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

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the quantitative changes of hemostatic molecular markers with time during the course of disseminated intravascular coagulation (DIC) induced by endoscopic embolization using thrombin for esophageal varices in nine patients with liver cirrhosis. The plasma levels of D-dimer, a product of plasmin degradation of cross-linked fibrin, and thrombin-antithrombin-III complex (TAT) were significantly higher in patients before treatment when compared with 60 healthy individuals. The plasma levels of TAT, D-dimer, and plasmin alpha 2-plasmin inhibitor complex (PIC) increased significantly 5-15 min after thrombin injection into the varices, earlier than the changes of conventional coagulofibrinolytic factors, reached a maximum level after 180 min, and started to decline after 1 day. Although the plasma PIC level returned to normal after 7 days, both TAT and D-dimer were still above the pretreatment level. Although there was no change in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) increased significantly after 5 min. The plasma level of plasminogen activator inhibitor type 1 (PAI-1) showed only a slight elevation after treatment. We propose that the hemostatic molecular markers TAT, D-dimer, and PIC are suitable for the early diagnosis of DIC after endoscopic embolization using thrombin in patients with liver cirrhosis and that the increase of PAI-1 is too small for the regulation of fibrinolysis due to t-PA in DIC occurring in liver cirrhosis.
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PMID:Significance of hemostatic molecular markers during disseminated intravascular coagulation in patients with liver cirrhosis treated by endoscopic embolization for esophageal varices. 171 8

We performed 93 sclerotherapy sessions on liver cirrhosis patients with recurrent variceal bleedings. In each session, hypertonic glucose, thrombin and 1% polidocanol were consecutively injected into the varices, and changes in the hemostatic system were examined in relation to the symptoms observed during the treatment. Patients underwent sclerotherapy with no complaints in 62 (67%) sessions, and complained of slight symptoms of general fatigue and headache in 19 (20%). In the other 12 (13%) sessions, the procedure was discontinued due to marked manifestations of these symptoms. All symptoms were temporary and disappeared completely after the procedure. These temporary symptoms were closely related to changes in coagulation tests similar to those of disseminated intravascular coagulation, which were observed just after the treatment. Possible activation of the renal kallikrein-kinin system following injection sclerotherapy was also demonstrated.
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PMID:Manifestations of temporary symptoms during endoscopic variceal sclerotherapy using thrombin as a sclerosant. 192 Sep 57

Prelining graft material with autologous functioning endothelial cells might be one of the ultimate requirements to obtain a biocompatible surface. Accordingly, endothelial cells from stripped varicose veins were enzymatically harvested and grown on a fibronectin matrix. Proliferation was investigated in defined medium supplemented with various concentrations of endothelial cell growth supplement (ECGS) (25, up to 150 micrograms/ml) and heparin (10(-8), up to 10(-5)mol/L): optimal growth required both 150 micrograms/ml of ECGS and 10(-5)mol/L heparin. Under these conditions, cell culture achieved cell densities at a confluence of 1.2 +/- 1.1 10(5) cells/cm2 with a doubling time of 1 day. During subcultivation cultured cells consistently exhibited characteristic cobblestone morphology and immunofluorescent staining for factor VIII-related antigen, whereas prostacyclin production determined by enzyme-linked immunosorbent assay for 6-keto-prostaglandin F1 alpha reached 21.1 +/- 1.2 ng/10(6) cells after 15-minute stimulation with 1 U/ml of thrombin. Heparin-containing culture medium-endothelial cell interactions were particularly studied, and with iodine 125-heparin, binding was demonstrated with an apparent dissociation constant (Kd) of 0.36 +/- 0.04 mumol/L. A cold storage technique at -80 degrees C was sought, and freezed cells were used to coat in vitro polytetrafluoroethylene grafts. Protein-treated material allowed cell attachment and growth to a confluent monolayer as assayed by light and scanning electron microscopy. These data validate the feasibility of prelining grafts in vitro with autologous functioning endothelial cells. This approach may be useful in improving the performance of small-caliber vascular grafts according to prostacyclin production and surface-bound heparin of these cells.
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PMID:Prelining of polytetrafluoroethylene grafts with cultured human endothelial cells isolated from varicose veins. 264 96

