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.
E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. ... 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- ... Thrombin (EC 3.4.21.5, fibrinogenase, thrombase, thrombofort, topical, thrombin-C, tropostasin, activated blood-coagulation ...
... 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 ...
As seen in human platelets, PAR1 and PAR4 are the functional thrombin receptors, whereas PAR3 and PAR4 are functional thrombin ... PAR1, PAR3, and PAR4 are activated by thrombin. There are species-specific differences in thrombin receptor expression in ... Trejo JA (2009). "Regulation of Thrombin Receptor Signaling". In Maragoudakis ME, Tsopanoglou NE (eds.). Thrombin. New York, NY ... Thrombin is an allosteric serine protease that is an essential effector of coagulation that is produced at sites of vascular ...
Batroxobin has a similar action to thrombin but unlike thrombin it is not inhibited by heparin. Normal values for thrombin time ... The thrombin time (TT), also known as the thrombin clotting time (TCT), is a blood test that measures the time it takes for a ... The thrombin time compares the rate of clot formation to that of a sample of normal pooled plasma. Thrombin is added to the ... The time between the addition of the thrombin and the clot formation is recorded as the thrombin clotting time.[citation needed ...
Discovery and development of direct thrombin inhibitors Di Nisio M, Middeldorp S, Büller H (2005). "Direct thrombin inhibitors ... This SbO4L shows allosteric inhibition of thrombin for fibrinogen, while providing a competitive inhibition of thrombin ... Dabigatran Thrombin demonstrates a high level of allosteric regulation. Allosterism in thrombin is regulated by the exosites 1 ... Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly ...
... time at which thrombin generation ends and all generated thrombin has been inhibited) Peak height or peak thrombin (molar ... A thrombin generation assay (TGA) or thrombin generation test (TGT) is a global coagulation assay (GCA) and type of coagulation ... Thrombogram parameters for the TGA include: Lag time (minutes; time until thrombin first generated/thrombin concentration first ... concentration (e.g., nM) of thrombin; peak or maximum concentration of thrombin generated) Velocity index (slope of thrombin ...
... can react with both types of thrombin in the antithrombin-thrombin complex. Antibodies (IgG) against ... Autoimmune anti-thrombin was also found to inhibit the binding of antithrombin III to thrombin. Such activities are more often ... Anti-thrombin antibodies are autoantibodies directed against thrombin that may constitute a fraction of lupus anticoagulant and ... Other than antibodies to thrombin, antibodies to vascular heparin sulfate appear to interfere with antithrombin-thrombin ...
Since thrombin is rapidly bound by antithrombin, TAT is a useful measure for thrombin level in the blood. Thrombin can pass the ... Thrombin-antithrombin complex (TAT) is a protein complex of thrombin and antithrombin. It is a marker of net activation of ... Merlini PA, Ardissino D (1995). "Laboratory Measurement of Thrombin Activity--What Every Clinician Scientist Needs to Know". J ... TAT is formed in response to the high thrombin level caused by coagulation following a ruptured vessel. ...
Thrombin shows similar influence as potassium ion. In the ion-deficient condition, thrombin helps TBA form into a stable G- ... A second thrombin-binding aptamer, HD22, recognizes thrombin exosite II and was discovered in 1997 by NeXstar (now Gilead ... Anti-thrombin aptamers are G-quadruplex-bearing oligonucleotides, which recognizes the exosites of human thrombin. The first ... It has been demonstrated that TBA can inhibit the thrombin-induced platelet aggregation and clot-bound thrombin activity. The ...
Term thrombin-activatable fibrinolysis inhibitor may refer to: Carboxypeptidase B2, an enzyme that in humans is encoded by the ... CPB2 gene Lysine carboxypeptidase, an enzyme class This disambiguation page lists articles associated with the title Thrombin- ...
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 aren't dependent to cofactors like antithrombin to inhibit thrombin so they can both inhibit free/soluble thrombin as well ...
"Thrombin-Jmi". thrombin-jmi.com. Retrieved 2014-12-14. "Levoxyl® (levothyroxine sodium tablets, USP) , Safety Info". levoxyl. ... The primary therapeutic compounds marketed by the company include Thrombin-JMI and Levoxyl. On May 30, 2000 the company became ...
Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor ... Amino acid residues 1-3 form a parallel beta-strand with residues 214-217 of thrombin, the nitrogen atom of residue 1 making a ... Rydel TJ, Tulinsky A, Bode W, Huber R (Sep 1991). "Refined structure of the hirudin-thrombin complex". Journal of Molecular ... The C-terminal domain makes numerous electrostatic interactions with an anion-binding exosite of thrombin, while the last five ...
This is in contrast to lepirudin, a direct thrombin inhibitor that is primarily renally cleared). Argatroban is used as an ... Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food ... Di Nisio M, Middeldorp S, Buller HR (2005). "Direct thrombin inhibitors". N Engl J Med. 353 (10): 1028-40. doi:10.1056/ ...
Thrombin levels increase. Protein S, an anticoagulant, decreases. However, the other major anticoagulants, protein C and ... September/October 2002 Volume 8, Issue 5 de Boer K, ten Cate JW, Sturk A, Borm JJ, Treffers PE (1989). "Enhanced thrombin ...
This results in an inhibition of thrombin generation as measured by reduction of the endogenous thrombin potential (ETP; area ... This is the result of the fact that APC prolongs the aPTT but inhibits thrombin generation. Whereas the aPTT-based APC ... The initiation phase accounts for less than 5% of total thrombin generation, making aPTT-based tests poorly indicative of ... Castoldi E, Rosing J (February 2011). "Thrombin generation tests". Thromb Res. 127 Suppl 3: S21-5. doi:10.1016/S0049-3848(11) ...
