulation and fibrinolysis.
Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.
A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.
An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occurring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I (see FIBRIN) and ANTITHROMBIN III appear to be of major importance.
Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.
Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.
A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.
Activated form of factor VII. Factor VIIa activates factor X in the extrinsic pathway of blood coagulation.
The process of cleaving a chemical compound by the addition of a molecule of water.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Compounds that contain a 1-dimethylaminonaphthalene-5-sulfonyl group.

Role of thrombin receptor in breast cancer invasiveness. (1/5662)

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism.  (+info)

Activation of stimulus-specific serine esterases (proteases) in the initiation of platelet secretion. I. Demonstration with organophosphorus inhibitors. (2/5662)

The effect of organophosphorus inhibitors of serine esterases (proteases) on secretion from washed rabbit platelets was examined. Five noncytotoxic stimuli were employed: collagen, thrombin, heterologous anti-platelet antibody (in the absence of complement), rabbit C3 bound to zymosan, and platelet activating factor derived from antigen-stimulated, IgE-sensitized rabbit basophils. Diisoprophyl phosphofluoridate, three series of p-nitrophenyl ethyl phosphonates, and a series of cyclohexyl phenylalkylphosphonofluridates were all found to be inhibitory to the platelet secretion. These are irreversible inhibitors of serine proteases but in this system were only inhibitory if added to the platelets concurrently with the stimuli. Pretreatment of either the platelets or the stimuli with the inhibitors followed by washing, was without effect on the subsequent reaction. This suggested the involvement of stimulus-activatable serine proteases in the secretory process. The concept was supported by finding that nonphosphorylating phosphonates or hydrolyzed phosphonates or phosphonofluoridates were without inhibitory action. The effect of a series of phosphonates or phosphonoflouridates in inhibiting each stimulus exhibited a unique activity-structure profile. The demonstration of such unique profiles with four series of inhibitors for each of the five stimuli was interpreted as demonstrating that a specific activatable serine protease was involved in the platelet secretory response to each stimulus.  (+info)

Exosites 1 and 2 are essential for protection of fibrin-bound thrombin from heparin-catalyzed inhibition by antithrombin and heparin cofactor II. (3/5662)

Assembly of ternary thrombin-heparin-fibrin complexes, formed when fibrin binds to exosite 1 on thrombin and fibrin-bound heparin binds to exosite 2, produces a 58- and 247-fold reduction in the heparin-catalyzed rate of thrombin inhibition by antithrombin and heparin cofactor II, respectively. The greater reduction for heparin cofactor II reflects its requirement for access to exosite 1 during the inhibitory process. Protection from inhibition by antithrombin and heparin cofactor II requires ligation of both exosites 1 and 2 because minimal protection is seen when exosite 1 variants (gamma-thrombin and thrombin Quick 1) or an exosite 2 variant (Arg93 --> Ala, Arg97 --> Ala, and Arg101 --> Ala thrombin) is substituted for thrombin. Likewise, the rate of thrombin inhibition by the heparin-independent inhibitor, alpha1-antitrypsin Met358 --> Arg, is decreased less than 2-fold in the presence of soluble fibrin and heparin. In contrast, thrombin is protected from inhibition by a covalent antithrombin-heparin complex, suggesting that access of heparin to exosite 2 of thrombin is hampered when ternary complex formation occurs. These results reveal the importance of exosites 1 and 2 of thrombin in assembly of the ternary complex and the subsequent protection of thrombin from inhibition by heparin-catalyzed inhibitors.  (+info)

Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. (4/5662)

Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the alpha-subunit of the heterotrimeric G protein Gq do not aggregate and degranulate but still undergo shape change after activation through thromboxane-A2 (TXA2) or thrombin receptors. In contrast to thrombin, the TXA2 mimetic U46619 led to the selective activation of G12 and G13 in Galphaq-deficient platelets indicating that these G proteins mediate TXA2 receptor-induced shape change. TXA2 receptor-mediated activation of G12/G13 resulted in tyrosine phosphorylation of pp72(syk) and stimulation of pp60(c-src) as well as in phosphorylation of myosin light chain (MLC) in Galphaq-deficient platelets. Both MLC phosphorylation and shape change induced through G12/G13 in the absence of Galphaq were inhibited by the C3 exoenzyme from Clostridium botulinum, by the Rho-kinase inhibitor Y-27632 and by cAMP-analogue Sp-5,6-DCl-cBIMPS. These data indicate that G12/G13 couple receptors to tyrosine kinases as well as to the Rho/Rho-kinase-mediated regulation of MLC phosphorylation. We provide evidence that G12/G13-mediated Rho/Rho-kinase-dependent regulation of MLC phosphorylation participates in receptor-induced platelet shape change.  (+info)

Regulation of the activities of thrombin and plasmin by cholesterol sulfate as a physiological inhibitor in human plasma. (5/5662)

Thrombin and plasmin, both of which are serine proteases in the plasma of vertebrates, play essential roles in blood clotting and fibrinolysis, respectively, and regulation of their activities is important to suppress the excessive reactions within the vascular network and to prevent tissue injury. Along with the peptidic inhibitors belonging to the serpin family, we found that cholesterol sulfate (CS), which is present at the concentration of 2.0+/-1.2 nmol/ml in human plasma, was a potent inhibitor of both plasma thrombin and plasmin. Thrombin, as determined both using a chromogenic substrate and the natural substrate, fibrinogen, was inactivated upon reaction with CS in a dose-dependent manner, but not in the presence of the structurally related steroid sulfates, I3SO3-GalCer and II3NAalpha-LacCer, suggesting that both the sulfate group and the hydrophobic side chain of CS are necessary for the inhibitory activity of CS. Preincubation of thrombin with CS at 37 degrees C for 10 min was required to achieve maximum inhibition, and virtually complete inhibition was achieved at a molar ratio of CS to thrombin of 18:1. CS-treated thrombin had the same Km and a lower Vmax than the original enzyme, and a higher molecular weight. The molecular weight and activity of the original enzyme were not observed on the attempted separation of the CS-treated enzyme by gel permeation chromatography and native PAGE, indicating that the inactivation of thrombin by CS is irreversible. In contrast, CS was readily liberated from the enzyme by SDS-PAGE, suggesting that hydrophobic interactions are involved in the CS-mediated inactivation of thrombin. When acidic lipids were reacted with thrombin after dissolving them in DMSO, I3SO3-GalCer, steroid sulfates and II3NAalpha-LacCer, as well as CS, but not SDS and sodium taurocholate, exhibited inhibitory activity, probably due to micellar formation facilitating interaction between thrombin and negatively charged lipids. On the other hand, plasmin, as determined using a chromogenic substrate, was more susceptible to acidic lipids than thrombin. CS, I3SO3-GalCer and II3NAalpha-LacCer, all of which are present in serum, inhibited the activity of plasmin in aqueous media, as well as in DMSO-mediated lipid solutions. Thus, acidic lipids in plasma were demonstrated to possess regulatory activity as endogenous detergents toward both enzymes for blood clotting and fibrinolysis.  (+info)

Unexpected crucial role of residue 225 in serine proteases. (6/5662)

Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr in more than 95% of nearly 300 available sequences. Proteases with Y225 (like some blood coagulation and complement factors) are almost exclusively found in vertebrates, whereas proteases with P225 (like degradative enzymes) are present from bacteria to human. Saturation mutagenesis of Y225 in thrombin shows that residue 225 affects ligand recognition up to 60,000-fold. With the exception of Tyr and Phe, all residues are associated with comparable or greatly reduced catalytic activity relative to Pro. The crystal structures of three mutants that differ widely in catalytic activity (Y225F, Y225P, and Y225I) show that although residue 225 makes no contact with substrate, it drastically influences the shape of the water channel around the primary specificity site. The activity profiles obtained for thrombin also suggest that the conversion of Pro to Tyr or Phe documented in the vertebrates occurred through Ser and was driven by a significant gain (up to 50-fold) in catalytic activity. In fact, Ser and Phe are documented in 4% of serine proteases, which together with Pro and Tyr account for almost the entire distribution of residues at position 225. The unexpected crucial role of residue 225 in serine proteases explains the evolutionary selection of residues at this position and shows that the structural determinants of protease activity and specificity are more complex than currently believed. These findings have broad implications in the rational design of enzymes with enhanced catalytic properties.  (+info)

Injury-induced gelatinase and thrombin-like activities in regenerating and nonregenerating nervous systems. (7/5662)

It is now widely accepted that injured nerves, like any other injured tissue, need assistance from their extracellular milieu in order to heal. We compared the postinjury activities of thrombin and gelatinases, two types of proteolytic activities known to be critically involved in tissue healing, in nonregenerative (rat optic nerve) and regenerative (fish optic nerve and rat sciatic nerve) neural tissue. Unlike gelatinases, whose induction pattern was comparable in all three nerves, thrombin-like activity differed clearly between regenerating and nonregenerating nervous systems. Postinjury levels of this latter activity seem to dictate whether it will display beneficial or detrimental effects on the capacity of the tissue for repair. The results of this study further highlight the fact that tissue repair and nerve regeneration are closely linked and that substances that are not unique to the nervous system, but participate in wound healing in general, are also crucial for regeneration or its failure in the nervous system.  (+info)

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort. (8/5662)

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.  (+info)