Fifty cirrhotic Japanese patients with oesophageal varices underwent sclerotherapy in a prospective randomized trial carried out to examine the effects of human thrombin given concomitantly with the sclerosant 5 per cent ethanolamine oleate. The two groups (25 patients each) were comparable with regard to size of the oesophageal varices, and the aetiology and severity of the liver disease. Twenty-five patients, 13 and 12 in the thrombin + and - groups, respectively, had at least one episode of variceal bleeding. The remaining 25 were given prophylactic injections. There was a significantly lower rate of occurrence of bleeding from injection sites when the injection needle was removed at the initial session of sclerotherapy in the thrombin + group, where human thrombin was injected (0.2-0.3 ml, 100-150 units per injection) just before removal of the injection needle. Endoscopy at 1 week after the initial session showed a significantly (P less than 0.05) higher rate of disappearance of red colour signs on varices in the thrombin + group (96 per cent) than in the thrombin - group (72 per cent). Fibrin degradation product E-fraction (FDP-E) values increased 1 h, 1 day and 6 days after the initial session of sclerotherapy in the two groups. The rate of increase in FDP-E values 1 h after sclerotherapy was significantly larger (P less than 0.001) in the thrombin + than in the thrombin - group. There was no clinical sign of disseminated intravascular coagulation. Administration of human thrombin plus a sclerosant seems to be useful and efficacious, especially for patients with huge oesophageal varices.
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PMID:Human thrombin plus 5 per cent ethanolamine oleate injected to sclerose oesophageal varices: a prospective randomized trial. 276 8

The clearance of radioactive fibrin from the subcutaneous tissues has been measured in the rat and in the limbs of normal subjects, patients with varicose veins, and patients with lipodermatosclerosis. The animal experiments showed that the most effective way of producing a subcutaneous deposit of fibrin was by the simultaneous injection of labelled fibrinogen and thrombin. The clearance of these clots was delayed when fibrinolysis was depressed with epsilon-aminocaproic acid. Clearance of subcutaneous fibrin in man was significantly slower in the arms of patients with varicose veins and lipodermatosclerosis. Similarly clearance in the legs of patients with lipodermatosclerosis was significantly slower than that of the normal subjects and those with uncomplicated varicose veins. The clearance of fibrin from the legs of patients with lipodermatosclerosis was significantly slower than the clearance from their arms but there was no difference between arm and leg clearance in the normal subjects and those with uncomplicated varicose veins. The patients with lipodermatosclerosis had a significantly longer dilute blood clot lysis time. The inability to clear subcutaneous fibrin may be an aetological factor of lipodermatosclerosis.
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PMID:The clearance of 125I-labelled fibrin from the subcutaneous tissue of limbs with lipodermatosclerosis. 371 73

In order to assess the true incidence of haemostatic disorders in cirrhotic gastro-intestinal haemorrhage, a comparative prospective study of primary haemostasis, coagulation and fibrinolysis was carried out in 37 patients distributed into two groups: cirrhotics with gastro-oesophageal varices that had never bled (Group A = 22), and cirrhotics who had had an intestinal bleed from "ruptured" gastro-oesophageal varices (Group B = 15). Combination of thrombocytopenia (less than 100 10(9)/l) and a bleeding time greater than 8 mn was more frequent in Group B (80%) than in Group A (45%) (p = less than 0.05). On the other hand, no significant difference between the two groups was found in the activated cephalin time, thrombin time, prothrombin complex factors (II, V, VII-X), fibrinogen, antithrombin III, Factor VIII complex factors, FDP levels or plasminogen. In conclusion, these results suggest that disorders of primary haemostasis may be involved in bleeding from gastro-intestinal varices in cirrhosis. However, coagulation disorders and anomalies of fibrinolysis would not seem to play a determining role.
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PMID:[Importance of disorders of primary hemostasis in the occurrence of upper digestive hemorrhage in cirrhosis]. 633 45

