Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of hemofiltration on the number of platelets and on coagulation factors was investigated in patients with chronic renal insufficiency. These investigations were done on 12 patients during 22 treatments with hemofiltration. Blood samples were taken before hemofiltration, 10, 30 and 120 minutes after the beginning of the treatment and at the end of hemofiltration. In comparison to the original values we found a loss of platelets, a small decrease in the concentration of fibrinogen and a small increase in the fibrin monomer complex, plasminogen, antithrombin III, alpha1-antitrypsin and in alpha2-macroglobulin. The thrombin time, the partial thromboplastin time and Quick's test showed that the blood of these patients contained sufficient hepatin. Use of fibrin plates (Astrup) showed no signs of fibrinolytic activity. Compared to the results, which were obtained some years ago during hemodialysis, we found a smaller extent of alterations of blood coagulation factors and number of platelets.
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PMID:Alterations of clotting factors and platelets during hemofiltration. 7 95

Prekallikrein, plasminogen and prothrombin of human blood plasma have been separately activated by caolin streptokinase and thromboplastin. By measuring the TAME-esterase (N-d Tozy-L-arginine methyl ester) activity of each enzyme and its changes in the course of plasma incubation with the activator, it was possible to estimate the values of precursors of kallikrein, plasmin, thrombin and their inhibitors. Evidence is given that under conditions described the activation is specific of each enzyme and does not affect the level of the two other percursors. The method has been developed in two modifications, permitting to obtain the value of seven parameters in 0.4--0.7 ml of blood plasma.
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PMID:[Method of simultaneous determination of kallikrein, plasmin and thrombin precursors and inhibitors in human blood plasma]. 13 76

Rates of hydrolysis of the newly developed peptide chromogenic substrates S-2160 (N-Bz-Phe-Val-Arg-pNA, HCl), S-2238 (H-D-Phe-Pip-Arg-pNA, 2HCl), S-2222 (N-Bz-Ile-Glu-Gly-Arg-pNA, HCl), and S-2251 (H-D-Val-Leu-Lys-pNA, 2HCl) from AB Kabi Peptide Research and Chromozym TH (Z-Gly-Pro-Arg-pNA, HCl) from Pentapharm Limited were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha thrombin, and bovine factor Xa. S-2160, S-2238, and Chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All 3 substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific, being resistant to the clotting enzymes thrombin and Xa. S-2251 exhibits even greater sensitivity to the SK-plasmin complex than to plasmin. In addition, the substrate Chromozym PK (N-Bz-Pro-Phe-Arg-pNA, HCl) was evaluated and found to be relatively specific for plasma kallikrein. Assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed. Synthetic peptides mimicking amino acid sequences adjacent to proteolytic activation cleavage of plasma serine protease precursors appear to be sensitive and relatively specific tools applicable to kinetical and clinical studies of these enzymes and their inhibitors.
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PMID:Serine protease specificity for peptide chromogenic substrates. 14 72

Rates of hydrolysis of the newly developed peptide chromogenic substrates S-2160, S-2238, S-2222 and S-2251 and Chromozym TH were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha-thrombin, and bovine factor Xa. S-2160, S-2238, and chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All three substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to factor Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific. In addition, the substrate Chromozym PK was evaluated and found to be relatively specific for plasma kallikrein. Clinically useful assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed.
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PMID:Sensitivity and specificity of plasma serine protease chromogenic substrates. 14 51

Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur.
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PMID:Hemostatic factors in primary hepatocellular cancer. 19 99

A study has been made of 31 patients with coronary heart disease where diagnosis had been clearly ascertained both from a clinical and strumental point of view. All patients had undergone aorto-coronary by-pass surgery. The controls of the parameters under observation (whole-blood and plasmatic viscosity, hematocrit, fibrinogen, euglobulin lysis, T protothrombin, T of partial thromboplastin, thromboelastogram antithrombin III, plasminogen, alfa2-macroglobulin and fractions C'3c, C'3c, C'4 of the complement) were carried out as follows: basic sample taken, I control (8th-10th day), II control (15th-20th day), III control (45th-50th day), IV control (85th-90th day) after surgical operation. A global examination of our results showed significant changes in the rheologic coagulative and fibrinolytic parameters after an aorto-coronary surgical operation. The slight tendency toward hypercoagulability met with in the basic blood sample (slight increase of whole-blood viscosity, hyperfibrinogenemy, inhibition of fibrinolytic activity) does not change significantly after surgical operation. This seems to indicate that the coronary by-pass does not in any way alter the evolution of arteriosclerosis.
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PMID:[Rheologic, coagulative parameters and study of fibrinolysis in patients with coronary heart disease before and after aorto-coronary by-pass (author's transl)]. 30 20