TY - JOUR. T1 - Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin. T2 - Potential role of protein Z as a powerful determinant of coagulation assays. AU - Choi, Qute. AU - Kim, Ji Eun. AU - Hyun, Jungwon. AU - Han, Kyou Sup. AU - Kim, Hyun Kyung. PY - 2013/7. Y1 - 2013/7. N2 - Background The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. Methods The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. ...
To the best of our knowledge, this is the first study investigating TG-related parameters following PCC administration in acute trauma patients. PCC therapy resulted in significantly higher ETP than in patients who received fibrinogen concentrate only or no coagulation therapy at all and, importantly, this was sustained over the first 3 to 4 days following PCC administration. AT was significantly lower in the FC-PCC group from ER admission until 3 to 4 days later, reaching a nadir on day 2. Hemostasis relies on a delicate balance between pro- and anticoagulant factors, and between thrombin potential and thrombin inhibition potential. This balance may have been impaired in the FC-PCC group, during a period when fibrinogen levels were increased above the normal range; similar findings have been reported in previous studies [34, 35]. The overall picture is increased thrombin potential (day 1 to day 4), increased substrate for coagulation (that is, fibrinogen reaching a plateau on day 4) and ...
The aim of this thesis is to evaluate thrombin generation in patients with thrombophilia (Paper I), in patients with venous thromboembolism (Paper II), in healthy women during the menstrual cycle (Paper III), in patients with liver disease (Paper IV) and in patients with mild deficiency of factor VII (Paper V).. For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak).. The cohorts for Papers I and II are part of a larger cohort (The LInköping Study on Thrombosis, LIST), which included 516 consecutive patients who ...
The aim of this thesis is to evaluate thrombin generation in patients with thrombophilia (Paper I), in patients with venous thromboembolism (Paper II), in healthy women during the menstrual cycle (Paper III), in patients with liver disease (Paper IV) and in patients with mild deficiency of factor VII (Paper V).. For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak).. The cohorts for Papers I and II are part of a larger cohort (The LInköping Study on Thrombosis, LIST), which included 516 consecutive patients who ...
TGA Testing Products. Thrombin Generation Assay (TGA) is a more global downstream read out for the kinetics of thrombin generation during initiation, amplification and down regulation of thrombin formation from activation of proteins in the coagulation cascade, like PKA and FXIa. Technothrombin® TGA is a complete fluorogenic tool for a broad range of applications and is therefore a universal assay kit for analyzing and researching the function of the hemostatic system.. ...
The present study demonstrates that thrombin, the central protease of the coagulation cascade, can be functionally imaged in vivo by using a novel NIR thrombin-activatable reporter. In vitro experiments first confirmed that the probe was specifically activated by endogenous thrombin within blood. In experimental murine thrombosis models, thrombin activation of the probe resulted in focal NIRF signal enhancement in occlusive and nonocclusive thrombi. Thrombin activity was detected within acute and subacute thrombi with the use of probe injections at clinically relevant time points, did not require preinjection of the probe, and could be rapidly detected in vivo by fluorescence reflectance imaging systems.. Although in vitro thrombin activity has been detected for many years with the use of chromogenic or fluorogenic substrates,18,19⇓ current experimental results now show that thrombin activity can be imaged in vivo by using the NIRF-activatable probe scheme previously developed in our ...
TY - JOUR. T1 - Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. AU - Hu, Liang. AU - Lee, Merlin. AU - Campbell, Wendy. AU - Perez-Soler, Roman. AU - Karpatkin, Simon. PY - 2004/11/1. Y1 - 2004/11/1. N2 - Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor growth and metastasis experiments in mice by the use of hirudin, a highly potent specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor implantation in nude or syngeneic mice, following subcutaneous injection of 2 human and 2 murine tumors. Hirudin induced a considerable lag period in the appearance of tumor growth, compared with phosphate-buffered saline (PBS) treatment, but had no effect on established tumor nodule growth in vivo or on tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor nodule compared with no effect with PBS treatment. Greater protection was noted with longer duration of treatment. Tumor seeding into blood was ...
BACKGROUND: Heparin is of limited value as an antithrombotic drug in the presence of platelet activation and residual thrombus. Greater anticoagulant activity can be achieved in vivo with more specific thrombin inhibitors. Heparin may also increase the risk of bleeding by an effect on platelets that is independent of its thrombin inhibitory activity. METHODS AND RESULTS: The pharmacodynamic and pharmacokinetic effects of a novel thrombin inhibitor, argatroban, were examined alone and in combination with aspirin in normal male volunteers. Argatroban induced a dose-dependent prolongation of the thrombin time and the activated partial thromboplastin time (aPTT). aPTT had returned to its pretreatment value 1 hour after stopping the infusion of argatroban. Six male subjects received an infusion of 1 micrograms/kg/min argatroban after the administration of two doses of 162.5 mg aspirin or a matching placebo. At this dose, aspirin decreased serum thromboxane B2 by a mean of 99% and prolonged the bleeding time
In this Cochrane meta-analysis, researchers analyzed the overall efficacy and safety of direct thrombin inhibitors, compared to warfarin or LMWH, in preventing VTE after orthopedic surgeries (hip and knee arthroplasty). In14 studies involving over 20,000 participants, they found no difference in efficacy between direct thrombin inhibitors, warfarin, or LMWH, but did find higher mortality and bleeding in the thrombin group compared to LMWH (but no difference between the thrombin group and warfarin) (abstract). The timing of the thrombin inhibitors also matters, as pre-operative dosing results in fewer VTEs but likely higher bleeding. Dabigatran is the oral direct thrombin inhibitor that is currently approved in Canada and throughout Europe, but US FDA approval is pending.. ...
Thrombin demonstrates a high level of allosteric regulation.[2] Allosterism in thrombin is regulated by the exosites 1 and 2 and the sodium binding site. A recent patent review has shown that the general consensus among researchers is that allosteric inhibitors may provide a more regulatable anticoagulant.[3] Some of the allosteric inhibitors discovered include DNA aptamers,[3] benzofuran dimers,[4] benzofuran trimers,[5] as well as polymeric lignins.[6] A new sulfated β-O4 lignin (SbO4L) has been discovered which has shown a dual mechanism of action for anti-thrombosis. This SbO4L shows allosteric inhibition of thrombin for fibrinogen, while providing a competitive inhibition of thrombin interaction with platelet glycoprotein Ibα (GPIbα), thereby preventing thrombin mediated platelet aggregation.[7] However, despite the growing interest and the advances in allosterism, no allosteric thrombin inhibitor has yet reached the stage of clinical trials.. ...
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Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90s. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric ...
Background Venous thromboembolism (VTE) is a common complication in patients with cancer receiving chemotherapy. Currently no anticoagulant is approved for VTE prophylaxis in this setting. Semuloparin is an ultra-LMWH generated through a highly selective depolymerization of heparin which protects the antithrombin (AT) binding site in order to improve the benefit/risk ratio compared to existing anitcoagulants.. Aims We studied in vitro the mechanism of action of semuloparin on the inhibition of thrombin generation (TG) of human platelet poor plasma (PPP) triggered by human pancreatic cancer cells BXPC3. We compared the antithrombotic efficiency of semuloparin to that of enoxaparin and the specific AT-dependent factor Xa inhibitor fondaparinux.. Materials and methods BXPC3 cells were suspended in PPP spiked with clinically relevant concentrations of semuloparin, enoxaparin and fondaparinux. The endogenous thrombin potential (ETP) and the mean rate index (MRI) of the propagation phase of TG were ...
Patients with a significant bleeding history and normal routine laboratory tests are labelled as having unclassified bleeding disorder (UBD). Approximately one third of patients with acute deep vein thrombosis (DVT) have no risk factor identified and are labelled idiopathic. The experiments conducted herein investigate whether the phospholipid composition of the platelet membrane is contributory to the clinical phenotype. The ability of platelets and microvesicles to support thrombin generation was investigated using a thrombin generation assay tailored to be sensitive to the phospholipid membrane. Peak thrombin generation supported by washed platelets and microvesicles was reduced in UBD patients compared with healthy controls. Peak thrombin and velocity index were increased in patients with DVT. To determine whether changes in thrombin generation could be attributed to native aminophospholipids in the platelet membrane, Phosphatidylserine (PS) and Phosphatidylethanolamine (PE) were measured by ...
Purpose: The purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock. Material and Methods: Twenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis. Results: The rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis. Conclusions: Patients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not ...
TY - JOUR. T1 - Thrombin induces proliferation of osteoblast-like cells through phosphatidylcholine hydrolysis. AU - Suzuki, Atsushi. AU - Kozawa, Osamu. AU - Shinoda, Junji. AU - Watanabe, Yasuko. AU - Saito, Hidehiko. AU - Oiso, Yutaka. PY - 1996/7/1. Y1 - 1996/7/1. N2 - We examined the effect of thrombin on phosphatidylcholine-hydrolyzing phospholipase D activity in osteoblast-like MC3T3-E1 cells. Thrombin stimulated the formation of choline dose dependently in the range between 0.01 and 1 U/ml, but not the phosphocholine formation. Diisopropylfluorophosphate (DFP)-inactivated thrombin had little effect on the choline formation. The combined effects of thrombin and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C-activating phorbol ester, on the choline formation were additive. Staurosporine, an inhibitor of protein kinases, had little effect on the thrombin-induced formation of choline. Combined addition of thrombin and NaF, an activator of heterotrimeric GTP-binding protein, did not ...
We have developed an aptamer-based microarray for human thrombin detection exploiting two non-overlapping DNA thrombin aptamers recognizing different exosites of the target protein. The 15-mer aptamer (TBA1) binds the fibrinogen-binding site, whereas the 29-mer aptamer (TBA2) binds the heparin binding domain. Extensive analysis on the complex formation between human thrombin and modified aptamers was performed by Electrophoresis Mobility Shift Assay (EMSA), in order to verify in solution whether the chemical modifications introduced would affect aptamers/protein recognition. The validated system was then applied to the aptamer microarray, using the solid phase system devised by the solution studies. Finally, the best procedure for Sandwich Aptamer Microarray (SAM) and the specificity of the sandwich formation for the developed aptasensor for human thrombin were optimized.
Thrombin (EC 3.4.21.5, fibrinogenase, thrombase, thrombofort, topical, thrombin-C, tropostasin, activated blood-coagulation factor II, blood-coagulation factor IIa, factor IIa, E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is produced in the liver and is ...
Thrombin is a serine protease that in humans is encoded by the F2 gene. Thrombin is an intriguing coagulation protease demonstrating an array of effects on endothelial cells, vascular smooth muscle cells (VSMC), monocytes, and platelets, all of which are involved in the pathophysiology of atherosclerosis. There is mounting evidence that thrombin acts as a powerful modulator of many processes like regulation of vascular tone, permeability, migration and proliferation of VSMC, recruitment of monocytes into the atherosclerotic lesions, induction of diverse pro-inflammatory markers, and all of these are related to the progression of cardiovascular disease. Recent studies in transgenic mice models indicate that the deletion of the natural thrombin inhibitor heparin cofactor II promotes an accelerated atherogenic state. The combined evidence points to thrombin as a pivotal contributor to vascular pathophysiology. Considering the clinical development of selective anticoagulants including direct ...
Our affordable bovine thrombin is used to defibrinate plasma, producing serum matrixes to be used as controls and standards or in polyclonal antibody production. Our high purity thrombins are used to defibrinate plasma as well as to cleave fusion proteins tags. Available in research and bulk size quantities.
Background: Pregnant women are at increased risk of venous thrombosis compared to non-pregnant women. Epidemiological and laboratory data suggest that hypercoagulability begins in the first trimester but it is unknown exactly how early in pregnancy this develops. The mechanisms that result in a prothrombotic state may involve oestrogens and progestogens. Methods: Plasma samples were taken prior to conception and five times in early pregnancy, up to Day 59 gestation, from 22 women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy. Thrombin generation, free Protein S, Ddimer, Fibrinogen, factor VIII, estradiol and progesterone were measured. To counter inter-individual variability, the change in laboratory measurements between the pre-pregnant and pregnant state were measured over time. Results: Peak thrombin, Endogenous Thrombin Potential, Velocity Index and fibrinogen significantly increased, and free Protein S significantly ...