The effect of long and short-term venous hypertension upon lymph fibrinogen concentrations was studied in an attempt to explain the peri-capillary deposition of fibrin reported in patients with post-phlebitic syndromes. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of rats and human volunteers was also studied. Both long- and short-term venous hypertension were found to increase fibrinogen transport across the interstitial space by more than 600%. Not only was there evidence of fibrinolytic activity in the lymph but after long-term venous hypertension alpha 2 antiplasmin activity was also detectable. Skin biopsies from the venous hypertensive ankles showed deposition of interstitial fibrin. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of the rat was found to be delayed if the rats were given epsilon amino caproic acid but it could not be increased with stanozolol. In human subjects it was found that patients with lipodermatosclerosis had delayed clot clearance and retarded blood fibrinolytic activity when compared with normal volunteers and patients with uncomplicated varicose veins. The principle cause why tall men are more subject to ulcers than short men, Dr Young conceived to be then length of the column of blood in their veins; which by its pressure, renders the legs less able to recover when hurt by any violence.
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PMID:Venous ulceration, fibrinogen and fibrinolysis. 674 38

Fifty-three patients with upper gastrointestinal bleeding and proven esophageal varices were treated by intravascular injection sclerotherapy of the varices using a mixture of ethanolamine oleate, bovine thrombin and cephalothin. An intraesophageal balloon was used to impede craniad flow during the injection. Except in three patients who failed to stop bleeding from nonvariceal lesions, sclerotherapy was 94 percent successful in controlling bleeding. The mortality rate in sclerotherapy patients with ascites was 25 percent compared with 54 to 75% reported elsewhere. There has been no rebleeding from varices after the third treatment week in patients followed up for up to 14 months.
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PMID:Injection sclerotherapy of esophageal varices using ethanolamine oleate. 697 20

The functional thrombin receptor, normally expressed by endothelial cells and platelets, is a member of the G protein-coupled, seven membrane-spanning-domain receptor family and is thought to be responsible for most, if not all, the cell stimulatory effects of thrombin. Upon binding, thrombin cleaves the receptor's N-terminal ectodomain, unmasking a new N terminus, which by itself activates the receptor. Using antibodies to different domains of the human thrombin receptor, we have localized the receptor in cultured human umbilical vein endothelial cells by indirect immunofluorescence and immunoelectron microscopy. We found the receptor expressed on the plasmalemma of cultured endothelial cells in individual units rather than in clusters, at lower concentration than, and at different sites from, thrombomodulin. We also found the receptor associated with a distinct, intracellular, transferrin receptor-containing, tubulovesicular network. The thrombin receptor-positive structure spread from the perinuclear region to the periphery of the cells, exhibiting a number of varicosities interconnected by branching tubular elements, strikingly similar to an image recently described for a continuous endosomal reticulum. Our results provide morphological evidence for the presence of the functional thrombin receptor at relative low density on the surface of cultured endothelial cells (compared to thrombomodulin) and in relatively large quantities inside the cells, associated with an endosomal compartment.
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PMID:The functional thrombin receptor is associated with the plasmalemma and a large endosomal network in cultured human umbilical vein endothelial cells. 762 1

For the first time the endoscopist has more than one option for the management of gastro-oesophageal varices. It is now feasible to select the appropriate therapy on the basis of the clinical setting. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from oesophageal varices, and could be followed two or three days later by banding ligation. Earlier obliteration of varices with this technique may offer the prospect of only two or three sessions of therapy. The availability of the tissue adhesives and thrombin as injectates for fundal gastric varices provide the option of an initial attempt at endoscopic therapy in this high risk group.
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PMID:Recent advances in the endoscopic management of variceal bleeding. 779 10


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