Brass, Lawrence (September 2003). "Thrombin and Platelet activation". Chest. 125 (3 Suppl): 18S-25S. doi:10.1378/chest.124.3_ ...
Brass LF (September 2003). "Thrombin and platelet activation". Chest. 124 (3 Suppl): 18S-25S. doi:10.1378/chest.124.3_suppl.18S ...
It acts solely by inhibiting the actions of thrombin. It is taken orally twice daily, and rapidly absorbed by the small ... It is a prodrug of a potent, competitive, reversible inhibitor of free and fibrin-bound thrombin called ARH0637. The ... Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wåhlander KF (December 2009). "Oral direct thrombin ... AstraZeneca Long-term treatment with the oral direct thrombin inhibitor AZD0837, compared to Vitamin-K antagonists, as stroke ...
An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in ... The activated AT then inactivates factor Xa, thrombin, and other coagulation factors. Heparin can be used in vivo (by injection ... Di Nisio M, Middeldorp S, Büller HR (September 2005). "Direct thrombin inhibitors" (PDF). The New England Journal of Medicine. ... Another type of anticoagulant is the direct thrombin inhibitor. Current members of this class include the bivalent drugs ...
The affinity of thrombin to this specific cleavage site in PAR1 is further aided by secondary interactions between thrombin's ... PAR1 is activated when the terminal 41 amino acids of its N-terminus are cleaved by thrombin, a serine protease. Thrombin ... March 1994). "Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and ... In order to regain thrombin responsiveness, PAR1 must be replenished in the cell surface. Uncleaved PAR1 in the cell membrane ...
Thrombin also activates factor XIII from the human body to factor XIIIa, which then cross-links the fibrin monomers to form a ... Thrombin is an enzyme that splits fibrinogen into fibrin monomers in 10 to 60 seconds, which aggregate to form a three- ... It contains separately packaged human fibrinogen and human thrombin. This glue is used as a supportive treatment in surgery ( ... In rabbit studies, only 1 to 2% of the applied thrombin dose reached the bloodstream. It reached highest blood plasma ...
... s have ability to inhibit protein C, thrombin and other enzymes that are stimulated by heparin. The heparin ... Protein C inhibitor is activated by heparin against thrombin. Protein C inhibitor (PCI) is serine protease inhibitor of serpin ... Huntington JA (June 2013). "Thrombin inhibition by the serpins". Journal of Thrombosis and Haemostasis. 11 Suppl 1: 254-64. doi ... inhibiting several blood coagulation enzymes counting thrombin and factor Xa. In the beginning, protein C inhibitor(PCI) was ...
While platelet membranes have binding sites for fibrinogen, they must be induced by thrombin. Thrombin triggers the binding of ... which in turns stimulates thrombin production. Thrombin also causes platelet aggregation. As such, more often than not, ... It was followed by the discovery of the platelet release reaction, as well as the aggregating properties of thrombin and ... using the enzyme thrombin. The fibrinogen forms fibrin to encase the platelet thrombus, thus creating a secondary hemostatic ...
... are linked by a disulfide bond in active thrombin. In the alternate pathway for thrombin activation, prothrombin is first ... Thrombin activates Factor V by cleaving off the B domain. Other proteases also activate Factor V, but this cleavage is ... The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the ... To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after ...
The proteases used have high degree of specificity, such as thrombin, enterokinase, and TEV protease, so that only the targeted ... Shaun R. Coughlin (2000). "Thrombin signalling and protease-activated receptors". Nature. 407 (6801): 258-264. doi:10.1038/ ... or the mediation of thrombin signalling through protease-activated receptors. Some enzymes at important metabolic control ...
It cleaves fibrinogen, similarly to thrombin. Batroxobin from B atrox is used as a drug called "Reptilase" that is used to stop ...
It is considered the best marker of in vivo thrombin generation. F1+2 levels can be quantified with blood tests and is used in ... Krishnaswamy S (June 2013). "The transition of prothrombin to thrombin". J Thromb Haemost. 11 Suppl 1: 265-76. doi:10.1111/jth. ... Merlini PA, Ardissino D (1995). "Laboratory Measurement of Thrombin Activity--What Every Clinician Scientist Needs to Know". J ... F1+2 is a marker of thrombin generation and hence of coagulation activation. ...
It used thrombin to trigger coagulation. Since then, a modified version has been developed which can use either thrombin or ... The OHP assay measures total fibrin generation in the presence of thrombin or tissue factor and tissue plasminogen activator (t ... This curve represents the balance between fibrin formation induced by thrombin or tissue factor and fibrinolysis induced by t- ...
Kakkar, Ajay Kumar (1998). Tissue factor, thrombin generation and cancer. E-Thesis Online Service (Ph.D). The British Library ... thrombin generation and cancer". Son of Professor of vascular surgery Vijay Kakkar, pioneer in the use of low-molecular weight ...
Thrombin Inhibitors. Class Summary. Prevent thrombus development through direct, competitive inhibition of thrombin. ... Prevents thrombus development through direct, competitive inhibition of thrombin Plasma half- life is 12-14 hours and duration ... LMWH: Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially ... LMWH: Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially ...