In vivo, thrombin serves as both the primary stimulus for thrombosis and subsequent thrombus growth on a template of activated platelets or platelet-derived procoagulant microparticles (15-17). Our group has shown that patients with clinically stable coronary artery disease (CAD) have evidence of increased thrombin activity and generation (18)as do those with unstable angina (19,20)and acute MI (21)in whom the abnormality persists for weeks to months after the presenting event (22). Consistent with prior observations (23), patients in this study exhibited increased thrombin generation despite treatment with UFH (10,18,24,25). The limitations associated with UFH administration may, at least in part, be the result of its relative inaccessibility to clot-bound thrombin and an inability to effectively neutralize factor Xa-mediated procoagulant activity (26).. The thrombogenicity of atheromatous plaques and dysfunctional endothelial cells is strongly influenced by tissue factor which is considered ...
TY - JOUR. T1 - Hyperglycemia-induced thrombin formation in diabetes. T2 - The possible role of oxidative stress. AU - Ceriello, A.. AU - Giacomello, R.. AU - Stel, G.. AU - Motz, E.. AU - Taboga, C.. AU - Tonutti, L.. AU - Pirisi, M.. AU - Falleti, E.. AU - Bartoli, E.. PY - 1995. Y1 - 1995. N2 - Diabetes is characterized by the existence of a thrombosis-prone condition, possibly related to hyperglycemia. However, the mechanism linking hyperglycemia to the activation of the coagulation cascade is still unclear. It has been recently suggested that diabetes is accompanied by increased oxidative stress. In this work, the possibility that oxidative stress may be involved in the hyperglycemia-induced coagulation activation has been evaluated. Prothrombin fragment 1 + 2 (F1+2), which represents a reliable marker of the amount of thrombin released in the circulation, has been chosen for studying thrombin formation in vivo. In nine type II diabetic patients and in seven healthy control subjects, ...
Thrombin Inhibitor-Direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin
The major finding of the present study is that GIT1 is a novel mediator for thrombin signal transduction in ECs modulating thrombin-induced changes in cell shape and EC barrier function. Specifically, we show that GIT1 is recruited to FAs in a RhoA-dependent manner. GIT1 is phosphorylated on tyrosine residues in an agonist-dependent manner that requires Rho kinase, Src, and FAK activation. Finally, an important role for GIT1 in EC rounding and endothelial barrier recovery was demonstrated by GIT1 depletion. Based on these findings, we propose a model for thrombin-induced changes in EC function mediated by GIT1 (Figure 8). Specifically, binding of thrombin to its receptor initiates a F-actin-dependent EC contraction involving activation of RhoA and Rho kinase. GIT1 then translocates to FAs, where in concert with FAK and Src, it modulates FA (dis)assembly contributing to changes in cell shape. An intact F-actin cytoskeleton is necessary for GIT1 recruitment to FAs, as disruption of the F-actin ...
Abstract. Abstract 41Background. Therapy with by-passing agents (BPA) in patients with hemophilia and inhibitors still lacks a laboratory test able to assess
In an effort to reduce the risks of a possible iatrogenic transmission of bovine spongiform encephalitis (BSE) through the use of bovine-derived medicinal products, we patented in the USA in 1999 a polysaccharide from brown algae, endowed with interesting pharmacological activities: (a) concentration-dependent inhibition of thromboplastin or cephalin-kaolin-induced thrombin generation from platelets, (b) concentration-dependent inhibition of thrombin-induced platelet aggregation, (c) thrombin has hypotensive effect, which was blunted and zeroed by our fucansulfate in a dose-dependent way, (d) when aortae are stimulated with thrombin, they become stickier for polymorphonucleated leukocytes (PMNs); our fucansulfate decreased concentration-dependently, PMNs sticking to autologous rabbit aortae, (e) dose-dependent inhibition of thrombin-induced thrombosis. All the above data suggest that our fucansulfate could be a heparin substitute endowed with antithrombotic and anti-inflammatory activities, devoid or
1000 G indicates 1000 Genome; CAD/MI, coronary artery disease/myocardial infarction; CI, confidence interval; ETP, endogenous thrombin potential; FVIII, factor VIII; IVW, inverse variance weighting; OR, odds ratio; NA, not available; PAI, plasminogen activator inhibitor; SNP, single-nucleotide polymorphism; tPA, tissue-type plasminogen activator; vWF, von Willebrand factor; WGLM, weighted generalized linear regression model; and WM, weighted median method. ...
The binding of thrombin to fibrin is thought to be an important mechanism by which thrombi exhibit procoagulant activity; however, the extent to which other procoagulants are associated with thrombi has not been previously defined. This study was designed to determine whether clotting factors other than thrombin are bound to whole-blood clots and can thereby contribute to significant procoagulant activity. Clots formed in vitro from human blood exhibited minimal thrombin activity when incubated in plasma depleted of vitamin K-dependent factors by barium-citrate adsorption, as indicated by increases in the concentration of fibrinopeptide A (FPA), a marker of fibrin formation, to 72 nM after 30 min. Incubation of clots in barium-absorbed plasma repleted with 0.9 microM human prothrombin under the same conditions resulted in marked increases in the concentration of FPA (, 1,000 nM) and clotting by 30 min. The increases in FPA were attributable to activation of the added prothrombin by ...
The present study shows that PAR1 acts as a cofactor for thrombin activation of PAR4 on human platelets and other cells and provides a mechanistic basis to understand PAR1-PAR4 synergy. By selectively ablating the PAR1 signal with a potent inhibitor of the PAR1 tethered ligand,23 we determined that PAR4 is activated at surprisingly low concentrations of thrombin on human platelets. By inhibiting the ability of thrombin to associate with PAR1, we show that PAR1 plays a critical helper function in assisting PAR4 activation by thrombin. A cleavage-sensitive PAR4-Ab was used to demonstrate that PAR1 and PAR4 exist as a complex on human platelets. Stable hetero-oligomerization between PAR1 and PAR4 was also observed in recombinant systems and did not require prior cleavage by thrombin.. The present work supports earlier observations with PAR1 and PAR4 pepducin antagonists7 and blocking antibodies8,10,31 that targeting only PAR1 and not PAR4 may have a partial therapeutic effect. Thus, a combination ...
STA THROMBIN 10,Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium.,medicine,medical supply,medical supplies,medical product
Thrombin is a serine protease that in humans is encoded by the F2 gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the coagulation
Thrombin - Get up-to-date information on Thrombin side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Thrombin
Thrombin can be used outside the body exploiting its serine cleaving properties. As a biochemical tool, it is used to fuse proteins.. It can also be used in the food industry to bind different types of meat together. The coagulating properties enable meat manufacturers to blend different types of meat like fish and beef to form a new meat mixture.. In the medical field, it can be used during surgery where there is blood loss and if it is not handled carefully it can lead to hemorrhage. Its been useful in many other important functions in the field of science.. Topical administration of aqueous thrombin helps in hemostasis. Therefore, it is also essential in maintaining normal balance and flow of nutrients and oxygen in the body.. ...
TY - JOUR. T1 - Thrombin-induced gap formation in confluent endothelial cell monolayers in vitro. AU - Laposata, Michael. AU - Dovnarsky, D. K.. AU - Shin, H.. PY - 1983. Y1 - 1983. N2 - When thrombin is incubated with confluent monolayers of human umbilical vein endothelial cells in vitro, there is a change in the shape of the endothelial cells that results in gaps in the monolayer disrupting the integrity of the endothelium and exposing the subendothelium. Using a grid assay to measure this phenomenon, we observed that up to 80% of the surface area once covered by cells was uncovered after a 15-min incubation with 10-2 U/ml (10-10 M) thrombin. The effect was apparent within 2 min and did not remove cells from the surface of the culture dish. The gaps in the monolayer completely disappeared within 2 hr after exposure to thrombin. The effect of thrombin was inhibited by preincubation of thrombin with hirudin or antithrombin III plush heparin or by preincubation of the monolayers with dibutyryl ...
Thrombin removel His tag protein digestion - posted in Protein and Proteomics: After thrombin cutting of his - tagged protein , Iam unable to purify the protein from by using size exclusion chromatography .always showing the contamination of thrombin residuals as per sds page .i am using PBS buffer for throbin cutting . could you please give any suggestion to remove throbin removal ?
Thrombin in surgery is commonly used in a variety of situations (3-10). The majority of the thrombin used today is of bovine origin, causing concern about adverse reactions (e.g., antibody formation against human FV leading to bleeding episodes (11,12), and transmission of bovine prions possibly causing vCJD). To generate thrombin from a Cited by:
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Abstract. Pediatric patients with acute lymphoblastic leukemia (ALL) are at an increased risk of thromboembolic events. Potential responsible mechanisms includ
Author: Bode, W.; Genre: Journal Article; Published in Print: 2006-03; Keywords: thrombin; coagulation; specificity; anion-binding exosite; fibrin; thrombomodulin; cofactors; crystal structures; Title: Structure and interaction modes of thrombin
A prothrombotic state is one of the hallmarks of advanced cancer, and thromboembolic disease contributes significantly to the mortality of cancer patients (reviewed in1). Tissue factor (TF), the cellular activator of the coagulation cascade, is central to the hypercoagulable state of cancer patients and responsible for local thrombin generation and fibrin deposition in the tumor stroma. TF also triggers remote thrombotic complications involving procoagulant TF+ microparticles2 with potential contribution from other cancer procoagulants (reviewed in3). TF-dependent coagulation generates thrombin and induces pleiotrophic cellular effects of thrombin on platelets through G protein-coupled protease-activated receptors (PARs)4 as well as thrombin-initiated vascular-protective signaling of the endogenous activated protein C-EPCR-PAR1 pathway.5 Direct signaling by TF-associated proteases are mediated by the binary TF-VIIa enzyme complex that activates PAR2 or the ternary TF-VIIa-Xa coagulation ...
Intestinal epithelium produces active thrombin, which plays an unsuspected shield role against gut microbial community living on mucosal surface.
Methods of tissue engineering combine cells and biomaterials to grow regenerative tissue. Because of its excellent biocompatibility fibrin has become a frequently used matrix in tissue engineering. To date, autologous fibrinogen has usually been polymerised with bovine thrombin. Bovine thrombin, however can cause severe immunological side effects and in some cases patients even died after recurrent use. The objective of this study was to explore the practicability of obtaining autologous thrombin from a single patient in an adequate concentration and amount. After fibrinogen was cryoprecipitated from about 200 ml of freshly-frozen plasma, thrombin was isolated from the supernatant through ion-exchange chromatography. The thrombin was first bound to Sephadex A-50, then eluated using a salt buffer and finally purified from the salt through Sephadex G-50. To provide a system for clinical application a prototype of a single use unit which allowed preparation in a closed system was developed. With ...
Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface. ...
Dang, Q. D., and Di Cera, E. (1997) Nat. Biotechnol. 15, 891-895; and Le Bonniec, B. F., MacGillivray, R. T., and Esmon, C. T. (1991) J. Biol. Chem. 266, 13796-13803). Optimal binding interactions witin thrombin occur only if these tripeptide substrates contain an amino acid residue in the (D)-configuration, such as (d)Phe at P3 (Blomback, B., Blomback, M., Olsson, P., Svendsen, L., and Aberg, G. (1969) Scand. J. Clin. Lab Invest SuppI 107, 59-61), which mimics the natural Pgresidue in FpA (Ni, F., Meinwald, Y. C, Vasquez, M., and Scheraga, H. A. (1989) Biochemistry 28, 3094-3105; Stubbs, M. T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S. R., and Bode, W. (1992) Eur. J. Biochem. 206, 187-195; and Martin, P. D., Robertson, W., Turk, D., Huber, R., Bode, W., and Edwards, B. F. (1992) J. Biol. Chem. 267, 7911-7920). However, these minimalistic peptide substrates probe only the active site apparatus of thrombin and related binding events, which were found to be mildly sensitive to ...
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Unless specified otherwise, MP Biomedicals products are for laboratory research use only, not for human or clinical use. For more information, please contact our customer service department ...
A purified therapeutic grade thrombin is described which is essentially free of lipid envelope viruses, has a specific activity of about 2200 NIH units per milligram of protein to about 3200 NIH units per milligram of protein, is essentially homogeneous and may be produced on a commercial-scale. The thrombin is acceptable from human administration.
