Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paeonia lactiflora with the action of promoting blood circulation and removing blood stasis had been shown to be able to inhibit thrombosis and platelet aggregation, increase fibrinolytic activity and promote thrombolysis. This paper described the influence of the extract of Paeonia lactiflora in vitro experiments on prothrombin time (PT), activated partial thromboplastin time (PTT), antithrombin effect, activity of plasminogen and urokinase. The experimental results showed that: (1) The extract of Paeonia lactiflora prolonged the time of PT and PTT. (2) The extract of drug was able significantly to inhibit the thrombin. (3) In study of fibrinolysis by fibrin standard plate experiments, the drug possessed activative effect on the plasminogen. (4) The activity of urokinase was reduced, while the extract of Paeonia lactiflora existed. The inhibitory effect on thrombin and effective effect on plasminogen of the drug might be an important mechanism of its action of promoting blood circulation and removing blood stasis.
...
PMID:[Effect of an extract of Paeonia lactiflora on the blood coagulative and fibrinolytic enzymes]. 236 61

A highly selective inhibitor of plasma-kallikrein (PK), N-(trans-4-aminomethylcyclohexylcarbonyl)-L-phenylalanine 4-carboxymethyl-anilide hydrochloride, was designed and synthesized by the authors' group, called PKSI-527 in our laboratories. (I) PKSI-527 inhibited PK with a Ki value of 0.81 microM. By contrast, the Ki values for glandular kallikrein (GK), plasmin, thrombin, urokinase and factor Xa were greater than 500 microM, 390 microM, greater than 500 microM, 200 microM and greater than 500 microM, respectively. (II) Effects of PKSI-527 on bradykinin (BK) generation, coagulation and fibrinolysis by contact activation were examined using human plasma. (a) BK generation induced by kaolin appeared to be reduced by PKSI-527. Furthermore BK generation induced by lambda-carrageenan, a strong inflammatory agent, was also reduced by PKSI-527. (b) Partial thromboplastin time (PTT) was prolonged by PKSI-527, indicating the suppression of the intrinsic coagulation system. (c) Euglobulin clot lysis time (ECLT) of plasma which was shortened by activation with kaolin, was prolonged by the addition of PKSI-527, confirming the participation of PK in contact-fibrinolysis. These results indicate that PKSI-527 shows great potential in elucidating the significance of PK, and as such deserves further investigation.
...
PMID:Effect of a highly selective plasma-kallikrein synthetic inhibitor on contact activation relating to kinin generation, coagulation and fibrinolysis. 238 57

Hetastarch, the currently marketed preparation of hydroxyethyl starch, affects coagulation by prolonging partial thromboplastin, prothrombin, and bleeding times; by lowering clotting proteins such as fibrinogen via hemodilution; by lowering clotting factor VIII (coagulant, von Willebrand antigen, and von Willebrand activity) to a greater degree than can be explained simply by hemodilution (i.e., presumably factor VIII affected by both hemodilutional plus additional, independent effects); and, finally, by shortening thrombin, reptilase, and urokinase-activated clot lysis times. Pentastarch, a new analog of hetastarch, was found to exert lesser effects on blood coagulation, despite its greater hemodiluting properties. When compared with hetastarch, pentastarch had little effect on factor VIII (except that due to hemodilution), shortened thrombin times to a significantly lesser degree, exerted no effect on the urokinase-activated clot lysis time, and did not prolong the bleeding time. Even when plasma hydroxyethyl starch levels were similar, pentastarch seemed to alter the results of coagulation assays to lesser degree than did hetastarch, which suggests the possibility of greater safety. Therefore, pentastarch may be a desirable drug, not only for leukapheresis, but also for plasma volume expansion in trauma and surgical patients who often have additional hemostatic abnormalities that place them at increased risk of hemorrhage.
...
PMID:Pentastarch may cause fewer effects on coagulation than hetastarch. 245 88

The [Arg15,Glu52]aprotinin gene has been constructed from a synthetic [Glu52]-aprotinin gene via an exchange of the appropriate DNA cassette. The gene has been fused to the N-terminal part of the bacteriophage MS-2 polymerase and expressed in a temperature inducible E. coli expression system. The produced fusion protein is deposited as inclusion bodies. Pure and functionally active [Arg15,Glu52]aprotinin has been obtained after cleavage of the purified fusion protein and renaturation of the aprotinin homologue. Recombinant [Arg15,Glu52]aprotinin shows good inhibition of human anionic and cationic trypsin (Ki less than or equal to 10(-11)M) and of human plasma kallikrein (Ki = 3.2 x 10(-10)M). The inhibition constants for human plasmin are Ki = 1.3 x 10(-10)M and for human urinary kallikrein Ki = 10(-11)M. No inhibition was found with the human proteinases thrombin, coagulation factor Xa, urokinase, tissue plasminogen activator, cathepsin G, leukocyte elastase and pancreatic elastase.
...
PMID:Expression, isolation and characterization of recombinant [Arg15,Glu52]aprotinin. 246 33