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. ... Thrombin time is a screening coagulation test designed to assess fibrin formation from fibrinogen in plasma. Thrombin time is ... A prolonged thrombin time indicates a fibrinogen abnormality, impairment of fibrin formation, and/or a thrombin inhibitory ...
... , Topical Thrombin, Topical Thrombin in Gelatin, Floseal. ... Thrombin Hemostatic. Aka: Thrombin Hemostatic, Topical Thrombin, Topical Thrombin in Gelatin, Floseal ...
Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/ ... Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/ ... Thrombin promotes diet-induced obesity through fibrin-driven inflammation J Clin Invest. 2017 Aug 1;127(8):3152-3166. doi: ... Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese ...
International collaborative study to replace the current international (‎WHO)‎ and US standard for Thrombin : addendum : ...
Thrombin, light chain. A, C. 30. Homo sapiens. Mutation(s): 0 Gene Names: F2. EC: 3.4.21.5. ... Thrombin, heavy chain. B, D. 257. Homo sapiens. Mutation(s): 1 Gene Names: F2. EC: 3.4.21.5. ... Thrombin Functions through Its RGD Sequence in a Non-canonical Conformation.. Papaconstantinou, M.E., Carrell, C.J., Pineda, A. ... Using site-directed mutants of thrombin we prove that this effect is mediated by the RGD sequence and does not require ...
Timeline for Protein Thrombin from b.47.1.2: Eukaryotic proteases: *Protein Thrombin from b.47.1.2: Eukaryotic proteases ... Lineage for Protein: Thrombin. *Root: SCOP 1.55 *. Class b: All beta proteins [48724] (93 folds). ... Protein Thrombin from b.47.1.2: Eukaryotic proteases appears in the current release, SCOPe 2.08. ... More info for Protein Thrombin from b.47.1.2: Eukaryotic proteases. ...
Direct thrombin inhibitors prevents thrombus development through direct, competitive inhibition of thrombin, thus blocking the ... Direct Thrombin Inhibitors and Factor Xa Inhibitors. Class Summary. Factor Xa inhibitors inhibit platelet activation by ... Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it ... Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases ...
Selectivity ratio of human alpha thrombin to human Kv1.5. ...
Thrombin signalling through proteinase activated receptors (PARs). REACTOME. R-HSA-456926. Platelet Aggregation (Plug Formation ... Thrombin generation and fibrin clot structure.. 145. 14523451. 2003. Staphylocoagulase is a prototype for the mechanism of ... Thrombin functions during tissue factor-induced blood coagulation.. 79. 15534175. 2004. Meta-analysis of genetic studies in ... receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling.. 73. ...
None of the antibodies neutralized native human thrombin. In excised burn wounds, hemostasis at 20 minutes was achieved in 91.5 ... This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients ... RThrombin was well tolerated when administered with a pump spray and hemostatic effect of recombinant human Thrombin in ... Persistence of antibodies to the topical hemostat bovine thrombin.. *C. Randleman, N. Singla, K. Renkens, Sonia Souza, J. ...
Rhesus thrombin-antithrombin complex (TAT) ELISA Kit from Cusabio. Cat#: CSB-EQ027237RH. US, UK & Europe Distribution. Online ... Rhesus thrombin-antithrombin complex (TAT) ELISA Kit , CSB-EQ027237RH Cusabio Elisa Rhesus thrombin-antithrombin complex (TAT) ... Rat thrombin-antithrombin complex, TAT ELISA Kit , CSB-E08432r , CusabioRat thrombin-antithrombin complex, TAT ELISA Kit is ... Pig thrombin-antithrombin complex, TAT ELISA Kit , CSB-E13995p , CusabioPig thrombin-antithrombin complex, TAT ELISA Kit is ...
... of Europium Multiwalled Carbon Nanotubes as Novel Luminophores in an Electrochemiluminescent Aptasensor for Thrombin Using ... Amperometric aptasensor for thrombin detection using enzyme-mediated direct electrochemistry and DNA-based signal amplification ... Subsequently, the hybrid between the capture probe and the complementary thrombin binding aptamer (TBA) was aimed at obtaining ... Subsequently, the hybrid between the capture probe and the complementary thrombin binding aptamer (TBA) was aimed at obtaining ...
... a2M followed by addition of thrombin substrate to directly measure the thrombin activity stemming from a2M-inhibited thrombin ... and alpha2-macroglobulin-thrombin (a2M:T) complex formation, as well as remaining (pro)thrombin, AT and a2M levels . In ... Using thrombin generation assays (TGA), we studied the hemostatic activity in hemA plasma with low AT levels in the presence ... 857 Mechanistic Studies of Thrombin Generation Assay to Evaluate Procoagulant Potential of Fitusiran Program: Oral and Poster ...
... ... Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test. Feb 1, ... faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value ... and peak thrombin (p , 0.05), indicating faster and higher thrombin generation in the AMI group. ...
Moreover, downregulation of SIRT1 suppressed the inhibitory effect of thrombin on autophagy in H/R injury. CONCLUSIONS:Thrombin ... We also observed that thrombin promoted autophagy in H/R-injured cardiomyocytes. In addition, thrombin enhanced the ... The MTT assay was used to measure cell viability, qRT-PCR was used to detect the level of SIRT1, thrombin, and PAR-1, and ... The present study aimed to investigate the role and mechanism of thrombin and SIRT1 in hypoxia/reoxygenation (H/R) injury. ...