The liver synthesizes the majority of pro- and anti-coagulant and fibrinolytic proteins, and during liver dysfunction synthesis of these proteins is reduced. The end point of conventional hemostatic tests, such as the prothrombin time (PT), occurs when only 5% of thrombin generation (TG) has taken place and is not sensitive to the effects of natural anti-coagulants. The aim of this study was to determine whether TG in the presence of thrombomodulin (TM) provides more useful information about coagulation potential, in comparison to the PT. Analysis was performed on ST Genesia, a novel TG analyzer from Diagnostica Stago. TG was measured using STG-Thromboscreen, a reagent containing an intermediate concentration of human tissue factor (TF) ± rabbit TM to account for anti-coagulant protein C (PC) activity. Platelet-poor plasma (PPP) samples were from the Intensive Care Study of Coagulopathy-2 (ISOC-2), which recruited patients admitted to critical care with a prolonged PT (3 seconds above the reference
Thrombin antibody LS-C658904 is an unconjugated rabbit polyclonal antibody to human Thrombin (F2 / Prothrombin ). Validated for WB.
Direct thrombin inhibitorsEdit. Main article: direct thrombin inhibitor. Another type of anticoagulant is the direct thrombin ... It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection ... An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in ... thrombin) inhibitor, and the factor Xa inhibitors rivaroxaban and apixaban. Clinical trials have shown them therapeutically ...
Each molecule of Factor Xa can generate 1000 molecules of thrombin. This large burst of thrombin is responsible for fibrin ... amplification of the procoagulant signal by thrombin generated on the TF-bearing cell and 3) propagation of thrombin generation ... It acts by cleaving prothrombin in two places (an arg-thr and then an arg-ile bond), which yields the active thrombin. This ... In stage 3, thrombin generation, Factor XIa activates free Factor IX on the surface of activated platelets. The activated ...
Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, Zavodszky P, Arlaud GJ, Schumaker VN (May 1992). "Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex". Biochemistry. 31 (17): 4254-62. doi:10.1021/bi00132a015. PMID 1533159 ...
Protein HtrA2, also known as Omi, is a mitochondrially-located serine protease. The human protein Serine protease HTRA2, mitochondrial is 49kDa in size and composed of 458 amino acids. The peptide fragment of 1-31 amino acid is the mitochondrial transition sequence, fragment 32-133 amino acid is propertied, and 134-458 is the mature protein Serine protease HTRA2, mitochondrial, and its theoretical pI of this protein is 6.12.[10] HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and a carboxy-terminal PDZ domain, which is characteristic of the HtrA family. The PDZ domain preferentially binds C-terminus of the protein substrate and modulate the proteolytic activity of the trypsin-like protease domain.[11] ...
Seol JH, Woo SK, Jung EM, Yoo SJ, Lee CS, Kim KJ, Tanaka K, Ichihara A, Ha DB, Chung CH (April 1991). "Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product". Biochemical and Biophysical Research Communications. 176 (2): 730-6. doi:10.1016/s0006-291x(05)80245-1. PMID 2025286 ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.[1] Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion process.[1] As a result, protease inhibitors that interfere with digestion activity have an antinutritional effect. Therefore, trypsin inhibitor is considered an anti-nutritional factor or ANF.[3] Additionally, trypsin inhibitor partially interferes with chymotrypsin function. Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and muscles, are ...
Cholecystokinin (CCK) is a unique peptide released by the duodenal "I cells" in response to chyme containing high fat or protein content. Unlike secretin, which is an endocrine hormone, CCK actually works via stimulation of a neuronal circuit, the end-result of which is stimulation of the acinar cells to release their content.[5] CCK also increases gallbladder contraction, causing release of pre-stored bile into the cystic duct, and eventually into the common bile duct and via the ampulla of Vater into the second anatomic position of the duodenum. CCK also decreases the tone of the sphincter of Oddi, which is the sphincter that regulates flow through the ampulla of Vater. CCK also decreases gastric activity and decreases gastric emptying, thereby giving more time to the pancreatic juices to neutralize the acidity of the gastric chyme ...
"Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding ... Tellez C, Bar-Eli M (May 2003). "Role and regulation of the thrombin receptor (PAR-1) in human melanoma". Oncogene. 22 (20): ... Ogino Y, Tanaka K, Shimizu N (Nov 1996). "Direct evidence for two distinct G proteins coupling with thrombin receptors in human ... Vu TK, Hung DT, Wheaton VI, Coughlin SR (Mar 1991). "Molecular cloning of a functional thrombin receptor reveals a novel ...
Treatment is with oral anticoagulants (not heparin as heparin acts via anti-thrombin 3 which is lost in the proteinuria so it ... Antithrombin III counteracts the action of thrombin. Thrombosis usually occurs in the renal veins although it can also occur in ...
Thrombin Sistem Koagulasi Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a ... Thrombin can also bind to cells via the PAR1receptor to trigger several other inflammatory responses, such as production of ...
Hirose, Ruby (1934). "The Second Phase of Thrombin Action: Fibrin Resolution". American Journal of Physiology.. ... She did research on blood clotting and Thrombin, allergies, and researched cancer using antimetabolites. ... "Nature of Thrombin and Its Manner of Action".[11] A paper based on this thesis was later published in the American Journal of ... Physiology in 1934 with the title "The Second Phase of Thrombin Action: Fibrin Resolution".[12] ...
Direct thrombin inhibitors provides an excellent example of negative allosteric modulation. Allosteric inhibitors of thrombin ... "Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities". Proceedings of the National Academy of ...
Orange or grey/yellow "tiger" Top: thrombin, a rapid clot activator, for stat serum testing ...
Steven FS, Griffin MM (1982). "Inhibition of thrombin cleavage of fibrinogen by polyestradiol phosphate; interaction with the ...
Li, J. J.; Huang, Y. Q.; Basch, R.; Karpatkin, S. (February 2001). "Thrombin induces the release of angiopoietin-1 from ... "Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and ...
Lundblad, R.L., Kingdon, H.S. and Mann, K.G. (1976). „Thrombin". Methods Enzymol. 45: 156-176. PMID 1011989.. CS1 одржавање: ... Baughman, D.J. (1970). „Thrombin assay". Methods Enzymol. 19: 145-157.. *↑ Magnusson, S. (1970). „Bovine prothrombin and ...
Thrombin is a potent platelet activator, acting through Gq and G12. These are G protein coupled receptors and they turn on ... They aggregate in response to thrombin, but not to ADP, serotonin, nor adrenaline, as platelets do.[65][66] ... Tissue factor also binds to factor VII in the blood, which initiates the intrinsic coagulation cascade to increase thrombin ... Thrombin also promotes secondary fibrin-reinforcement of the platelet plug. Platelet activation in turn degranulates and ...
These platelets have thrombin receptors on their surfaces that bind serum thrombin molecules[1] which in turn convert soluble ... It is formed by the action of the protease thrombin on fibrinogen which causes it to polymerize. The polymerized fibrin ... From Fibrinogen to Fibrin with the help of Thrombin and Factor VIII. ...
Direct thrombin inhibitorsEdit. Main article: Direct thrombin inhibitor. Another type of anticoagulant is the direct thrombin ... An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in ... thrombin, and other coagulation factors.[84] Heparin can be used in vivo (by injection), and also in vitro to prevent blood or ... that reverses effect of dabigatran by binding to both free and thrombin-bound dabigatran.[111][112] Andexanet alfa is a ...
... versus thrombin treatment, which may implicate CASS4 mediated signaling in platelet hyperreactivity.[25] ... "Phosphoproteomic analysis of platelets activated by pro-thrombotic oxidized phospholipids and thrombin". PLOS ONE. 9 (1): ...
Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves ... The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the ... Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin, resulting in fibrinolysis. The ... Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of ...
"Thrombin and platelet activation". Chest. 124 (3 Suppl): 18S-25S. doi:10.1378/chest.124.3_suppl.18S. PMID 12970120 ...
二价(英语:Direct thrombin inhibitor#Bivalent): 水蛭素(比伐卢定(英语:Bivalirudin)、地西卢定、来匹卢定(英语:Lepirudin)、水蛭素). 单价(英语:Direct thrombin ... Synthesis of Thrombin inhibiting Heparin mimetics without side effects. Nature. 1999, 398 (6726): 417-422. ISSN 0028-0836. PMID ... Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence. ... 直接凝血
1994). „Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel ... Hoffman M, Church FC (1993). „Response of blood leukocytes to thrombin receptor peptides.". J. Leukoc. Biol. 54 (2): 145-51. ... Tellez C, Bar-Eli M (2003). „Role and regulation of the thrombin receptor (PAR-1) in human melanoma.". Oncogene. 22 (20): 3130- ... 1996). „Cloning and identification of regulatory sequences of the human thrombin receptor gene.". J. Biol. Chem. 271 (42): ...
Their saliva contains a local anesthetic, thrombin inhibitor, antibiotic properties and a histamine-like vasodilator. These ...
Brass LF (September 2003). "Thrombin and platelet activation". Chest 124 (3 Suppl): 18S-25S. PMID 12970120. doi:10.1378/chest. ...
... activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using factor XIII) into a ... Upon activation by thrombin (factor IIa), it dissociates from the complex to interact with factor IXa in the coagulation ...
Roles of platelets and factor XI in the initiation of blood coagulation by thrombin. Thromb. Haemost.. July 2001, roč. 86, čís ... Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa. J. Biol ...
This effect can be seen in the thrombin clotting time (TCT) test, which is prolonged in a person that has active fibrinolysis. ... Plasmin activity is also reduced by thrombin-activatable fibrinolysis inhibitor (TAFI), which modifies fibrin to make it more ... These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and thus slow down clot formation by ...
Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.[20] ...
E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. ... Thrombin is sold under the brand name Fibrimex for use as a binding agent for meat. The thrombin in Fibrimex derives from ... Thrombin interacts with thrombomodulin. As part of its activity in the coagulation cascade, thrombin also promotes platelet ... Due to its high proteolytic specificity, thrombin is a valuable biochemical tool. The thrombin cleavage site (Leu-Val-Pro-Arg- ...
Simulations of the effect of hirudin indicate that factor V is predominantly activated by thrombin and not by factor Xa. The ... A simulation model for the production of thrombin in plasma is presented. Values of the reaction rate constants as determined ... The dependence of this threshold value on different negative feedback reactions, e.g. the inactivation of thrombin and factor ... SBML L2V4 representation of Willems1991 - Simulating thrombin generation. 55.36 KB. Preview , Download. ...
A list of US medications equivalent to Thrombin Sawai is available on the Drugs.com website. ... Thrombin Sawai is a medicine available in a number of countries worldwide. ... Thrombin Sawai may be available in the countries listed below.. Ingredient matches for Thrombin Sawai. Thrombin. Thrombin is ...
Thrombin also has two exosites (1 and 2). Thrombin is a little different from other serine proteases as exosite 1 is anion- ... Thrombin is in the serine protease family. It has 3 binding domains in which thrombin-inhibition drugs bind to. Those proteases ... But heparin can also form a bridge between thrombin and fibrin which binds to exosite 1 which protects the thrombin from ... DTIs arent dependent to cofactors like antithrombin to inhibit thrombin so they can both inhibit free/soluble thrombin as well ...
... stephen goodwin goodwin at BINAH.CC.BRANDEIS.EDU Thu Oct 10 06:42:16 EST 1996 *Previous message: Looking for ... Hi folks Does anyone know of any bead technology that exists that allows efficient removal of thrombin protease after cleavage ...
Home : For health professionals : Refer a patient : Laboratory Services : Test Table : THROMBIN TIME ... Heparin, Direct Thrombin Inhibitors (Lepirudin, Argatroban, Dabigatran, etc.), Fibrin/fibrinogen degradation products may cause ... prolongation of the Thrombin Time. Other interferences include: Hemoglobin (,500 mg/dL), Triglycerides (1,000 mg/dL), Bilirubin ...
... Ding Ming ming at mbcrr.harvard.edu Fri Mar 24 12:35:13 EST 1995 *Previous message: MW of IgG? ... I would appreciate if you can tell me who produce the thrombin antibodies and what their telephone numbers. Thanks in advance. ...
THROMBIN HEAVY CHAINTHROMBIN LIGHT CHAINTHROMBIN PEPTIDEAcetate IonEthyl [(2z)-2-(Carbamimidoylimino)-6-Hydroxy-1,3- ...
Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium.,medicine, ... Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium. ...
Thrombin inhibitor may refer to: Direct thrombin inhibitor Indirect thrombin inhibitor, such as warfarin This disambiguation ... page lists articles associated with the title Thrombin inhibitor. If an internal link led you here, you may wish to change the ...
A "high-affinity" thrombin receptor (PAR1 in human, PAR3 in mouse) is necessary for responses to low concentrations of thrombin ... LDPR/S binds thrombins active center, and the "hirudin-like" sequence DKYEPF binds thrombins fibrinogen-binding exosite (4, ... Human PAR1, PAR3, and PAR4 can be activated by thrombin, and sensing thrombin is likely, at least in part, their role in vivo ( ... 2). PAR1, PAR3, and PAR4 are thrombin receptors (2, 3, 31-33). PAR1 and human PAR3 respond to thrombin at subnanomolar ...
HIRUDINTHROMBIN HEAVY CHAINTHROMBIN LIGHT CHAIN(2s)-1-[cyclohexylamino)acetyl-n-{4-[amino(imino)methyl]benzyl}pyrrolidine-2-carboxamide(S)-N-(4-Carbamimidoylbenzyl)-1-(2-(Cyclohexylamino)ethanoyl)pyrrolidine-2-Carboxamide
Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors.. Nar, H., ... Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to ... current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin ... current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin ...
Thrombin (Topical)). Includes indications, proper use, special instructions, precautions, and possible side effects. ... Thrombin-JMI Epistaxis Kit, Thrombin-JMI Pump Spray Kit, Thrombin-JMI Syringe Spray Kit ... Generic Name: Thrombin (Topical) (THROM bin, TOP i kal). Brand Name: Evithrom, Recothrom, Recothrom Spray Kit, Thrombi-Gel, ... If you have an allergy to thrombin or any other part of Recothrom (thrombin (topical)). ...
... , Topical Thrombin, Topical Thrombin in Gelatin, Floseal. ... Thrombin Hemostatic. Aka: Thrombin Hemostatic, Topical Thrombin, Topical Thrombin in Gelatin, Floseal ...
Kinetic analyses of thrombin activities are routinely used to monitor changes in thrombin reactivity. Computer modeling of ... THROMBIN RESEARCH PROJECT. My main interest of research, which has been funded by Research Corporation and the NIH, involves ... and the production of rabbit antibody fragments recognizing thrombin. ... determining structural features of the bovine clotting enzyme thrombin which control its reactivity with other clotting factors ...
Asp-189 of thrombin and d-Tyr of 8-5 are shown as stick models. Water 38 is represented as a blue ball. The thrombin surface is ... With the exception of the 149-loop (chymotrypsinogen numbering of thrombin), the main chain of the thrombin molecule was fully ... values measured with human thrombin. Like many of the known small-molecule thrombin inhibitors directed against the active site ... Thrombin inhibitors identified by computer-assisted multiparameter design. Daniel Riester, Frank Wirsching, Gabriela Salinas, ...
Thrombin light chain. L. 36. Homo sapiens. Mutation(s): 0 Gene Names: F2. EC: 3.4.21.5. ... Thrombin heavy chain. H. 259. Homo sapiens. Mutation(s): 0 Gene Names: F2. EC: 3.4.21.5. ... Exploring thrombin S3 pocket. Brandt, T., Baum, B., Hangauer, D., Heine, A., Klebe, G.. To be published. ...
thrombin time synonyms, thrombin time pronunciation, thrombin time translation, English dictionary definition of thrombin time ... thrombin time. Translations. English: throm·bin timen. tiempo de trombina, espacio de tiempo necesario para que se forme un ... Diluted thrombin time (dTT): The thrombin time test (TT) measures the time to clot formation in a patient sample following ... Thrombin time - definition of thrombin time by The Free Dictionary https://www.thefreedictionary.com/thrombin+time ...
The reference range for the thrombin time is usually less than 20 seconds (ie, 15-19 seconds), but this depends on the test kit ... Thrombin time is a screening coagulation test designed to assess fibrin formation from fibrinogen in plasma. ... encoded search term (Thrombin Time) and Thrombin Time What to Read Next on Medscape. Related Conditions and Diseases. * ... Thrombin time is a screening coagulation test designed to assess fibrin formation from fibrinogen in plasma. Thrombin time is ...
Baseline Thrombin Time (LIS code: TT; CPT code: 85670) MUST be performed prior to this test. This test should only be performed ... if the baseline thrombin time is higher than the normal range limit and presence of heparin is suspected. Requests for ...
Direct thrombin inhibitor. Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying ... Thrombin demonstrates a high level of allosteric regulation.[2] Allosterism in thrombin is regulated by the exosites 1 and 2 ... This SbO4L shows allosteric inhibition of thrombin for fibrinogen, while providing a competitive inhibition of thrombin ... Di Nisio M, Middeldorp S, Büller H (2005). "Direct thrombin inhibitors". N Engl J Med. 353 (10): 1028-40. doi:10.1056/ ...
Thrombin - gr. thrombos, Thrombase. Klinisches W rterbuch von Otto Dornbl th. Definition und Bedeutung im historischen Lexikon ... Thrombin, Thrombase. Thrombin gr. thrombos Klumpen = Thrombase Fibrinferment, wodurch der l sliche Bluteiwei stoff Fibrinogen ...
a zip file of the full study records in XML for all studies in the search results table (max 10000 ...
The adsorption and the redox behaviour of thrombin-binding aptamer (TBA) and extended TBA (eTBA) were studied using atomic ... Activation of thrombin is crucial in physiological and pathological coagulation. Various rare diseases involving thrombin have ... Thrombin-Binding Aptamer Quadruplex Formation: AFM and Voltammetric Characterization,. Journal of Nucleic Acids,. vol. 2010. , ... Thrombin is a serine protease and a coagulation protein in the blood stream that has many effects in the coagulation mechanism ...
Evithrom [DSC]; Recothrom; Recothrom Spray Kit; Thrombi-Gel; Thrombi-Pad; Thrombin-JMI; Thrombin-JMI Epistaxis Kit; Thrombin- ...
A variety of human thrombin and recombinant thrombin (ie. thrombin alfa) products are available as alternatives to using bovine ... Thrombin requires no intermediate physiological agent for its action. It clots the fibrinogen of the blood directly. Failure to ... Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis [FDA Label]. This thrombosis may result from ... Medical thrombin is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is ...
Read the side effects of Thrombin Topical Bovine Origin as described in the medical literature. In case of any doubt consult ... Side effect(s) of Thrombin Topical Bovine Origin Read the side effects of Thrombin Topical Bovine Origin as described in the ... Thrombin Topical Bovine Origin - Information. Thrombin Topical Bovine Origin is hematologic agent, prescribed for hemostasis ...
The reaction of thrombin was perturbed by addition of hydroxylamine or a co … ... The mechanism of stimulation of platelets by thrombin and other proteases was studied by following kinetics of secretion of ... Platelet stimulation by thrombin and other proteases Biochemistry. 1975 Mar 25;14(6):1308-14. doi: 10.1021/bi00677a032. ... The reaction of thrombin was perturbed by addition of hydroxylamine or a competitive inhibitor and by variation of pH and it ...
  • In the blood coagulation pathway, thrombin acts to convert factor XI to XIa, VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa. (wikipedia.org)
  • Also known as coagulation factor II, thrombin is a serine protease that plays a physiological role in regulating hemostasis and maintaining blood coagulation. (drugbank.ca)
  • In addition to its central role in blood coagulation, it has become increasingly apparent that thrombin and thrombin receptors are involved in many other physiological processes and can contribute to a variety of disease states such as tumor progression and metastasis, inflammation, neurological disorders and cardiovascular complications. (powells.com)
  • It has become increasingly evident in recent years that, apart from the key role that thrombin plays in the blood coagulation cascade, thrombin also elicits cellular actions via the activation of proteinase-activated receptors, which are present in many cell types. (powells.com)
  • No. 25), researchers zeroed in on thrombin, a vitamin K-dependent enzyme key to blood coagulation. (scienceblog.com)
  • Thrombin plays an important role in the blood coagulation cascade and it stimulates the process of platelet aggregation. (rsc.org)
  • Activated platelets participate in thrombin generation through exposure of membrane receptors for blood coagulation proteins, through release of coagulation factors stored in their α-granules, 1 and through formation of a procoagulant surface by rearrangement of their membrane phospholipids to expose negatively charged phosphatidylserine. (ahajournals.org)
  • Thrombin-activatable fibrinolysis inhibitor (TAFI), which is identical to the previously identified proteins procarboxypeptidase B, R, and U, forms a link between blood coagulation and fibrinolysis. (eurekaselect.com)
  • Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. (wikipedia.org)
  • Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). (wikipedia.org)
  • The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36,000 Da. (wikipedia.org)
  • As is the case for all serine proteases, prothrombin is converted to active thrombin by proteolysis of an internal peptide bond, exposing a new N-terminal Ile-NH3. (wikipedia.org)
  • The thrombin (prothrombin) gene is located on the eleventh chromosome (11p11-q12). (wikipedia.org)
  • This polymer had effect on the normal coagulation time by the activated partial thromboplastin time (APTT) and thrombin time (TT) tests using human plasma, except for prothrombin time (TP) test. (thefreedictionary.com)
  • 8) Other indicators for laboratory monitoring of DTI are Activated clotting time (ACT), Ecarin clotting time(ECT), Prothrombin -induced clotting time (PiCT),Diluted thrombin time (Dtt). (thefreedictionary.com)
  • Thrombin time is performed as the next step in the evaluation of abnormally prolonged activated partial thromboplastin time (aPTT) or prothrombin time (PT). (medscape.com)
  • Once converted from prothrombin, thrombin converts fibrinogen to fibrin, which, in combination with platelets from the blood, forms a clot. (drugbank.ca)
  • Medical thrombin is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is activated by tissue thromboplastin in the presence of calcium chloride. (drugbank.ca)
  • Accompanying CNS injury and other cerebral vascular damages, prothrombin activation and leakage of active thrombin into CNS parenchyma has been documented. (ingentaconnect.com)
  • The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin. (abcam.com)
  • The primary goal of this investigation is to determine the ability of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to improve thrombin generation in neonatal plasma after CPB. (clinicaltrials.gov)
  • 1,2 ⇓ Subsequently, a number of investigators demonstrated that the rate of clotting and prothrombin conversion to thrombin was decreased in platelet-poor plasma and increased as a function of platelet number. (ahajournals.org)
  • In Paper I thrombin generation was measured in the absence of thrombomodulin in patients with thrombophilia (factor V Leiden, n=98 and prothrombin G20210A mutation, n=15) and in an equal number of age- and gendermatched controls. (diva-portal.org)
  • Bovine Thrombin is a clotting enzyme that is a serine protease which cleaves Arginine-Glycine bonds in fibrinogen to give clots of fibrin & fibrinpeptide A and B. Bovine Thrombin is derived from bovine prothrombin which is isolated from bovine plasma. (leebio.com)
  • Bovine prothrombin is treated with bovine lung thromboplastin to yield Bovine Thrombin and is also used to remove GST tags from proteins in purification process. (leebio.com)
  • Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. (wikipedia.org)
  • Thrombin is also inactivated by antithrombin, a serine protease inhibitor. (wikipedia.org)
  • Factor Xa with factor V as a cofactor leads to cleavage of the Gla and two Kringle domains (forming together a fragment called fragment 1.2) and leave thrombin, consisting solely of the serine protease domain. (wikipedia.org)
  • They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. (wikipedia.org)
  • As the name indicates the cascade is a multi-step procedure where the main product thrombin is made by activating various proenzymes (mainly serine proteases) in each step of the cascade. (wikipedia.org)
  • Thrombin is in the serine protease family. (wikipedia.org)
  • Thrombin is a serine protease and a coagulation protein in the blood stream that has many effects in the coagulation mechanism. (hindawi.com)
  • Thrombin is well known in its function as the ultimate serine protease in the coagulation cascade. (ingentaconnect.com)
  • Targeting thrombin and other serine proteinases 2.7.2. (powells.com)
  • Thrombin-like snake venom serine protease. (uniprot.org)
  • Human thrombin, a highly specific serine protease, is a biomarker that plays an important role in the coagulation cascade. (mdpi.com)
  • Thrombin, a serine protease, plays a central role in hemostasis by converting soluble plasma fibrinogen into an insoluble fibrin clot and by promoting platelet aggregation. (anaspec.com)
  • Thrombin is the key serine protease of the coagulation cascade and a potent trigger of protease-activated receptor 1 (PAR1)-mediated platelet aggregation. (sigmaaldrich.com)
  • Thrombin is a coagulation protein and a serine protease (EC 3.4.21.5) that catalyzes many coagulation-related reactions. (prospecbio.com)
  • Thrombin is a coagulation protein that has many effects in the coagulation cascade and is a serine protease that converts fibrinogen into fibrin. (leebio.com)
  • Thrombin bound to thrombomodulin activates protein C, an inhibitor of the coagulation cascade. (wikipedia.org)
  • The activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin, an integral membrane protein expressed by endothelial cells. (wikipedia.org)
  • Hi folks Does anyone know of any bead technology that exists that allows efficient removal of thrombin protease after cleavage of a fusion protein? (bio.net)
  • The coagulation protease thrombin (EC 3.4.21.5 ) activates platelets and regulates the behavior of other cells by means of G protein-coupled protease-activated receptors (PARs). (pnas.org)
  • Thrombin signaling is mediated at least in part by a family of G protein-coupled protease-activated receptors (PARs), for which PAR1 is the prototype ( 2 , 3 ). (pnas.org)
  • Thrombin (large sphere) recognizes the amino-terminal exodomain of the G protein-coupled thrombin receptor PAR1. (pnas.org)
  • A considerable number of thrombin inhibitors developed so far suffer from poor selectivity, inherent toxicity, high-plasma protein binding, poor metabolic stability, rapid elimination from the blood, low anticoagulant activity, or poor oral bioavailability, to name but a few problems. (pnas.org)
  • One of the most preeminent examples of the in vitro selection of DNA oligonucleotides for targeting a specific protein is the thrombin-binding aptamer (TBA), Scheme 2 . (hindawi.com)
  • Thrombin interaction with protein C 1.7. (powells.com)