Plasma protein C inhibitor (PCI) was purified to homogeneity (greater than 95%) with good recovery (greater than 25%) and reproducibility, and the inhibition of a number of blood clotting and fibrinolytic enzymes by purified PCI was studied. PCI inhibited activated protein C (APC), two-chain urokinase (2c-uPA), two-chain tissue plasminogen activator (2c-tPA), thrombin, factor Xa, plasma kallikrein and factor XIa, and this inhibition was accelerated by heparin. The inhibition of each enzyme was accompanied by formation of enzyme inhibitor complexes and by degradation of the inhibitor to lower molecular weight derivatives. Plasma kallikrein and factor XIa cleaved PCI of native Mr = 57,000 into two products with Mr = 54,000 and 52,000 whereas the other enzymes converted the PCI to a product with Mr = 54,000. PCI did not detectably inhibit alpha-factor XIIa or plasmin. Kinetic studies using PCI yielded the following second-order rate constants for inhibition of human APC, 2c-uPA, 2c-tPA, thrombin, factor Xa, kallikrein and factor XIa respectively: 0.65 x 10(4), 0.22 x 10(4), 0.08 x 10(4), 0.61 x 10(4), 2.01 x 10(4), 6.50 x 10(4), and 9.03 x 10(4) M-1s-1 in the absence of heparin and 1.58 x 10(6), 0.43 x 10(6), 0.03 x 10(6), 0.52 x 10(6), 0.09 x 10(6), 0.18 x 10(6) and 0.74 x 10(6) M-1s-1 in the presence of optimal concentrations of heparin. The rate constants for the inhibition of factor XIa and 2c-uPA by PCI suggest a possible role of PCI in the physiologic regulation of these enzymes. The second order rate constants for inhibition of bovine APC and Gla-domainless bovine APC by human PCI were 0.61 x 10(4) and 0.26 x 10(4) M-1s-1 in the absence of heparin and 0.54 x 10(6) and 0.71 x 10(6) M-1s-1 in the presence of heparin, respectively. Calcium ions (0.05 to 4 mM) did not affect these rate constants. The results obtained with normal and Gla-domainless APC indicate that the Gla domain of APC is not required for inactivation by PGI and is not essential for the heparin stimulation of this reaction.
...
PMID:Purification and characterization of plasma protein C inhibitor. 255 Oct 64

We studied the effects of FR-860 on coagulative and fibrinolytic activities in human plasma compared to conventional unfractionated heparin (UF-heparin). Both FR-860 and UF-heparin dose-dependently prolonged the recalcification time, activated partial thromboplastin time, prothrombin time, factor Xa (F.Xa) clotting time and thrombin time. These effects of FR-860 were weaker than that of UF-heparin. FR-860 showed equipotent efficacy on the anti-F.Xa activity, and weak antithrombin activity compared to UF-heparin. FR-860 had no effects on the activity of ATIII and fibrinolytic activity. UF-heparin shortened the urokinase-activated euglobulin lysis time and showed antiplasmin activity, but did not influence the activities of ATIII, plasminogen and alpha 2-plasmin inhibitor. UF-heparin decreased the fibrinogen level at higher doses. These efficacies of FR-860 were weaker than that of UF-heparin. These results suggest that FR-860 is more efficient and lower in bleeding risk than UF-heparin in clinical use.
...
PMID:[Effects of low molecular weight heparin (FR-860) on coagulative and fibrinolytic activities]. 261 5

Thrombotic occlusion is a frequent complication associated with the use of central venous catheters. The purpose of this study was to evaluate the efficacy of a continuous infusion of low-dose urokinase (200 U/kg/h) in clearing catheters that had not cleared after two bolus doses of urokinase in a pediatric oncology population. Fifty-eight incidents of catheter-related occlusions (49 Hickman-type catheters/nine implantable ports) as documented by radiographic dye study occurred in 227 pediatric oncology patients with 254 central venous catheters during a 1-year period. Fourteen of 58 catheters failed to clear after two bolus instillations of urokinase (5,000 U and 10,000 U). Thirteen catheters were treated for 24 hours with urokinase, 200 U/kg/h, and one catheter with urokinase, 100 U/kg/h for 24 hours. Twelve catheters were used for study. Coagulation studies were monitored preinfusion, 12 hours into the infusion, and postinfusion. Patency was reestablished in 11/12 catheters (92%) with a mean infusion time of 28.7 hours. No coagulation abnormalities or clinical bleeding associated with the urokinase infusion occurred. Only one patient exhibited a prolonged partial thromboplastin time (greater than 150 seconds); this was associated with a heparin effect. These data indicate that low-dose urokinase may be a safe and effective means to clear occluded central venous catheters in children.
...
PMID:Continuous infusion of low-dose urokinase in the treatment of central venous catheter thrombosis in infants and children. 265 25