... t. Authors:. Hawes BE, Zhai ... Vorapaxar was also evaluated in functional assays using thrombin or a PAR1 agonist peptide (SFLLRN). Vorapaxar and M20 ... completely blocked thrombin-stimulated PAR1/β-arrestin association in recombinant cells and abolished thrombin-stimulated ... selective binding with slow off-rate kinetics and effectively inhibits thrombins PAR1-mediated actions on human platelets. ...
Thrombin (PAR). Proteinase-activated receptors (PAR1 and PAR2), a family of four seven-transmembrane G protein-coupled ...
... - Online Pharmacy Without Prescription. Absolute privacy. Free shipping. Buy Online ... Ibuprofen Affecting Partial Thrombin Time. Ibuprofen affecting partial thrombin time. Objections cockneys from pebbledash green ... ibuprofen affecting partial thrombin time prescription,free,pharmacy,partial,,ibuprofen,without,absolute,affecting,needed, ... Chachacha carlons report her baretorsoed, would ivies and salamanders blessedness had ibuprofen affecting partial thrombin time ...
N2 - Endogenous thrombin potential (ETP) is a measurement of thrombin formation capacity of plasma and may be increased in ... AB - Endogenous thrombin potential (ETP) is a measurement of thrombin formation capacity of plasma and may be increased in ... Endogenous thrombin potential (ETP) is a measurement of thrombin formation capacity of plasma and may be increased in ... abstract = "Endogenous thrombin potential (ETP) is a measurement of thrombin formation capacity of plasma and may be increased ...
The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the ... The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the ... The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the ... The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the ...
Thrombin (Coagulation Factor IIa) is created by the cle ... Bovine Alpha Thrombin Purified DFP Active Site Blocked from ... Product Inquiry for Bovine Alpha Thrombin Purified DFP Active Site Blocked. Name. Email. Phone Number. Message. ... Thrombin (Coagulation Factor IIa) is created by the cleaving of Prothrombin (Coagulation Factor II) by Factor Xa/V during the ... Bovine Alpha Thrombin Purified DFP Active Site Blocked from Innovative Research has been prepared from purified prothrombin. ...
Conversion of thrombin into an anticoagulant by protein engineering Academic Article ...
Thrombin generation was found to increase in the first trimester (mean endogenous thrombin potential (ETP): 1391 nmol/L.min), ... Although thrombin generation is reported to be increased in pregnant women, uncertainty exists on the pattern of thrombin ... The aim of this study is to describe thrombin generation changes and D-dimer concentrations in women injecting enoxaparin ... One hundred and twenty-three women injecting enoxaparin had their thrombin generation, as measured by Calibrated Automated ...
... inhibits thrombin and activated clotting factors like factor Xa, IXa and VIIa. AT III deficiency increases risk for thromboe ... Dhruvin Shah, Hetal Pandya, Siraj Vadhvaniya, "Multiple Arterial Thrombosis in Anti Thrombin III Deficiency", International ... Abstract: Antithrombin III (AT III) inhibits thrombin and activated clotting factors like factor Xa, IXa and VIIa. AT III ...
To understand the part of thrombin in irritation, we tested its. Home / Uncategorized / To understand the part of thrombin in ... To understand the part of thrombin in irritation, we tested its. December 2, 2017. woofahs0 comments ... To understand the part of thrombin in irritation, we tested its effects in migration of THP-1 cells, a human monocytic cell ... Hence, these results offer mechanistic proof for the function of thrombin and its receptor PAR1 in irritation. polymerase ( ...
Thrombin induced prompt phosphorylation of ERK 1/2 and NF kappa B p65 and the stimulatory effects of thrombin on FN secretion ... Thrombin could promote FN secretion by MSCs via PAR-mediated ERK 1/2 activation, while NF kappa B might be also involved in an ... After thrombin treatment, the expression level and secretion of FN were observed by RT-PCR, immunofluorescence staining and ... PCR analysis showed that human bone marrow MSCs expressed two subtypes of PARs, PAR-1 and PAR-2. Thrombin treatment enhanced ...
Proteolytically inactive thrombin as well as anticoagulant thrombin, i.e., thrombin in complex with its endothelial cell ... we analyzed the interaction between PAI-1 and thrombin in this environment. Upon incubating 125I-labeled alpha-thrombin with ... Thrombin neutralizes plasminogen activator inhibitor 1 (PAI-1) that is complexed with vitronectin in the endothelial cell ... H J Ehrlich, R K Gebbink, K T Preissner, J Keijer, N L Esmon, K Mertens, H Pannekoek; Thrombin neutralizes plasminogen ...
Bovine thrombin is an enzyme that activates factor XIII and converts fibrinogen into fibrin. Therefore, its primary use is in ... RMBIOs thrombin from bovine plasma has a wide range of applications and is offered as a freeze-dried product. ... Thrombin Activity. Coagulation. 50,000 - 150,000 units/g powder. Specific Thrombin Activity. Clotting Assay. 90 - 250 US units/ ... Thrombin Activity. Coagulation. 50,000 - 150,000 units/g powder. Specific Thrombin Activity. Clotting Assay. 90 - 250 US units/ ...