The antiflammatory drug indomethacin, an inhibitor of prostaglandin synthesis, prevents the generalized Shwartzman reaction produced in rabbits by two intravenous injections of bacterial endotoxin. Indomethacin has this effect if given before the first but not the second injection of endotoxin. Measurements of circulating white blood cells, platelets, partial thromboplastin time, prothrombin time, fibrinogen, plasminogen, and soluble fibrin were made at several times after either the first or second injection of endotoxin treated and nontreated rabbits. Four hours after the first injection of endotoxin, leukopenia and thrombocytopenia were somewhat greater in treated rabbits and the prolongation of the activated partial thromboplastin time was shortened. Twenty-one hours after injection of endotoxin, leukocytosis and elevation of plasma fibrinogen were not as great in treated animals. Four hours following the second injection of endotoxin a decrease in fibrinogen, prolongation of the prothrombin time, and the elaboration of soluble fibrin were consistently found in rabbits with the generalized Shwartzman reaction. In treated rabbits, none of these changes occurred. Indomethacin prevents the generalized Shwartzman reaction by preventing the development of the prepared state in this endotoxin model.
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PMID:The effects of indomethacin on the generalized shwartzman reaction. 33 45

Plasma levels of antithrombin III, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor, as well as those of various clotting, complement and other plasma factors, were significantly decreased in 18 patients suffering from hyperdynamic septic shock. A similar statistically significant reduction of the concentrations of several plasma factors (prothrombin and antithrombin III, plasminogen and alpha 2-plasmin inhibitor, complement factor C3 and clotting factor XIII) was observed in experimental endotoxaemia. In this model the reduction in the plasma levels of these factors was considerably diminished by the intravenous injection of a granulocytic elastase--cathepsin G inhibitor of lower molecular weight from soybeans. The results of both studies indicate that consumption of plasma factors in the course of Gram-negative sepsis proceeds not only via the classical routes (by activation of the clotting, fibrinolytic and complement cascades by system-specific proteinases such as thrombokinase or the plasminogen activator) but also to an appreciable degree of unspecific degradation of plasma factors by neutral proteinases such as elastase and cathepsin G. The endotoxin-induced release of both sorts of proteinases, the system-specific ones and the unspecific lysosomal proteinases from leucocytes and other cells, is likely to be mainly responsible for the consumption of antithrombin III and alpha-2-macroglobulin via complex formation (followed by elimination of the complexes) and the increased turnover of the inter-alpha-trypsin inhibitor as observed in the clinical study. The therapeutic use of an exogenous elastase--cathepsin G inhibitor in the experimental model was stimulated by the observation that human mucous secretions contain and acid-stable inhibitor of the neutral granulocytic proteinases, called HUSI-I or antileucoproteinase. This inhibitor protects mucous membranes and soluble proteins against proteolytic attack by leucocytic proteinases released in the course of a local inflammatory response. Preliminary results indicate that HUSI-I, which is produced by the epithelial cells of mucous membranes, does not belong to any known structural type of acid-stable proteinase inhibitor. The search for other candidates suitable for medication in humans led to the discovery of a potent elastase--cathepsin G inhibitor, called eglin, in the leech Hirudo medicinalis. This acid-stable inhibitor with a molecular weight close to 8100 has an unusual structural property in that the structure of the molecule is not stabilized by any disulphide bridge.
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PMID:Proteinase inhibitors in severe inflammatory processes (septic shock and experimental endotoxaemia): biochemical, pathophysiological and therapeutic aspects. 39 95

In the present study, the coagulative and the fibrinolytic faculties of the Japanese monkey (Macaca fuscata) were investigated and compared with those of the human. Regarding the coagulative faculty, the plasmic fibrinogen level, prothrombin times, and partial thromboplastin times of the Japanese monkey were similar to those of the human, but the antithrombin level in the monkey was higher than that in the human. Regarding the fibrinolytic faculty, the simian plasminogen level was significantly higher than the human, but the simian, plasma clot and the euglobulin clot lysis times were extremely prolonged, which means that the Japanese monkey has a great fibrinolytic potential, but that it is difficult to activate. In addition, the human and simian reactivities of plasminogen to streptokinase were also investigated and compared.
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PMID:Comparative studies of coagulative and fibrinolytic faculties between the Japanese monkey and the human. 40 88

The levels of components of the coagulation mechanism and fibrinolytic system in 20 hyperthyroid patients and 9 hypothyroid patients were compared with those of 20 euthyroid control subjects. The mean levels of fibrinolytic activity and plasminogen were significantly reduced in the hyperthyroid patients while mean levels of alpha1-antitrypsin and C1 inactivator were increased. Patients with hypothyroidism had significantly increased levels of fibrinolytic activity and alpha2-macroglobulin, a prolonged partial thromboplastin time, and reduced levels of factor XII and antithrombin III.
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PMID:Coagulation and fibrinolysis in thyroid disease. 41 38


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