Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.
 ...
PMID:Altered properties of the fibrin gel structure in patients with IDDM. 924 13

Twelve patients with acute pancreatitis admitted to our department between January 1993 and December 1994 were studied prospectively and classified into two groups (severe group, five patients; mild group, seven patients), according to the criteria for grading severity of acute pancreatitis proposed by the Research Committee for Intractable Diseases of the Pancreas, Japanese Ministry of Health and Welfare (1990). To evaluate markers for early estimation of the severity of acute pancreatitis, we measured serum changes in various parameters. In the severe group interleukin-6 (IL-6) levels were increased significantly 5, 24, 72, and 120 h after the onset (p < 0.01), compared with the mild group. C-reactive protein (CRP), thrombin antithrombin III, and alpha 2-plasmin inhibitor plasmin complex levels were significantly increased only at the 72-h time point. Peak values of interleukin-8 (IL-8) and soluble human E selectin were observed at 5 and 72 h, respectively, after the onset. There was a significant correlation between IL-6 at 5 h and both pancreatic secretory trypsin inhibitor (r = 0.85) and CRP (r = 0.94) at 72 h. We therefore conclude that IL-6 is a useful marker for assessment of the severity of acute pancreatitis in its early stages.
 ...
PMID:Interleukin-6 is a useful marker for early prediction of the severity of acute pancreatitis. 959 21

Disseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 +/- 0.23 g/l (mean +/- SE, n = 5; p < 0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 +/- 0.12 g/l). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 +/- 0.4 mg/l to a maximum of 33.0 +/- 7.3 at day one, which was five-fold higher (p < 0.01) than in control animals at day one (6.2 +/- 0.5 mg/l). Transient increases were observed within 6h for interleukin-6 from basal values of 6.2 +/- 1.7 ng/l to peak plasma levels of 42.9 +/- 21.4 ng/l, a value three-fold higher (p = 0.07) than in control animals (14.8 +/- 4.0 ng/l). The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.
 ...
PMID:The effect of factor Xa/phospholipid infusion on the acute phase response in baboons. 915 87

In a prospective study, the role of various hemostatic factors known to be associated with thrombotic risk was investigated in 71 patients with peripheral arterial occlusive disease (PAOD, stages II through IV, Fontaine; aged 68 +/- 13 years). Laboratory investigations were done before; 1, 24, and 48 hours after; and 3 and 6 months after percutaneous transluminal angioplasty (PTA). Thirty of 71 (42.3%) patients developed restenosis (> 50% reduction of the lumen diameter) at the site of PTA within 6 months, verified by color-coded duplex sonography. Significantly increased levels of thrombin-antithrombin III complexes (P < .01), prothrombin fragments 1 + 2 (P < .01), and D-dimers (P < .01) were found 1 hour, as well as 24 to 48 hours, after PTA. Fibrinogen (P < .01) and von Willebrand factor (P < .01) were significantly higher 48 hours after PTA. Restenotic patients as a whole had higher plasma fibrinogen (3.46 +/- 1.12 versus 2.95 +/- 0.62 g/L, P < .01) and C-reactive protein (25.4 +/- 46.7 versus 7.9 +/- 6.9 mg/L, P < .05) at baseline, as well as higher fibrinogen (P < .05) and prothrombin fragments 1 + 2 (P < .01) during months 3 to 6 after PTA. There was a nonsignificant tendency for higher values of von Willebrand factor (206 +/- 98% versus 184 +/- 100%, P = .2) at baseline in patients with restenosis, whereas tissue plasminogen activator, plasminogen activator inhibitor, coagulation screening tests, blood cell counts, and serum lipids showed no significant difference between the two groups. The relative risk for developing restenosis within 6 months while having high fibrinogen (> 2.8 g/L) or C-reactive protein at baseline was 2.80 (95% CI: 1.30-6.02, P < .01) and 1.96 (95% CI: 1.07-3.58, P < .05), respectively. Patients with critical limb ischemia (stage III/IV, Fontaine) had significantly higher fibrinogen and von Willebrand factor at repeated points of time, as well as significantly higher C-reactive protein and lower creatinine clearance at entry. In the logistic regression risk factor analysis, baseline plasma fibrinogen, C-reactive protein concentration, and the severity of the arterial disease were significantly predictive of restenosis. Our results indicate that high procoagulant factors and persistent thrombin generation of the hemostatic system might promote restenosis, particularly in patients with extended atherosclerosis. This finding suggests that new treatment strategies should be taken under consideration for patients with PAOD and PTA.
 ...
PMID:Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty. 940 13

Although expanded polytetrafluoroethylene (ePTFE) has been believed to be an inert material for vascular prosthesis, it shows less tendency of graft maturation by means of endothelialization. The aim of this study is to evaluate long-term alteration in thrombogenicity of ePTFE grafts after implantation. Serial levels of thrombin-antithrombin III complex (TAT), D-dimer, C-reactive protein (CRP), and prothrombin time (PT) were examined in 77 patients following ePTFE Y-graft implantation for up to five years. TAT showed biphasic elevation after implantation; TAT increased from 16.4+/-8.6 ng/ml to 27.4+/-10.5 ng/ml at one day, decreased to 18.5+/-4.5 ng/ml at one week, and increased again to 25.3+/-8.5 ng/ml at two weeks. Elevated TAT gradually decreased after the second peak to reach a lower level than that before surgery after six months. There was no significant difference in TAT level after six months due to the difference in diagnosis or anti-thrombotic therapy. We suggest that ePTFE grafts lose their thrombogenicity six months after implantation, after which anti-thrombotic therapy might be unnecessary.
 ...
PMID:Expanded polytetrafluoroethylene (ePTFE) vascular graft loses its thrombogenicity six months after implantation. 955 31

