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)

Increased mortality due to cardiovascular disease has been described in adult patients with untreated growth hormone (GH) deficiency. GH replacement therapy has been demonstrate to improve vascular reactivity and reverses early atherosclerotic changes in GH deficient adults. The objective of this study was the assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GH deficiency and with GH replacement therapy. We studied 20 GH deficient patients, 10 men and 10 women (aged, 43.4 +/- 8.4 years) under GH replacement therapy compared with a control group matched for age and body mass index, 9 men and 16 women. All subjects, patients and controls, were life-long non-smokers, normotensive and non-diabetic. The following variables were recorded: anthropometrical and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin fragments and fibrin degradation product D-dimer that were determined by an enzyme-linked-immunosorbent assay (ELISA); IGF-I by radioimmunoassay; C-reactive protein by highly sensitive immunonephelometry; E-selectine, P-selectine, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6 and monocyte chemoattractant protein-1 by ELISA. The assessment of endothelial function in vivo was measured by Doppler. Patients with GH deficiency had higher hip/waist ratio and C-peptide and triglycerides concentrations than controls. Our results demonstrated no difference in fibrinolytic markers among patients and controls. E-selectin concentrations were higher in patients than in controls, 22.5+/-11.4 vs. 10.7+/-6.2 microg/L, p = 0.0001. P-selectin, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1 and C-reactive protein were similar in the 2 groups. Vascular reactivity and carotid intima-media thickness were also similar in patients and controls. In this study we have demonstrated in adults with GH deficiency under GH substitution elevation of E-selectin concentrations that may correlate with potential endothelial dysfunction suggesting that the protective effect of GH in these patients may be enhancing other mechanisms.
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PMID:Elevation of E-selectin concentrations may correlate with potential endothelial dysfunction in individuals with hypopituitarism during therapy with growth hormone. 1731 45

Up to 20% of patients develop venographically proven deep-vein thrombosis after elective orthopedic surgery even under the cover of heparin or low molecular weight heparin. The extent to which the chronic inflammation of osteoarthritis requiring elective orthopedic surgery alters in-vivo coagulation and whether any specific alteration influences the development of postoperative thrombosis are unknown. This study compared the concentrations of activated factor VII (FVIIa), tissue factor pathway inhibitor (TFPI), activated factor X (FXa)-TFPI, thrombin-antithrombin, and prothrombin fragment 1+2 (F1+2) in plasmas of 535 healthy individuals (ages 17-76) with those in the preoperative plasmas of 306 arthritis patients (ages 30-92) scheduled for elective knee or hip replacement surgery. C-reactive protein was also measured in the plasmas of approximately 15% of the participants. Age-adjusted concentrations of FVIIa, F1+2, and C-reactive protein were higher in patients than controls, while the concentrations of thrombin-antithrombin, TFPI and FXa-TFPI were similar. Chronic inflammation in the patients was thus associated with increased coagulation in vivo. Without compensatory increases in the concentrations of TFPI (natural inhibitor of prothrombinase), the elevated concentrations of FVIIa in the preoperative plasmas and the trauma associated with surgery may enhance the risk for developing postoperative deep-vein thrombosis.
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PMID:Altered regulation of in-vivo coagulation in orthopedic patients prior to knee or hip replacement surgery. 1741 57

To investigate thrombin activatable fibrinolysis inhibitor (TAFI) in ischemic stroke and its relationship to fibrinolysis and inflammation, we investigated 32 patients with ischemic stroke during the acute phase and after 60 days. TAFI antigen levels, global markers of hemostasis (coagulation and fibrinolysis) and inflammatory markers were measured in plasma. TAFI antigen levels were significantly elevated at admission (128%; 109-151%) and at day 1 (129%; 109-152%) compared with day 60 (108%; 91-127%; both P < 0.01) and with healthy control individuals (99%; 76-122%; P < 0.05). In parallel, fibrinolysis assessed as the overall fibrinolysis potential (OFP), part of the overall hemostatic potential assay (OHP), was decreased at all time points compared with control individuals (P < 0.01 for all) and was found to be inversely related to TAFI (r = -0.40; P = 0.0008; n = 20). The OFP and the overall coagulation potential (another part of the OHP assay), and to a lesser degree TAFI, showed significant relationships to C-reactive protein and fibrinogen. In conclusion, elevated TAFI antigen levels may be a consequence of an acute phase reaction, and together with a depressed OFP suggest impaired fibrinolysis in patients with acute ischemic stroke. The OHP method may be useful as a complement to standard hemostatic variables in evaluating hemostasis in stroke patients.
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PMID:Thrombin activatable fibrinolysis inhibitor and its relationship to fibrinolysis and inflammation during the acute and convalescent phase of ischemic stroke. 1747 79

Increased frequency of thrombosis has been observed in patients with hemoglobin E/beta-thalassemia (Hb E/beta-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, beta2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/beta-thal patients. These changes may account for the increased risk of thrombosis in these patients.
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PMID:Hemostatic and thrombotic markers in patients with hemoglobin E/beta-thalassemia disease. 1765 9