  • Thrombin-activated protein C: integrated to regulate vascular physiology 4.1. (powells.com)
  • The protein C pathway is localized to the endothelial cell surface and limits thrombin generation through negative feedback 4.2. (powells.com)
  • Thrombin is a protein that is produced naturally in the body. (mayoclinic.org)
  • Recothrom® is a man-made protein produced to replicate the naturally occurring thrombin in the body. (mayoclinic.org)
  • EVITHROM* is a manufactured human plasma-derived alternative to the use of bovine protein-based thrombin, which is currently used to control bleeding in approximately one million surgical procedures each year in the United States. (fiercebiotech.com)
  • FDA approved Evithrom (human thrombin), a blood-clotting protein used to help control bleeding during surgery. (emaxhealth.com)
  • An unusual enzyme, thrombin performs distinct and even opposing functions, acting as a pro-coagulant, pro-thrombotic but also as an anti-coagulant factor depending on which target protein - fibrinogen, PAR1 or protein C - becomes activated in the blood. (scienceblog.com)
  • Researchers studied thrombin to decipher the structure-function code that enables this protein to do so many different things. (scienceblog.com)
  • Using protein engineering, researchers produced mutations in the enzyme's amino acid sequence, carefully taking out pieces and replacing them, a few at a time, to find the exact locations that influence the function of thrombin. (scienceblog.com)
  • They engineered thrombin to promote activity toward protein C - the anticoagulant target protein - and minimize activity toward fibrinogen and PAR1 - the procoagulant and prothrombotic targets. (scienceblog.com)
  • Furthermore, we generated a new mutant with exclusive prothrombotic activity, thereby demonstrating that the individual functions of thrombin can be dissociated by replacing a single amino acid in the protein. (scienceblog.com)
  • We offer PAR1/Thrombin Receptor Peptides and PAR1/Thrombin Receptor Proteins for use in common research applications: ELISA, Protein Array, Western Blot. (novusbio.com)
  • Each PAR1/Thrombin Receptor Peptide and PAR1/Thrombin Receptor Protein is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
  • Thrombomodulin (TM), a membrane proteoglycan on endothelial cells, binds thrombin in a 1:1 complex, accelerates the protein C activation by thrombin, promotes the thrombin inactivation by antithrombin III and inhibits the procoagulant properties of thrombin. (tudelft.nl)
  • however, suppression of protein kinase C activity did not reverse the thrombin effect. (ahajournals.org)
  • Specifically, study investigators expect to determine whether bivalirudin, a direct inhibitor of the clotting protein thrombin, is better than unfractionated heparin, an indirect thrombin inhibitor, in patients who have also been treated with high-dose clopidogrel. (bio-medicine.org)
  • As a result of its high proteolytic specificity, thrombin has become an important biochemical protein. (prospecbio.com)
  • The thrombin cleavage site (Leu-Val-Pro-Arg-Gly-Ser) is widely used in linker regions of recombinant fusion protein constructs. (prospecbio.com)
  • After the purification of the fusion protein, thrombin is used to cleave between the Arginine and Glycine residues of the cleavage site, efficiently removing the purification tag from the protein of interest with a high degree of specificity. (prospecbio.com)
  • Lyophilized Thrombin although stable at room temperature for 3 weeks, should be stored desiccated below -18°C. Upon reconstitution Thrmbin should be stored at 4°C between 2-7 days and for future use below -18°C. For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA). (prospecbio.com)
  • Bovine Thrombin has an essential role in the clotting process and has been well characterized where it converts fibrinogen, a soluble plasma glycoprotein, to an insoluble protein gel called fibrin, the essential component of the blood clot. (leebio.com)
  • I found out that thrombin has two cleavage sites in the protein sequence whereas trypsin had more than 20 cleavage sites. (biology-online.org)
  • In this regard, thrombin not only activates endothelial cells and induces leukocyte infiltration and edema but also activates astrocytes, and particularly microglia, as recently demonstrated, to propagate the focal inflammation and produce potential neurotoxic effects. (ingentaconnect.com)
  • alpha-Thrombin, bradykinin, and histamine are endogenous mediators that increase endothelial permeability. (nih.gov)
  • This endothelial activation could lead to a secretion of many proinflammatory cytokines and growth factors, such as thrombin. (biomedsearch.com)
  • The primary objective is to determine the onset-, maintenance-, and offset-effects of vorapaxar on thrombin generation kinetics (clotting time, thrombin generation, platelet-fibrin clot strength, and clot lysis) and endothelial function in antiplatelet naïve patients and patients on mono-and dual-antiplatelet therapy. (inova.org)
  • Thrombin and the atrial natriuretic peptide (ANP) possess a number of functionally antagonistic properties in vascular endothelial cells. (ahajournals.org)
  • Thrombin treatment effected a dose- and time-dependent reduction in ANP receptor activity (maximal 70% to 80% inhibition) in cultured bovine aortic endothelial cells. (ahajournals.org)
  • Pretreatment of endothelial cells with cycloheximide did not completely prevent the thrombin-dependent inhibition, and thrombin did not effect a reduction in type C receptor mRNA levels, findings that argue for a postsynthetic inhibitory locus. (ahajournals.org)
  • Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells. (sigmaaldrich.com)
  • Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. (sigmaaldrich.com)
  • Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. (sigmaaldrich.com)
  • Our study provides a unique resource of phosphoproteins and phosphorylation sites that may generate novel insights into an intimate understanding of thrombin-mediated PAR signaling and the development of improved PAR1 antagonists that affect platelet but not endothelial cell function. (sigmaaldrich.com)
  • Thrombin mediates changes in endothelial barrier function and increases endothelial permeability. (ahajournals.org)
  • A feature of thrombin-enhanced endothelial hyperpermeability is contraction of endothelial cells (ECs), accompanied by formation of focal adhesions (FAs). (ahajournals.org)
  • Depletion of GIT1 with antisense GIT1 oligonucleotides had no effect on basal cell morphology, but increased cell rounding and contraction of HUVECs, increased FA formation, and increased FAK tyrosine phosphorylation in response to thrombin, concomitant with increased endothelial hyperpermeability. (ahajournals.org)
  • 2,3 Thrombin contraction is accompanied by formation of small gaps between cells and disturbed barrier function of the endothelial monolayer, 4,5 the major cause of vascular leakage under inflammatory conditions. (ahajournals.org)
  • Because the permeability-enhancing effects of thrombin are reversible and GIT1 regulates assembly of FAs, we hypothesized that GIT1 mediates recovery from thrombin-induced endothelial barrier injury. (ahajournals.org)
  • We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. (mdpi.com)
  • Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. (mdpi.com)
  • In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. (mdpi.com)
  • Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence. (mdpi.com)
  • My main interest of research, which has been funded by Research Corporation and the NIH, involves determining structural features of the bovine clotting enzyme thrombin which control its reactivity with other clotting factors in the blood. (csbsju.edu)
  • This work involves purification and characterization of many proteins from bovine blood and lungs, synthesis of peptides (by manual solid state techniques) and characterization (by chemical and chromatographic techniques), and the production of rabbit antibody fragments recognizing thrombin. (csbsju.edu)
  • Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis Label . (drugbank.ca)
  • This thrombosis may result from the development of antibodies against bovine thrombin Label . (drugbank.ca)
  • Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product Label . (drugbank.ca)
  • Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis Label . (drugbank.ca)
  • thrombin alfa) products are available as alternatives to using bovine thrombin. (drugbank.ca)
  • Bovine thrombin is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (like suture, ligature, or cautery) is ineffective or impractical Label . (drugbank.ca)
  • Additionally, topical bovine thrombin can also be used in combination with an absorbable gelatin sponge, USP Label . (drugbank.ca)
  • Little has been reported about the systemic pharmacodynamics and pharmacokinetics of bovine thrombin preparations 2 , but it is expected that bovine thrombin elicits similar activities as endogenous thrombin. (drugbank.ca)
  • Read the side effects of Thrombin Topical Bovine Origin as described in the medical literature. (medindia.net)
  • Omrix's Thrombin stand-alone, which is derived from human plasma, is designed to provide effective hemostasis (control of bleeding) without the risk of adverse reactions associated with the use of bovine-sourced hemostats. (fdanews.com)
  • Assay principle HEMOCLOT T.T. is an clotting assay developed for the determination of the Thrombin Time induced by bovine thrombin (Thrombin Time, T.T.), in presence of calcium, on human citrated plasma, and exploration of the anti-thrombin activities. (webwire.com)
  • Exposure to bovine-derived thrombin has been shown to produce an immunogenic response in some patients. (fiercebiotech.com)
  • In patients who develop antibodies to bovine-derived thrombin there is an increased risk for complications including severe bleeding, thrombosis and anaphylactic shock. (fiercebiotech.com)
  • In addition, patients who develop antibodies to bovine-derived thrombin preparations are at a significantly higher risk of immunogenic response when re-exposed to these products. (fiercebiotech.com)
  • Based on the product type, the thrombin market has been segmented into bovine thrombin, human thrombin and recombinant thrombin. (bccresearch.com)
  • This is a Phase 3 multiple site, randomized, double-blind, controlled trial designed to evaluate the comparative efficacy and safety of rhThrombin and bovine thrombin in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access. (knowcancer.com)
  • After establishing eligibility, subjects will be randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). (knowcancer.com)
  • During a surgical procedure, study participants will be treated with blinded study drug (rhThrombin or bovine thrombin) in combination with an absorbable gelatin sponge at appropriate bleeding evaluation site(s) and time to hemostasis (TTH) will be assessed for up to 10 minutes. (knowcancer.com)
  • Lee Biosolutions produces and supplies high purity bovine Thrombin for medical research of proteolytic enzymes and manufacturing of defibrinating human plasma and serum free media component. (leebio.com)
  • Lee Biosolutions High Specific Activity Bovine Thrombin product is used to cleave r-fusion proteins containing a thrombin site for removal of affinity tags as well as certain diagnostic pharmaceutical applications. (leebio.com)
  • Bovine Thrombin used as a reagent, which has proven useful in the laboratory evaluation of many fibrinogens. (leebio.com)
  • Bovine Thrombin is a multi-functional proteolytic enzyme which acts both specifically and non-specifically with several proteins, cells, surfaces, and other molecules. (leebio.com)
  • The SensoLyte 520 Thrombin Assay Kit is optimized for detecting thrombin activity. (anaspec.com)
  • 130 of 139 (94%) of the individual normal plasmas triggered thrombin generation with an approx. (uni-marburg.de)
  • Of the N=139 individual normal plasmas that were supplemented with up to 20 mg/l of gentamicin, 6 of 139 (4%) were resistant towards gentamicin-triggered thrombin generation. (uni-marburg.de)
  • Abstract -Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described fibrinolysis inhibitor that circulates in plasma as a procarboxypeptidase and is converted into an active form during coagulation. (ahajournals.org)
  • Thrombin also activates factor XIII that stabilizes the fibrin complex and therefore the clot and it stimulates platelets, which help with the coagulation. (wikipedia.org)
  • Perhaps the best-studied example of such a process is activation of platelets by the coagulation protease thrombin (EC 3.4.21.5 ). (pnas.org)
  • Because platelets and thrombin are important in myocardial infarction and other thrombotic processes, understanding how thrombin activates platelets has long been an important goal ( 1 ). (pnas.org)
  • How does thrombin talk to platelets? (pnas.org)
  • The mechanism of stimulation of platelets by thrombin and other proteases was studied by following kinetics of secretion of Ca2+ or ATP. (nih.gov)
  • a calculated inhibition constant was in agreement with the value for a synthetic substrate, suggesting that the interaction of thrombin with platelets is analogous to reaction with substrates. (nih.gov)
  • Platelet-rich plasma (PRP) samples were preincubated with buffer or CLA and subsequently platelets were activated by the protease-activated receptor 1 (PAR-1) activator, thrombin receptor activating peptide (TRAP). (hindawi.com)
  • This review examines the evidence that platelets play a major role in localizing and controlling the burst of thrombin generation leading to fibrin clot formation. (ahajournals.org)
  • When it was found that phosphatidylserine containing lipid extracts could be substituted for platelets in clotting assays, this suggested the possibility that changes in platelet lipid composition were necessary and sufficient to account for platelet surface thrombin generation. (ahajournals.org)
  • Also, we review data suggesting that platelets from different individuals differ in their capacity to generate thrombin, whereas platelets from a single subject support thrombin generation in a reproducible manner. (ahajournals.org)