Activation of blood coagulation and fibrinolysis has previously been detected in stroke patients. It is unknown, however, what factors contribute to the acceleration of coagulation reactions, especially in cases where no obvious predisposing factors exist. We therefore postulated and tested the hypothesis that in such patients monocytes may trigger the pathway leading to thrombosis by expressing tissue factor (TF). TF antigen was determined in 48 patients and 40 controls by flow cytometry using an indirect immunofluorescent technique. TF antigen expression was significantly increased on monocytes in young stroke patients in both the acute (p < 0.01) and chronic (p < 0.05) phases of the disease. The TF antigen also possessed functional activity, quantitated by a one-stage clotting assay. TF expression on monocytes was not associated with an elevation in C-reactive protein values. In both acute and chronic phases, blood coagulation activation markers, e.g. the thrombin-antithrombin complex and F1 + 2 fragments, were significantly elevated. However, in the acute phase D-dimer levels were similar to those in controls and were only elevated in the chronic phase of the disease (p < 0.05). In conclusion, in cerebral ischemia TF expression on monocytes suggests enhanced activation of blood coagulation and subsequent fibrinolysis.
 ...
PMID:Monocytes express tissue factor in young patients with cerebral ischemia. 968 64

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.
 ...
PMID:Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia. 969 66

In order to evaluate whether different clinical presentations of unstable angina are associated with a different degree or pattern of activation of the hemostatic, fibrinolytic and inflammatory systems, we measured plasma levels of thrombin-antithrombin III, plasmin-alpha2- antiplasmin complexes and C-reactive protein, as markers of activation of coagulation, fibrinolysis and inflammation respectively, in two groups of patients: 7 patients with de novo unstable angina (Group 1) and 7 patients with destabilizing unstable angina (Group 2). Blood samples were taken on admission for measuring levels of C-reactive protein and during ischemic episodes at the onset of ECG changes and pain (0 min) and after 5, 15 and 60 min in order to assess the peak values of thrombin-antithrombin III and plasmin-alpha2-antiplasmin during the episode. Thrombin-antithrombin III levels in Group 1 were 1.8 microgram/l (0.3-4.15) at 0 min and increased to 17 micrograms/l (2.8-60) after 5 to 15 min (p = 0.013); conversely thrombin-antithrombin III levels in Group 2 were 2.15 microgram/l (1.4-3.8) at 0 min and raised to 4 micrograms/l (2-43) after 5 to 15 min (NS). No significant differences in both groups were observed in plasmin-alpha2-antiplasmin levels (Group 1:650 micrograms/l, ranged 492-956, at 0 min vs 670 microgram/l, range 415-977, at peak; Group 2: 480 micrograms/l, range 274-955, at 0 min vs 502 micrograms/l, range 304-1027, at peak; NS). Inversely, C-reactive protein levels on admission were 4 mg/dl (range 2-27) in Group 1, and 1 mg/dl (range 0.6-4) in Group 2 (p = 0.006). In conclusion, patients with de novo unstable angina have significantly enhanced thrombin (but not plasmin) production during spontaneous ischemic episodes than patients with destabilizing unstable angina. Furthermore, patients with de novo unstable angina have enhanced acute phase responses than patients with destabilizing unstable angina. Our data suggest that different pathogenetic mechanisms may be responsible for acute ischemic episodes in unstable angina and may explain different response to antithrombotic therapy in unstable angina patients.
 ...
PMID:[Clinical presentation of unstable angina may influence the formation of thrombin during spontaneous episodes of ischemia]. 970 80

Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.
 ...
PMID:Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis. 972 74

Multiple organ failure frequently occurs in patients with acute liver failure, and this has been associated with increased cytokine production. Treatment by hemoperfusion with an extracorporeal liver assist device (ELAD) containing human liver-derived cells was performed in 12 patients with acute liver failure. Over the first 6 h, there were significant increases in plasma tumor necrosis factor alpha (TNFalpha; from 114+/-54 pg/ml [mean+/-SEM] to 236+/-161 pg/ml, p < 0.05) and interleukin (IL)-6 (260+/-121 pg/ml to 445+/-149 pg/ml, p < 0.05) but not in interferon gamma (IFNgamma). A similar pattern with a small peak increase was observed for complement C5b-9 complex. Plasma C-reactive protein (CRP) and thrombin antithrombin (TAT) III complex showed small peaks after 24 h of ELAD hemoperfusion. No such changes were seen in 12 control patients with acute liver failure who were treated with intensive care alone. These transitory effects, without changes in blood pressure, are likely to be due to the contact of the blood with the dialyzer membrane. There was no evidence of the clearance of cytokines by the ELAD.
 ...
PMID:Plasma cytokine levels and coagulation and complement activation during use of the extracorporeal liver assist device in acute liver failure. 979 83


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