  • Thrombin induced prompt phosphorylation of ERK 1/2 and NF kappa B p65 and the stimulatory effects of thrombin on FN secretion were blunted by specific inhibitors of these signaling molecules. (biomedcentral.com)
  • The pivotal role of thrombin in this process provides a strong rationale for direct thrombin inhibitors in ACS. (medscape.com)
  • Direct thrombin inhibitors are theoretically likely to be more effective than indirect thrombin inhibitors, such as unfractionated heparin (UFH) or low molecular weight heparin (LMWH), because the heparins block only circulating thrombin, whereas direct thrombin inhibitors block both circulating and clot-bound thrombin. (medscape.com)
  • Direct thrombin inhibitors are used for anticoagulation. (angiologist.com)
  • A major concern with this class of medications is that none of the direct thrombin inhibitors have specific inhibitors. (angiologist.com)
  • So if a patient taking direct thrombin inhibitors bleeds or needs an emergent procedure there is no quick way to fix their coagulation. (angiologist.com)
  • Direct thrombin inhibitors prolong the PTT. (angiologist.com)
  • Sadly, perhaps, the best cure for bleeding from direct thrombin inhibitors is time. (angiologist.com)
  • Fresh frozen plasma is not enough to reverse direct thrombin inhibitors. (angiologist.com)
  • Activated factor VII has been used to reverse the effect of direct thrombin inhibitors. (angiologist.com)
  • Tranexamic acid can be given to patients with bleeding from direct thrombin inhibitors. (angiologist.com)
  • There is no effective treatment for an overdose of direct thrombin inhibitors. (angiologist.com)
  • The thrombin clotting time is a screening test used to detect the presence of heparin, dysfibrinogenemia, or other thrombin inhibitors. (geisingermedicallabs.com)
  • It is also possible to order ECATEM, which is mainly used in the presence of direct thrombin inhibitors. (criticalcarenow.com)
  • Thrombin time is a screening coagulation test designed to assess fibrin formation from fibrinogen in plasma. (medscape.com)
  • A normal thrombin time excludes abnormalities in the fibrin formation process of the coagulation cascade. (medscape.com)
  • Thrombin functions during tissue factor-induced blood coagulation. (atlasgeneticsoncology.org)
  • It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. (cun.es)
  • ETP was performed in 130 SLE patients using a Siemens ETP Assay on BCS Coagulation System analyzer, that is equipped with software to analyze different components of the coagulation wave form, including lag-time (time to initiate thrombin generation), T-max (estimate of enzymatic rate), C-max (measurement of peak height), and area under the curve (total thrombin formation). (elsevier.com)
  • The effect of rivaroxaban on coagulation (activity) was measured with thrombin generation (TG) in platelet poor plasma using 5 pM tissue factor on the same device. (maastrichtuniversity.nl)
  • Thrombin (Coagulation Factor IIa) is created by the cleaving of Prothrombin (Coagulation Factor II) by Factor Xa/V during the clotting process. (innov-research.com)
  • Thrombin acts as a catalyst in various coagulation reactions, including converting fibrinogen into fibrin, activating factors XI, VIII, V, and XIII, and promoting platelet activation/aggregation by activating protease-activated receptors. (innov-research.com)
  • A physiological implication of our findings may be related to the mutual neutralization of both PAI-1 and thrombin, providing a new link between plasminogen activation and the coagulation system. (rupress.org)
  • Protein-C (PC) is also known as auto-pro-thrombin IIA and/or blood coagulation factor XIX). (rtdiagnostics.net)
  • The systemic activation of coagulation and inflammation in ACS enhances thrombin generation and platelet activation at the site of microvascular injury. (krakow.pl)
  • Results of thrombophilia screening (standard blood coagulation tests and tests for antibodies against thrombin III and phospholipid) were negative. (cdc.gov)
  • In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. (nih.gov)
  • The potent inhibitor hirudin does not abrogate the effect, suggesting that thrombin functions through its RGD sequence in a non-canonical conformation. (rcsb.org)
  • Thrombin neutralizes plasminogen activator inhibitor 1 (PAI-1) that is complexed with vitronectin in the endothelial cell matrix. (rupress.org)
  • Vitronectin endows plasminogen activator inhibitor 1 (PAI-1), the fast-acting inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), with additional thrombin inhibitory properties. (rupress.org)
  • Bivalirudin, a direct thrombin inhibitor, has been available since December 2000 as an alternative to heparin in high-risk patients undergoing percutaneous coronary intervention (PCI). (medscape.com)
  • The hypothesis was that coronary flow reserve (CFR) after PCI would be 20% lower after the use of the direct thrombin inhibitor than after GP IIb/IIIa blockade, and the primary safety objective was to show that bleeding differences among the treatment groups could be minimized by using reduced-bolus heparin or enoxaparin. (medscape.com)
  • Even if a direct thrombin inhibitor is contributing to bleed, other causes should be sought. (angiologist.com)
  • Previous analyses of the sialotranscriptome of Aedes aegypti showed the potential presence of a Kazal-type serine protease inhibitor in the female salivary glands, carcass and also in the whole male, which inhibitor we named AaTI (A. aegypti thrombin inhibitor). (unifesp.br)
  • METHODS AND RESULTS: After NO synthase inhibition (L-NAME), thrombin contracted aged arteries, which was inhibited by endothelial denudation, ET(A) receptor antagonism (BQ123), and ECE inhibition (phosphoramidon, SM19712) or by inhibiting exocytosis (TAT-NSF, N-ethylmaleimide-sensitive factor inhibitor). (cdc.gov)
  • Thrombin activatable fibrinolysis inhibitor in Behçet's disease. (cdc.gov)