  • The initial studies of clotting assays relied on patient platelets in the platelet-rich plasma as the surface for thrombin generation. (ahajournals.org)
  • 14 Because there was an obvious correlation between the observation that activated platelets express phosphatidylserine and the observation that phosphatidylserine in purified lipids is required for thrombin generation, it was concluded by many that phosphatidylserine exposure provided the primary mechanism for regulating coagulation reactions and thrombin generation. (ahajournals.org)
  • 1 2 Thus, antiplatelet agents may contribute in vivo to an inhibition of coagulation by decreasing thrombin generation at the surface of platelets. (ahajournals.org)
  • 8 These compounds were recently shown to significantly inhibit the in vitro thrombin generation triggered by low concentrations of tissue factor in the presence of platelets by inhibiting platelet ADP receptors. (ahajournals.org)
  • 10 ADP participates in the binding of fibrinogen to platelets stimulated by thrombin 11 and is involved in stabilizing the platelet aggregates induced by thrombin stimulation. (ahajournals.org)
  • The molecule thrombin plays a key role in the bowel inflammation driven by overactive platelets. (medicalxpress.com)
  • Thrombin signalling initiates inflammatory events directly and through activation of platelets. (ahajournals.org)
  • Diluted thrombin time (dTT): The thrombin time test (TT) measures the time to clot formation in a patient sample following addition of excess thrombin. (thefreedictionary.com)
  • Clot retraction was detected by observing clot morphology up to 1 hour, phosphatidylserine- (PS-) expression was studied by flow cytometry, and thrombin generation was measured by a fluorimetric assay. (hindawi.com)
  • CLA preincubation inhibited clot retraction, PS-expression, and thrombin formation. (hindawi.com)
  • Our results show that CLA pretreatment may be a useful tool to investigate platelet activation mechanisms that contribute to clot formation and thrombin generation. (hindawi.com)
  • Thrombin converts soluble fibrinogen into a fibrin clot. (eurekaselect.com)
  • Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. (wikipedia.org)
  • A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric and multi-mechanism inhibitors might lead the way to a safer anticoagulant. (wikipedia.org)
  • Given this broad action of thrombin it stands as a good drug target for anticoagulant drugs such as heparin, warfarin and DTIs and antiplatelet drugs like aspirin. (wikipedia.org)
  • WE: a prototypic anticoagulant/antithrombotic thrombin 1.10. (powells.com)
  • Antithrombotic/Anticoagulant Drugs: Techs and Global Markets (PHM119B) analyzes the market size of anticoagulants by revenue at manufacturers' sales levels, including low molecular weight heparins and oral anticoagulants, as well as breakdowns of antiplatelets and thrombin inhibitors. (bccresearch.com)
  • In 2000, we engineered a thrombin mutant with potent anticoagulant properties both in vitro and in vivo and we are moving this mutant to a phase I trial," said Di Cera. (scienceblog.com)
  • In a double-blind, multicenter trial, we randomly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran (24 mg) or placebo, taken twice daily, for 18 months without monitoring of coagulation. (unboundmedicine.com)
  • Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to antithrombotic therapy could result in potent anticoagulants with improved pharmacological properties. (rcsb.org)
  • This SbO4L shows allosteric inhibition of thrombin for fibrinogen, while providing a competitive inhibition of thrombin interaction with platelet glycoprotein Ibα (GPIbα), thereby preventing thrombin mediated platelet aggregation. (wikipedia.org)
  • Targeted inhibition of thrombin within the coagulation cascade has been another focus of research in the investigation of novel anticoagulants. (mja.com.au)
  • Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. (diva-portal.org)
  • S. Alban, " Pharmacological Strategies for Inhibition of Thrombin Activity", Current Pharmaceutical Design (2008) 14: 1152. (eurekaselect.com)
  • Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. (mdpi.com)
  • The synthetic peptide SFLLRN, which mimics the first six amino acids of the new amino terminus unmasked by receptor cleavage, functions as an agonist for PAR1 and activates the receptor independently of thrombin and proteolysis ( 2 , 6 , 7 ). (pnas.org)
  • This interaction utilizes sites both amino-terminal (P1-P4, small sphere) and carboxyl-terminal (P9′-P14′, small oval) to the thrombin cleavage site. (pnas.org)
  • This peptide forms the N-terminal sequence left after thrombin cleavage of the receptor's amino-terminal exodomain thereby activating the thrombin receptor PAR1. (anaspec.com)
  • 1 It circulates as a procarboxypeptidase B zymogen, which is converted into an active form, carboxypeptidase U (EC3.4.17.20), or TAFIa, during coagulation 2 after thrombin cleavage. (ahajournals.org)
  • As part of its activity in the coagulation cascade, thrombin also promotes platelet activation and aggregation via activation of protease-activated receptors on the cell membrane of the platelet. (wikipedia.org)
  • An intracellular pool of thrombin receptors refreshes the cell surface with naïve receptors, thereby maintaining thrombin responsiveness. (pnas.org)
  • Recently revealed molecular mechanisms underlying these thrombin effects appear to involve proteolytic activation of two different thrombin-responsive, protease-activated receptors (PARs), PAR1 and PAR4, possibly in concert. (ingentaconnect.com)
  • Thrombin and thrombin receptors are involved in many physiological processes and can contribute to a variety of disease states. (powells.com)
  • Cell type specific expression of thrombin receptors 3.3. (powells.com)
  • In the present study we have assessed the acute inflammatory effect of inhaled thrombin and investigated the possible receptors mediating any effects in mice. (wiley.com)
  • 12 At the intracellular level, ADP has been shown to act synergistically with thrombin to activate PI 3-kinase 13 and phospholipase D. 14 Two ADP receptors involved in ADP-induced platelet responses have been described to date. (ahajournals.org)
  • Thrombin endorses platelet activation, using activation of protease-activated receptors on the platelet. (prospecbio.com)
  • We showed that anti-thrombin nanoparticles can find, capture and inactivate all the active thrombin in the gut, thereby preventing or reducing the small blood vessel damage and clotting that accelerates NEC. (medicalxpress.com)
  • Contrary to crystal structures of active thrombin, hydrogen-deuterium exchange mass spectrometry studies indicate that this N-terminal Ile-NH3 does not become inserted into the β-barrel in the apo form of thrombin. (wikipedia.org)
  • One of the early orally active thrombin inhibitors, ximelagatran, demonstrated promising safety and efficacy compared with enoxaparin for thromboprophylaxis in major orthopaedic surgery but was subsequently abandoned after it was found to cause liver dysfunction in some patients. (mja.com.au)
  • Active thrombin is found in the airways of patients with a variety of inflammatory lung diseases. (wiley.com)
  • Biologically Active Thrombin-Containing Hydrogels Based on Poly(2-hydroxyethyl methacrylate) for Endovascular Occlusion", Polymers in Medicine, 1991, vol. (patentgenius.com)
  • Emerging evidence indicates that thrombin also functions as a potent signaling molecule that regulates physiologic and pathogenic responses alike in a large variety of cell populations and tissues. (ingentaconnect.com)
  • However, whether thrombin contributes to the pathologies of these diseases is unknown, although thrombin is a potent inflammatory mediator in other organ systems. (wiley.com)
  • The investigative therapy essentially works "like a thrombin sponge" that is exponentially more potent than current agents used to inhibit clotting, Dr. Wickline explained. (medicalxpress.com)
  • Thrombin promotes chemotaxis in monocytes, neurite retraction in neuron Thrombin serves as a potent mitogenic agent in fibroblast growth and functions as a serum-free media component for several cell lines. (leebio.com)
  • The dependence of this threshold value on different negative feedback reactions, e.g. the inactivation of thrombin and factor Xa by antithrombin III (+ heparin), is investigated. (ebi.ac.uk)
  • The thrombin time is very sensitive to unfractionated heparin (≥0.05 U/mL) and might be used for detection of accidental heparin contamination of a plasma specimen. (medscape.com)
  • This test should only be performed if the baseline thrombin time is higher than the normal range limit and presence of heparin is suspected. (nationwidechildrens.org)
  • Recent innovations and the emergence of novel thrombin inhibitors have led to the decline of traditional anticoagulants such as heparin and Vitamin K antagonists, as well. (bccresearch.com)
  • Direct thrombin inhibitors, such as dabigatran, might be efficient in the treatment of patients with AD because of their high selectivity for thrombin's activity inhibition while having a safer side effects profile than heparin. (biomedsearch.com)
  • Heparin is a brute-force remedy that shuts down all thrombin functions, including its beneficial anti-coagulant role," said Di Cera. (scienceblog.com)
  • The small leucine-rich proteoglycan biglycan (BGN) is thought to inhibit thrombin activity by activation of heparin cofactor II. (ahajournals.org)
  • Thrombin cleaves the peptide bond between receptor residues Arg-41 and Ser-42. (pnas.org)
  • Although isolated alveolar macrophages appeared to express PAR 1 - and PAR 4 -immunoreactivity, these cells failed to release TNF- α above baseline levels in response to thrombin, trypsin or any of the peptide PAR agonists. (wiley.com)
  • A variety of human thrombin and recombinant thrombin (ie. (drugbank.ca)
  • In the presence of an excess of a fully-glycosylated soluble recombinant human TM mutant (high-M(r) rec-TM), 0.11 nM thrombin inactivated 50% of 4.4nM scu-PA in 45min at 37°C. In the presence of a soluble recombinant TM mutant lacking the glycosaminoglycans (low-M(r) rec-TM), 1.9nM thrombin was needed to inactivate 50% scu-PA, as compared with 4.7nM thrombin in the absence of TM. (tudelft.nl)
  • Recombinant topical thrombin at a concentration of 1,000 IU/1 ml. was incrementally injected in small aliquots of 100 IU into the PSA under gray-scale and intermittent Doppler imaging until the PSA appeared thrombosed as determined by elimination of Doppler signal in the PSA sac. (appliedradiology.com)
  • thrombin antibodies? (bio.net)
  • I would appreciate if you can tell me who produce the thrombin antibodies and what their telephone numbers. (bio.net)
  • Thrombin topical is used to help control minor bleeding and oozing during surgery. (mayoclinic.org)
  • Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of thrombin topical in children. (mayoclinic.org)
  • As a topical hemostatic agent, thrombin has wide application for many surgical treatments. (dovepress.com)
  • During the past 4 months I have conducted several double-blind studies to investigate the efficacy of topical thrombin in the control of bleeding from the puncture sites in dialysis patients. (annals.org)
  • Concentrations of tumour necrosis factor- α (TNF- α ) were elevated in BAL fluid from thrombin-treated mice, and a TNF- α -neutralising antibody inhibited the influx of neutrophils in response to thrombin. (wiley.com)
  • TBA has also been used for development of electrochemical biosensors for the detection of thrombin [ 10 ]. (hindawi.com)
  • The investigation has demonstrated that such a GMR aptasensor has the required sensitivity for the real time, label-free, in situ detection of thrombin and provides kinetic information related to the binding. (mdpi.com)
  • Endogenous and pharmacologic inhibitors of thrombin are therefore of relevance during atheroprogression and for therapeutic intervention. (ahajournals.org)
  • Consequently, the search for new anticoagulants focus on inhibitors of thrombin or FXa. (eurekaselect.com)
  • Chantal Verkleij bestudeerde de rol van Thrombin-activatable fibrinolysis inhibitor - een eiwit dat bloedstolsels beschermt tegen een vroegtijdige afbraak - bij het ontstaan van hart- en vaatziekten, en tijdens de wondgenezing. (uva.nl)
  • Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme that, once activated, attenuates fibrinolysis. (queensu.ca)
  • Pauline F. Marx, " Thrombin-Activatable Fibrinolysis Inhibitor", Current Medicinal Chemistry (2004) 11: 2335. (eurekaselect.com)
  • Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described fibrinolysis inhibitor cloned from human liver. (ahajournals.org)
  • PAR2 is activated by trypsin and by trypsin-like proteases but not by thrombin. (pnas.org)
  • The reaction of thrombin was perturbed by addition of hydroxylamine or a competitive inhibitor and by variation of pH and it was compared with the reactions of other proteases. (nih.gov)
  • The most recent research has focused on agents that operate via the targeted inhibition of specific factors within the coagulation cascade, in particular, the inhibition of proteases such as thrombin or activated factor X (Xa). (mja.com.au)
  • Thrombin (200-2000 U kg −1 intranasally), induced the recruitment of a small, but significant, number of neutrophils into the airways as assessed by differential counts of cells retrieved by bronchoalveolar lavage (BAL). (wiley.com)
  • Finally, the concentration of thrombin could be accurately determined by means of measuring the phosphorescence intensity change value (Δ P ). The limit of detection (LOD) was obtained as low as 15.26 pM with wide linear ranges both from 60 to 2000 pM and from 2 to 900 nM. (rsc.org)
  • For this reason, the authors retrospectively reviewed all cases of arterial PSAs that occurred at non-groin sites treated with percutaneous ultrasound-guided thrombin injection between January 2000 and October 2016 at Mayo Clinic in Rochester, MN to determine the safety and effectiveness of the procedure. (appliedradiology.com)
  • Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting ) by directly inhibiting the enzyme thrombin (factor IIa). (wikipedia.org)
  • Thrombin inhibitors are anticoagulants that inhibit the enzyme thrombin. (bccresearch.com)
  • Trypsin and papain, with specificities for arginyl residues, induced secretion with a time course that was nearly identical with that induced by thrombin when saturating levels of enzyme were used. (nih.gov)
  • I should pick thrombin over trypsin because it is more specific. (biology-online.org)
  • PAR1 is activated when thrombin binds to and cleaves its amino-terminal exodomain to unmask a new receptor amino terminus. (pnas.org)
  • PAR1, PAR3, and PAR4 can all be activated by thrombin. (pnas.org)
  • Thrombin activates PAR1 by binding to and cleaving its amino-terminal exodomain to unmask a new receptor amino terminus ( 2 ). (pnas.org)
  • Our PAR1/Thrombin Receptor Peptides and PAR1/Thrombin Receptor Proteins can be used in a variety of model species: Human. (novusbio.com)
  • Those sites were localized on proteins that are novel to thrombin signaling, but also on well-known players such as PAR1, Rho-associated kinase 2, phospholipase C, and proteins related to actin cytoskeleton, cell-cell junctions, and Weibel-Palade body release. (sigmaaldrich.com)
  • These data also show, for the first time, that histamine and alpha-thrombin increased permeability by calcium-dependent intracellular pathways, but bradykinin operates through a calcium-independent mechanism. (nih.gov)
  • Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. (diva-portal.org)
  • Conclusion: Proliferative vitreoretinopathy (PVR) is associated with increased intravitreal thrombin activity that activates profibrotic and proinflammatory pathways in RPE cells. (eur.nl)
  • 6 More recently, clinical trials have been performed on a new oral thrombin inhibitor, dabigatran etexilate. (mja.com.au)
  • We examined the effect of co-treatment with dabigatran etexilate, a direct thrombin inhibitor, and cisplatin using the murine ID8 ovarian cancer model. (sigmaaldrich.com)
  • These results demonstrate that co-treatment with dabigatran etexilate significantly augments the anti-tumor activity of cisplatin in ovarian tumor progression by alleviating the immunosuppressive microenvironment, suggesting that thrombin may be a potential therapeutic target for treatment of ovarian cancer. (sigmaaldrich.com)
  • Thrombin receptor signaling to heterotrimeric G-proteins 3.3.3. (powells.com)
  • Because a growing body of data suggest that platelet-binding proteins provide much of the specificity for platelet thrombin generation, we review in this report data suggesting that changes in lipid composition are necessary but not sufficient to account for platelet surface regulation of thrombin generation. (ahajournals.org)
  • Individual differences in platelet thrombin generation might be accounted for by differences in platelet-binding proteins. (ahajournals.org)
  • The Mouse Thrombin-antithrombin (TAT) complexes ELISA Kit (Colorimetric) measures mouse Thrombin-antithrombin (TAT) complexes in plasma, cell culture. (fishersci.com)
  • Methods and Results -Human thromboplastin was injected intravenously into wild-type or P2Y 1 -deficient mice, and the effects on platelet count and mortality were determined and plasma thrombin-antithrombin III (TAT) complexes were quantified. (ahajournals.org)
  • Die glyco-anticoagulants act partially (GAGs) or exclusively (oligosaccharides) by catalysing antithrombin, whereas the xenobiotic anticoagulants are direct inhibitors of either thrombin or FXa. (eurekaselect.com)
  • The phase III RENOVATE trial, published in the latest edition of The Lancet, has revealed safety and tolerability data concerning Boehringer Ingelheim's (BI) oral thrombin inhibitor, dabigatran. (pmlive.com)
  • Thrombin inhibitor may refer to: Direct thrombin inhibitor Indirect thrombin inhibitor, such as warfarin This disambiguation page lists articles associated with the title Thrombin inhibitor. (wikipedia.org)
  • In this study, we examined the capacity of the clinically available direct thrombin inhibitor dabigatran to inhibit thrombin activity in vitreous fluids. (eur.nl)
  • In addition, dabigatran that reached the vitreous after repeated oral intake did inhibit thrombin activity in the in vitro activity assay. (eur.nl)
  • The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak). (diva-portal.org)
  • Freeze-dried human thrombin (1.5NIH units/mL) with calcium. (bio-medicine.org)
  • Thrombin-like enzyme that shows clotting activity upon human plasma. (uniprot.org)
  • The influence of gentamicin on the generation of thrombin, the most important enzyme of human coagulation, was analysed. (uni-marburg.de)
  • Evithrom is the first human thrombin approved since 1954 and is the only product currently licensed. (emaxhealth.com)
  • Surgeons will now be able to choose between human thrombin and thrombin derived from cattle plasma. (emaxhealth.com)
  • The in vitro effects of thrombomodulin on the inactivation of single chain urokinase-type plasminogen activator (scu-PA) by thrombin were investigated by incubating scu-PA with varying concentrations of human thrombin, in both the absence and presence of soluble rabbit thrombomodulin. (tudelft.nl)
  • The medicines below all contain the following active ingredient(s): human thrombin + calcium chloride. (healthdirect.gov.au)
  • This aptasensor was also able to detect thrombin in the human serum at picomolar levels. (springer.com)
  • The proposed strategy was also successfully applied for thrombin detection in human serum samples and plasma samples with satisfactory recoveries from 96% to 99% and 95% to 104%, respectively. (rsc.org)
  • The FT solution was made up of 2 separate solutions of fibrinogen (fibronectin, factor XIII, plasminogen, and aprotin) and human thrombin. (lww.com)
  • Our customers use Thrombin to defibrinate human plasma, producing serum matrices to be used as controls and standards around the world. (leebio.com)
  • In human umbilical vein ECs (HUVECs), thrombin recruited GIT1 to FAs, where GIT1 colocalized with FAK and vinculin. (ahajournals.org)
  • Human Thrombin although stable at RT for 2-8°C, should be stored desiccated below -18°C. (acris-antibodies.com)
  • In Paper II, thrombin generation at the time of an acute thromboembolic episode was studied as a potential early marker for recurrence during a 7-year follow-up in 115 patients with venous thrombosis upon inclusion. (diva-portal.org)
  • In Paper IV, thrombin generation was measured in the presence and absence of thrombomodulin in 47 patients with portal vein thrombosis, PVT (11 with cirrhotic PVT and 36 with non-cirrhotic PVT), 15 patients with Budd-Chiari syndrome and 24 patients with cirrhosis, as well as 21 healthy controls. (diva-portal.org)
  • It was shown that hypercoagulability, expressed as total and maximum concentration of generated thrombin as well as thrombomodulin resistance [thrombin generation markers measured in the presence]/[thrombin generation markers measured in the absence of thrombomodulin] was pronounced in the groups of patients with cirrhosis, regardless of the presence of splanchnic thrombosis. (diva-portal.org)
  • Antiplatelet agents impairing platelet functions have proved effective in arterial thrombosis, in which high-flow conditions prevail, whereas anticoagulants act essentially by decreasing circulating thrombin concentrations, which are involved in many thrombotic events and particularly in venous thrombosis, in which stasis occurs. (ahajournals.org)
  • This has been demonstrated for anti-GP IIb/IIIa agents, which inhibit stasis-induced venous thrombosis in vivo 3 and thrombin formation in vitro. (ahajournals.org)
  • This is followed by irreversible, thrombin-independent platelet processes leading to secretion, with yield dependent on the equilibrium concentration of the thrombin product. (nih.gov)
  • The sensitivity reported in this first trial study is 0.04 nm/μM for thrombin detection in the concentration range from 0.25 to 1 μM and the limit of detection (LOD) is 0.19 μM. (mdpi.com)
  • The identified lead compounds exhibited thrombin inhibitory constants in the lower nanomolar range. (pnas.org)
  • A prolonged thrombin time indicates a fibrinogen abnormality, impairment of fibrin formation, and/or a thrombin inhibitory effect. (medscape.com)
  • As a consequence of the inhibitory effect on calcium elevation and PS-expression, CLA significantly downregulated thrombin generation in PRP. (hindawi.com)
  • Proteolytic mechanism of thrombin receptor activation 3.3.2. (powells.com)
  • Maximum intracellular calcium in HUVEC was increased by alpha-thrombin (245 +/- 20 nM) and histamine (210 +/- 22 nM), but not by bradykinin (70 +/- 7 nM) as compared to control (69 +/- 10). (nih.gov)
  • There are three types of DTIs, dependent on their interaction with the thrombin molecule. (wikipedia.org)
  • The team found that inhibiting the inflammatory and blood -clotting molecule thrombin with targeted nanotherapy can protect against NEC-like injury in newborn mice. (medicalxpress.com)
  • Our data identified the inflammatory molecule thrombin, which plays a critical role in platelet-activated blood clotting, as a potential new therapeutic target for NEC," said coauthor Samuel Wickline, MD, professor of cardiovascular sciences at Morsani College of Medicine and director of the USF Health Heart Institute. (medicalxpress.com)
  • Potential therapeutic strategies based on appreciation of the current understanding of molecular mechanisms underlying thrombin-induced CNS inflammation are also discussed. (ingentaconnect.com)
  • These effects of thrombin are seen in a variety of physiological as well as pathological phenomena, including vascular development and physiology, tumor progression and metastasis, neuronal functions, inflammation, angiogenesis. (powells.com)
  • Thrombin: to PAR or not to PAR, and the regulation of inflammation 2.1. (powells.com)
  • PAR activation and the inflammation actions of thrombin 2.6. (powells.com)
  • It literally puts trillions of nanoparticles at that damaged (intestinal wall) site to sponge up all the overactive thrombin, which tones down the clotting and inflammation processes promoted by thrombin. (medicalxpress.com)
  • Hypothesis: Genetic deletion of BGN affects thrombin activity, inflammation and atherosclerosis. (ahajournals.org)
  • The present results indicate that BGN plays a previously unappreciated protective role during progression of atherosclerosis by inhibiting thrombin activity and platelet activation, and ultimately macrophage-mediated plaque inflammation. (ahajournals.org)
  • Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. (inova.org)
  • The past decade has seen major progress in the development of antithrombotic agents that are tailored to ( i ) exhibit antiplatelet activity, ( ii )aidinthelysisofblood clots, or ( iii ) affect the activity and generation of thrombin. (pnas.org)
  • DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. (wikipedia.org)
  • Treatment with the thrombin inhibitor argatroban reversed platelet activation and aortic macrophage accumulation in ApoE-/-/Bgn-/0 mice. (ahajournals.org)
  • At present, three direct thrombin inhibitors (DTI) (lepirudin, argatroban, and bivalirudin) are clinically used for limited indications, whereas there is still no direct FXa inhibitor available. (eurekaselect.com)
  • Consideration needs to be given to other potentially challenging aspects of the clinical management of patients on dabigatran, including the need to understand how to assay for anticoagulation status in patients who have overdosed or need surgery - activated partial thromboplastin time and thrombin time seem to be the most reliable tests. (thefreedictionary.com)
  • Using the scu-PA inactivation assay the dissociation constant for the thrombin-TM interaction was found to be 0.4nM for high-M(r) rec-TM and 14nM for low-M(r) rec-TM. (tudelft.nl)
  • For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. (diva-portal.org)
  • In addition, the capacity of vitreous fluids obtained from patients after oral dabigatran intake was tested in an in vitro thrombin activity assay. (eur.nl)
  • Direct thrombin inhibitors' potential efficacy in Alzheimer's disease. (biomedsearch.com)
  • In this work, a nanocomplexation strategy was developed for modifying the stability and hemostatic efficacy of thrombin, in which a water-soluble cationic amylose derivative containing poly(l-lysine) dendrons was prepared by a click reaction and then used to complex thrombin in an aqueous system. (dovepress.com)
  • In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. (jci.org)
  • Will direct thrombin inhibitor excel with high-dose clopidogrel on bo. (bio-medicine.org)
  • Will direct thrombin inhibitor excel with high-dose clopidogrel on board? (bio-medicine.org)
  • Activity was determined by the direct comparison to NIH Thrombin Reference Standard which uses 200ul of diluted plasma 1:1 with saline as a substrate and 100ul of albumin solution based on a modification of the method of Biggs. (prospecbio.com)
  • ETHICON will market EVITHROM* as both a stand-alone thrombin and in conjunction with an absorbable gelatin sponge such as SURGIFLO* Hemostatic Matrix with FlexTip. (fiercebiotech.com)
  • In a clinical trial involving several hundred subjects, Evithrom was found comparable to cattle-derived thrombin in both safety and effectiveness. (emaxhealth.com)
  • The adsorption and the redox behaviour of thrombin-binding aptamer (TBA) and extended TBA (eTBA) were studied using atomic force microscopy and voltammetry at highly oriented pyrolytic graphite and glassy carbon. (hindawi.com)
  • The 29-mer thrombin aptamer was immobilized on the surface of a GMR device as a recognizing ligand for thrombin detection. (mdpi.com)
  • For this purpose, thiolated 29-mer thrombin-binding aptamers (TBA 29 (12T) SH) as capturing aptamer were immobilized on the surface of silver dendritic nanostructures, then thrombin was sandwiched between the capturing aptamer and Cy5-labeled 15-mer thrombin aptamer (TBA 15- Cy5). (springer.com)