Glutamylglycinylarginyl chloromethyl ketone, tyrosylglycinylarginyl chloromethyl ketone, and phenylalanylprolylarginyl chloromethyl ketone have been labeled at their amino termini using fluorescein, rhodamine-X, lissamine-rhodamine, pyrene, and the 1,5-, 2,5-, and 2,6-dimethylaminonaphthalene-1-sulfonyl moieties. These peptidyl chloromethyl ketones have also been modified by incorporation of biotin and epsilon-amino caproyl biotin. The ability of these various chloromethyl ketones to be incorporated into a collection of zymogen-enzyme pairs has been evaluated using a variety of coagulation and fibrinolytic proteins. All labeled chloromethyl ketones were efficiently incorporated into the proteases tested, with the exception of urokinase which was refractory to inhibition by phenylalanylprolylarginyl chloromethyl ketone derivatives. No modification of any zymogen species was observed even under conditions designed to detect minimal reactivity. When enzymes were modified using chloromethyl ketones labeled with epsilon-amino caproyl biotin, the modified proteins readily reacted with avidin under a variety of different conditions. The observed reactivity with avidin was used in enzyme "blotting" following electrophoretic resolution of polypeptide chains and to remove active enzyme present in enzyme-zymogen mixtures. These reagents have been used to evaluate the potential for active site expression by the single-chain human factor VII molecule. Studies conducted with tissue factor, phospholipids, and calcium using factor X as substrate demonstrate that no activity can be obtained without initial activation of either factor X to factor Xa or factor VII to factor VIIa by an external source. We thus conclude that factor VII is a true zymogen, inert in the blood clotting process prior to its cleavage to factor VIIa.
...
PMID:Zymogen/enzyme discrimination using peptide chloromethyl ketones. 270 77

The inhibitory effect of the clinically used p-carbethoxyphenyl ester of epsilon-guanidino-caproic acid methanesulphonate (epsilon-GCA-CEP) on the catalytic properties of human LYS77-plasmin (EC 3.4.21.7), bovine factor Xa (EC 3.4.21.6), bovine alpha-thrombin (EC 3.4.21.5), ancrod (EC 3.4.21.28), crotalase (EC 3.4.21.30), bovine beta-trypsin (EC 3.4.21.4), porcine pancreatic beta-kallikrein-B (EC 3.4.21.35), human urinary kallikrein (EC 3.4.21.35) and the Mr 54,000 species of human urokinase (EC 3.4.21.31) was investigated (between pH 2.0 and 8.5, I = 0.1 M; T = 21 +/- 0.5 degrees C), and analyzed in parallel with that of the homologous derivative p-carbethoxyphenyl epsilon-amino-caproate hydro chloride (epsilon-ACA-CEP). On lowering the pH from 5.5 to 3.0, values of the apparent dissociation inhibition constant (Ki) for epsilon-GCA-CEP and epsilon-ACA-CEP interaction with the serine proteinases considered increase, reflecting the acidic pK-shift upon inhibitor binding of a single ionizing group. Over the whole pH range explored, (i) epsilon-GCA-CEP interacts with bovine factor Xa and bovine alpha-thrombin with an higher affinity than that observed for epsilon-ACA-CEP binding; (ii) both inhibitors associate to bovine beta-trypsin with the same affinity; and (iii) epsilon-ACA-CEP inhibits human Lys77-plasmin and the Mr 54,000 species of human urokinase with an higher affinity than that reported for epsilon-GCA-CEP association, thus reflecting the known enzyme primary specificity properties. However, the affinity of epsilon-ACA-CEP for ancrod, crotalase, porcine pancreatic beta-kallikrein-B and human urinary kallikrein, all of which preferably bind arginyl rather than lysyl side chains at the primary position of substrates and/or inhibitors, is paradoxically higher than that displayed by epsilon-GCA-CEP. By considering the amino acid sequences, the X-ray three-dimensional structures and/or the computer-generated molecular models of serine proteinase: inhibitor adducts, the observed binding behaviour of epsilon-GCA-CEP and epsilon-ACA-CEP to the enzymes considered has been related to the inferred stereochemistry of proteinase: inhibitor contact region(s).
...
PMID:Inhibition of serine proteinases by p-carbethoxyphenyl esters of epsilon-guanidino- and epsilon-amino caproic acid: thermodynamic and molecular modeling study. 272 72

From May 1958 to May 1987, 428 upper extremities were replanted, with an overall survival rate of 87.4 percent. With the aim of increasing the survival rate a new method was tried. Unlike conventional continuous intravenous infusion, a Teflon catheter (28 gauge) was inserted into the proximal main artery of the anastomosed artery, and a daily dose of 80 ml comprising 240,000 U of urokinase, 40 micrograms of prostaglandin E1, 10,000 U (maximum) of heparin, and low molecular weight dextran was administered by means of continuous infusion for the 10 consecutive days, during which arterial thrombosis is likely to occur. Thirteen cases (replantations and damaged digital arteries) survived without any re-operation for arterial thrombus. There were statistically significant differences (p less than 0.025) in platelet count, fibrinogen, and AT III preoperatively and three days postoperatively. There were also statistically significant differences (p less than 0.05) in prothrombin time, partial thromboplastin time, and clotting time between pre-operative measurements and those taken four and 15 hr postoperative, but those data remained within normal range. No abnormalities were present in the arteries through which the catheter was inserted, as validated by postoperative digital subtraction angiography.
...
PMID:Continuous local intra-arterial infusion of anticoagulants for digit replantation and treatment of damaged arteries. 272 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---