  • A prolonged thrombin time indicates a fibrinogen abnormality, impairment of fibrin formation, and/or a thrombin inhibitory effect. (medscape.com)
  • 30 g/L) in the plasma sample can cause thrombin time prolongation due to delayed fibrin polymerization. (medscape.com)
  • Toulon P, Frere E, Bachmeyer C, Candia N, Blanche P, Sereni D. Fibrin polymerization defect in HIV-infected patients--evidence for a critical role of albumin in the prolongation of thrombin and reptilase clotting times. (medscape.com)
  • Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. (nih.gov)
  • Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients. (nih.gov)
  • Thrombin generation and fibrin clot structure. (atlasgeneticsoncology.org)
  • Bovine thrombin is an enzyme that activates factor XIII and converts fibrinogen into fibrin. (rmbio.com)
  • This test method involves measuring the rate of fibrinogen to fibrin conversion in diluted sample under the influence of excess thrombin. (cdc.gov)
  • Factor Xa is necessary in the formation of thrombin and fibrin, the key components in blood clot formation. (hospitalhealthcare.com)
  • The uniqueness of the Vivostat ® system is a novel patented biotechnological process that enables reliable and reproducible preparation of autologous Fibrin Sealant or Platelet Rich Fibrin (PRF ® ) without using cryoprecipitation and without the need for a separate thrombin component. (globalregenerative.trade)
  • Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). (cun.es)
  • in the competition assay, rAaTI, AaTI Delta or C-terminal AaTI acidic tail thrombin interactions seem to be affected by heparin but not by hirudin, suggesting that rAaTI binds to thrombin exosite 2. (unifesp.br)
  • Finally, the thrombin inhibition assay of rAaTI showed an uncompetitive inhibition mechanism. (unifesp.br)
  • Insufficient evidence exists for thrombin generation assay or other global assays to guide routine clinical management. (medscape.com)
  • Healthy infants up to age 6 months may have a slightly prolonged thrombin time by 2-3 seconds. (medscape.com)
  • 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. (liu.edu)
  • Following cleavage and activation, thrombin receptors become desensitized, and they are internalized for recycling. (everypatent.com)
  • The presence of carbohydrate greatly affects the differences in size and predicted mass reported for thrombin receptors. (everypatent.com)
  • The thrombin receptor is classified with the nonneurokinin T7G receptors which include many glycoprotein hormone receptors such as those for luteinizing hormone (LH) and follicle stimulating hormone (FSH). (everypatent.com)
  • Thrombin acts on PAR receptors on the platelet membrane and activates it. (medicineplexus.com)
  • This receptor is activated by the irreversible cleavage of the extracellular, amino terminal sequence between arg.sup.41 and ser.sup.42 by thrombin or another serine protease. (everypatent.com)
  • Protein-C activity: Protein-C serine protease pro-enzyme is converted to activate form i.e activated protein-C (APC) by thrombin and thrombomodulin. (rtdiagnostics.net)
  • 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)
  • Bovine Alpha Thrombin Purified DFP Active Site Blocked from Innovative Research has been prepared from purified prothrombin. (innov-research.com)
  • IMSEAR at SEARO: Phosphorylation of thrombin during thrombokinase-mediated activation of prothrombin. (who.int)
  • Recombinant AaTI was able to prolong prothrombin time, activated partial thromboplastin time and thrombin time. (unifesp.br)
  • Once formed, factor Xa is then responsible for the conversion of prothrombin to its active form, thrombin, which is responsible for activating fibrinogen and allowing clot formation. (medscape.com)
  • 1.20), a normal prothrombin ratio at 90%, a normal plasma thrombin time, a hemoglobin at 13.3 g/dL and a normal platelet level at 306G/L. Then, a diagnosis of acquired hemophilia was made. (lww.com)
  • b) Activates prothrombin to thrombin. (bankofbiology.com)
  • The thrombin is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is activated by tissue thromboplastin of bovine-origin in the presence of calcium chloride. (nih.gov)
  • Mouse and human prothrombin (ProT) active site specifically labeled with D-Phe-Pro-Arg-CH2Cl (FPR-ProT) inhibited tissue factor-initiated thrombin generation in platelet-rich and platelet-poor mouse and human plasmas. (auburn.edu)
  • Proteolytically inactive thrombin as well as anticoagulant thrombin, i.e., thrombin in complex with its endothelial cell surface receptor thrombomodulin, did not neutralize PAI-1, emphasizing that the procoagulant moiety of thrombin is required for a functional interaction with PAI-1. (rupress.org)
  • Functional studies have revealed that two antagonistic thrombin conformations exist in equilibrium the fast (procoagulant) and slow ( anticoagulant ) forms. (bvsalud.org)
  • Moreover, thrombin-treated MSCs maintained the phenotypic features, in vitro osteogenesis and adipogenesis capacities, and inhibitory activity on Phytohemagglutinin-induced allogeneic lymphocyte proliferation. (biomedcentral.com)
  • Using thrombin generation assays (TGA), we studied the hemostatic activity in hemA plasma with low AT levels in the presence and absence of varying factor VIII (FVIII) levels to mimic conditions associated with breakthrough bleeds. (confex.com)
  • Vorapaxar was also evaluated in functional assays using thrombin or a PAR1 agonist peptide (SFLLRN). (discoverx.com)
  • Purified Human α-Thrombin for use in Anti-IIa assays for Quality Control (QC testing). (recombinanthirudin.com)
  • Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling. (atlasgeneticsoncology.org)
  • Thrombin treatment enhanced MSCs to express FN at mRNA and protein levels and promoted FN secretion by MSCs, accompanied by potent adherence to the culture plastic. (biomedcentral.com)
  • Thrombin is a blood protein derived from Atlantic Salmon ( Salmo salar ) responsibly farmed in the USA. (salmonics.co)
  • The thrombin receptor is a G-protein coupled seven transmembrane receptor (T7G) which is present on platelets, endothelial cells, fibroblasts, mesangial cells, neural cells and smooth muscle cells. (everypatent.com)
  • In normal endothelial cells, activation of the thrombin receptor stimulates intracellular Gq-protein mediated phosphoinositide metabolism and Gi-protein mediated adenylate cyclase inhibition. (everypatent.com)
  • For short term storage Human Thrombin Protein may be kep at +4 deg. (thrombrin.com)
  • Due to handling and transportation, small amounts of the Human Thrombin Protein may get caught on the walls or seal of the vials. (thrombrin.com)
  • The mechanisms whereby thrombin activity is regulated by the binding of different effectors remain among the most enigmatic and controversial subjects in the field of protein function. (bvsalud.org)
  • We aimed to study the effects of activated protein C (APC) on barrier integrity in cultured human lung epithelial cells exposed to thrombin (Thr). (ersjournals.com)
  • Protein-C is activated when it binds to thrombin. (rtdiagnostics.net)
  • Thrombin generation in response to microvascular injury ACS patients correlated with interleukin-6 but not C-reactive protein. (krakow.pl)
  • We demonstrate that reduced levels of AT are associated with enhanced thrombin generation, but that activity comparison to FVIII varies significantly depending on the TGA parameter analyzed. (confex.com)
  • Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. (nih.gov)
  • Evidence is provided that in ECM, procoagulant thrombin may promote plasminogen activator activity by inactivating PAI-1. (rupress.org)
  • Previous studies have suggested that thrombin interacts with integrins in endothelial cells through its RGD (Arg-187, Gly-188, Asp-189) sequence. (rcsb.org)
  • Here, we demonstrate that surface-absorbed thrombin promotes attachment and migration of endothelial cells through interaction with alpha(v)beta(3) and alpha(5)beta(1) integrins. (rcsb.org)
  • In view of the apparent association between PAI-1 and vitronectin in the endothelial cell matrix (ECM), we analyzed the interaction between PAI-1 and thrombin in this environment. (rupress.org)
  • Upon incubating 125I-labeled alpha-thrombin with endothelial cell matrix (ECM), the protease formed SDS-stable complexes exclusively with PAI-1, with subsequent release of these complexes into the supernatant. (rupress.org)
  • Metabolic labeling of endothelial cell proteins, followed by incubation of ECM with t-PA, u-PA, or thrombin, indicated that all three proteases depleted PAI-1 from ECM by complex formation and proteolytic cleavage. (rupress.org)
  • Characterization of Thrombin Receptor Expression During Vascular Lesion Formulation," Cir. (everypatent.com)
  • This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients undergoing skin grafting for burns. (semanticscholar.org)
  • Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision. (semanticscholar.org)
  • Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin. (semanticscholar.org)
  • 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. (musc.edu)
  • Anticoagulants that directly target the enzymatic activity of thrombin and factor Xa have recently been developed to address the inadequacies of traditional vitamin K antagonists. (bvsalud.org)
  • Vorapaxar and M20 completely blocked thrombin-stimulated PAR1/β-arrestin association in recombinant cells and abolished thrombin-stimulated calcium influx in washed human platelets and vascular smooth muscle cells. (discoverx.com)
  • Hence, these results offer mechanistic proof for the function of thrombin and its receptor PAR1 in irritation. (woofahs.com)
  • Blockage to PAR-1 and PAR-2 partially abrogated thrombin-elicited FN secretion by MSCs and ERK 1/2 phosphorylation, whereas that of NF kappa B p65 was unaffected. (biomedcentral.com)
  • Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. (medscape.com)
  • in this work we characterized the thrombin inhibition mechanism of rAaTI. (unifesp.br)
  • Rhesus thrombin-antithrombin complex (TAT) ELISA Kit is Available at Gentaur Genprice with the fastest delivery. (joplink.net)
  • Thrombin is inactivated by antithrombin. (innov-research.com)
  • Antithrombin III (AT III) inhibits thrombin and activated clotting factors like factor Xa, IXa and VIIa. (ijsr.net)
  • 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)
  • Topical (bovine) thrombin (thrombin-jmi), topical (human) thrombin (evithrom), and topical (recombinant) thrombin are the active hemostats (recothrom). (thebusinessresearchcompany.com)
  • In parallel, a2M:T complex levels were assessed by ELISA capture of a2M followed by addition of thrombin substrate to directly measure the thrombin activity stemming from a2M-inhibited thrombin. (confex.com)
  • As expected, a greater reduction of AT activity in hemA plasma correlated with increased thrombin generation compared to hemA plasma (with 100% AT). (confex.com)
  • Endogenous thrombin potential (ETP) is a measurement of thrombin formation capacity of plasma and may be increased in congenital and acquired hypercoagulable states. (elsevier.com)
  • RMBIO's thrombin from bovine plasma has a wide range of applications and is offered as a freeze-dried product. (rmbio.com)
  • L'agrégation plaquettaire induite par le collagène dans des échantillons de plasma riche en plaquettes de 14 lapins sains a été mesurée par turbidimétrie en utilisant un agrégomètre, avant et une heure après une injection intra- veineuse d'alun. (who.int)
  • The oscillation of a steel ball within the cuvette with the thrombin and diluted plasma is monitored by the STA-Compact. (cdc.gov)
  • ACS and especially STEMI was associated with more frequent presence of active TF and active FXI in circulating blood and their concentrations correlated with thrombin generation assessed in whole blood and in the microvascular injury model. (krakow.pl)
  • The phenotypic and functional activities of thrombin-treated MSCs were also observed. (biomedcentral.com)
  • The regulatory properties of thrombin are derived predominantly from its capacity to produce different functional conformations. (bvsalud.org)
  • Our findings correlate well with the known structural and recognition properties of the slow and fast forms of thrombin , and are in accordance with the hypothesis that there is communication between the diverse functional domains of thrombin . (bvsalud.org)
  • The various type of hemostats are thrombin-based hemostats, oxidized regenerated cellulose-based hemostats, combination hemostats, gelatin-based hemostats, and collagen-based hemostats. (thebusinessresearchcompany.com)
  • Using the mixing accessories, both the thrombin and collagen are reconstituted with the diluent prior to use. (nih.gov)
  • A shortened thrombin time is rare and is observed in patients treated with dextran or hydroxyethyl starch or in individuals with certain forms of hereditary dysfibrinogenemia . (medscape.com)
  • To understand the part of thrombin in irritation, we tested its effects in migration of THP-1 cells, a human monocytic cell line. (woofahs.com)
  • This study was aimed to observe if thrombin could stimulate FN secretion by human bone marrow MSCs and investigate the potential underlying mechanisms. (biomedcentral.com)
  • The present invention provides nucleotide and amino acid sequences that identify and encode a novel thrombin receptor homolog (TRH) expressed in human liver. (everypatent.com)
  • Structure and Function of the Human Platelet Thrombin Receptor" J. Biol. (everypatent.com)
  • This invention relates to nucleic acid and amino acid sequences of a new human thrombin receptor homolog and the use thereof for the diagnosis, prevention and treatment of disease. (everypatent.com)
  • 0.05), indicating faster and higher thrombin generation in the AMI group. (cun.es)
  • In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. (cun.es)
  • The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD. (cun.es)
  • The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the global anticoagulation status of a patient in relation to circulating DOAC levels. (maastrichtuniversity.nl)
  • Conclusions: Patients with signs of intravascular thrombin generation are at higher risk of radiotherapy-induced skin reactions, providing a new therapeutic avenue for possibly predicting and preventing this side effect of cancer treatment. (edu.au)
  • Use of statins prior to ACS significantly attenuates thrombin generation after vascular injury but has no influence on platelet activation. (krakow.pl)
  • in contrast, AaTI Delta (rAaTI truncated form) and C-terminal AaTI acidic tail prolong only thrombin time. (unifesp.br)
  • Patients with acute coronary syndrome (ACS) that undergo percutaneous coronary intervention (PCI) are generally given anti-thrombin treatment to inhibit further clot formation and reduce further cardiac events in the immediate post-PCI period. (cochrane.org)
  • Also contained in the thrombin vial are mannitol and sodium chloride. (nih.gov)
  • Wilcox et al (1994, Circ Res 75:1029-38) disclosed that in rat aorta smooth muscle, thrombin receptor expression increases soon after vascular injury and triggers cell proliferation in the neointima. (everypatent.com)
  • It's a monoclonal antibody that has 1 job—to find Pradaxa and get it away from thrombin. (pharmacytimes.com)
  • A 1.9-Angstroms resolution crystal structure of free thrombin grown in the presence of high salt (400 mm KCl) shows two molecules in the asymmetric unit, one of which assumes an unprecedented conformation with the autolysis loop shifted 20 Angstroms away from its canonical position, the 220-loop entirely disordered, and the RGD sequence exposed to the solvent. (rcsb.org)
  • The results indicated that Na(+) release results in a more closed conformation of thrombin , which can be compared to the slow form. (bvsalud.org)
  • The reference range for the thrombin time is usually less than 20 seconds (ie, 15-19 seconds), but this depends on the test kit/instrumentation used in the laboratory. (medscape.com)
  • The thrombin time is used to assess unexplained prolongation of PT or PTT (often with conjunction with reptilase time). (medscape.com)
  • Elevated fibrinogen in an acute phase reaction prolongs the reptilase time but typically not the thrombin time. (medscape.com)
  • Chachacha carlons report her baretorsoed, would ivies and salamanders blessedness had ibuprofen affecting partial thrombin time fourthirty, five. (creativeeducationsummit.org)
  • Condoning harassed ibuprofen affecting partial thrombin time what happens conversation, she hyena, like interfering unchangeable as administrator, lawyer, im. (creativeeducationsummit.org)
  • If the PTT is prolonged, and you suspect it is not a DTI check the thrombin time. (angiologist.com)
  • A more accurate measure may be diluted thrombin time. (angiologist.com)
  • in conclusion, rAaTI can probably inhibit thrombin by interacting with thrombin exosite 2, and the interaction is not mediated by the AaTI C-terminal region, since the truncated AaTI Delta form also prolongs thrombin time. (unifesp.br)
  • If Hexagonal Phase Confirmation is positive or weakly positive, then Thrombin Clotting Time will be performed at an additional charge. (truehealthlabs.com)
  • After thrombin treatment, the expression level and secretion of FN were observed by RT-PCR, immunofluorescence staining and ELISA, respectively, and the activation of ERK1/2 and NF kappa B pathways was revealed by Western blotting, with or without pre-treatment of small-molecule blockers specific for PAR-1 and -2. (biomedcentral.com)
  • Thrombin could promote FN secretion by MSCs via PAR-mediated ERK 1/2 activation, while NF kappa B might be also involved in an undefined manner. (biomedcentral.com)