Coenzyme Q10 (CoQ10, ubiquinone) is an essential cofactor in the electron transport chain, serves as a potent antioxidant in mitochondria and lipid membranes, and is often used as a dietary supplement for a number of diseases including cardiovascular diseases. Recently, we obtained evidence that CoQ10 (Kaneka Q10) affects the expression of hundreds of human genes. To decipher the functional and regulatory connections of these genes, a literature search combined with transcription factor binding site analysis was performed using Genomatix BiblioSphere and MatInspector. This in-silico analysis revealed 17 CoQ10-inducible genes which are functionally connected by signalling pathways of G-protein coupled receptors, JAK/STAT, integrin, and beta-arrestin. Promoter analysis of these CoQ10-inducible genes showed one group of NF B-regulated genes, namely IL5, thrombin, vitronectin receptor and C-reactive protein (CRP). Furthermore, a common promoter framework containing binding sites of the transcription factor families EVI1, HOXF, HOXC, and CLOX was identified in the promoters of IL5, CRP, and vitronectin receptor. The identified CoQ10-inducible genes and pathways play an important role in inflammatory response. Since these effects are based on an in-vitro study, the effect of CoQ10 on vascular health in vivo needs to be addressed in further animal and/or human intervention studies.
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PMID:Functional connections and pathways of coenzyme Q10-inducible genes: an in-silico study. 1785 68

A survey was made of the changes in hemostasis and related inflammatory biomarkers for hormone treatments (HT) of women. Treatments included were oral and non-oral estrogens combined or not with progestogens, raloxifene, tamoxifene, tibolone and ethinylestradiol in oral contraceptives with non-androgenic progestogens. Special attention was given to dosages lower than the present standard dose and we explored how treatment variants approached a situation of minimal changes in biomarkers. For oral unopposed estrogens, dose reduction effectively reduced the changes in some hemostasis markers, but not in a specific set of anticoagulant variables (antithrombin, protein S, tissue factor pathway inhibitor, and the endogenous thrombin potential assay for resistance to activated protein C). Inflammation markers from the liver showed a dose-dependent reduction but effects were not nullified at the lowest dose tested. It was concluded that adequate reduction of estrogen dose for these effects will coincide with the dose-range of efficacy. Androgenic progestogens may be suitable for further reducing the impact of estrogens on some of the anticoagulant variables; reductions of estrogen-induced C-reactive protein increases appear possible with specific progestogens (medroxyprogesterone actate, nomegestrol acetate). For non-oral unopposed estrogens, all variables except inflammation biomarkers from the vascular wall showed minimal changes. Reduction in vascular inflammatory biomarkers, considered to mark anti-inflammatory effects, is augmented by medroxyprogesterone actate or norethisterone acetate. It was concluded that unopposed, non-oral estrogen treatment is the present best available option approaching minimal effects of treatment on biomarkers. Progestogen selection requires more data. We postulated that minimal effects on all cardiovascular biomarkers should define the HT with maximal safety for venous and arterial vascular events. The survey has identified specific biomarkers sensitive to low-dose unopposed and opposed estrogen which can be used to characterize future preparations for HT.
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PMID:Effects of hormone treatment on hemostasis variables. 1788 70

To characterize hemostatic differences imposed by 2 common cardiac surgeries, the authors studied patients undergoing coronary artery revascularization by off-pump (n = 13) or cardiopulmonary bypass on-pump (n = 26) technique. Blood samples collected to 4 days post-surgery were evaluated by flow cytometry and enzyme-linked immunosorbent assay. A significant inflammatory response occurred in both the groups after surgery shown by increased interleukin cytokines and C-reactive protein; however, levels peaked lower and hours later in the off-pump group. Platelets (P-selectin; platelet-leukocyte complexes) and leukocytes (CD11b) were activated only in on-pump patients. Thrombin generation was enhanced in both groups after surgery. Only in the on-pump patients, the thrombin-antithrombin complex, pro-thrombin fragment 1.2, and thrombomodulin (vascular integrity) decreased intraoperatively. Tissue plasminogen activator and plasminogen activator inhibitor-1 were greater in the on-pump patients. Off-pump surgery may place patients at higher risk of postoperative hypercoagulability because of normal platelet function, intraoperative thrombin generation, less fibrinolytic activity, and lack of vascular protection.
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PMID:Inflammatory and hemostatic activation in patients undergoing off-pump coronary artery bypass grafting. 1816 May 69

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. In this study, the coagulation status and biochemical and non-specific inflammatory markers in patients with MS were investigated. Plasma prothrombin time, activated partial thrombin time, fibrinogen, D-dimer, serum high sensitive C-reactive protein, homocysteine, blood urea nitrogen, creatinine, calcium, total protein, albumin, total cholesterol, vitamin B12, folate levels and erythrocyte sedimentation rate were measured in 42 patients with MS and 31 healthy subjects as a control group. There was a positive correlation between homocysteine and D-dimer levels (r=0.84, p<0.01). However, there was no significant correlation between homocysteine, vitamin B12 (r=0.18) and folate (r=0.23) levels. Serum total protein, albumin and calcium levels of MS patients were lower than the control group. There are some alterations in the coagulation and biochemical status in MS patients. These findings may contribute to better understanding of the etiopathogenesis and clinical characteristics of this disease.
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PMID:Coagulation status and biochemical and inflammatory markers in multiple sclerosis. 1825 32

Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD). Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. 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. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p < 0.05) and significant increase of both the velocity index (p < 0.001) and peak thrombin (p < 0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p < 0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD.
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PMID:Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test. 1827 89

Procoagulant state, inflammation, and endothelial dysfunction have been documented in metabolic syndrome. Endothelial dysfunction is a strong predictor of cardiovascular events. Studies on the association of thrombin-activatable fibrinolysis inhibitor and thrombosis are still controversial, but substantial evidence suggests that increased thrombin-activatable fibrinolysis inhibitor or thrombin-activatable fibrinolysis inhibits or protects against arterial thrombosis. This study aimed to assess concomitantly the effects of fenofibrate therapy on thrombin-activatable fibrinolysis inhibitor concentrations and endothelial functions in patients with metabolic syndrome. Twenty-five patients (16 women; mean age 50.4 +/- 7.0) were enrolled in the study. Plasma thrombin-activatable fibrinolysis inhibitor, C-reactive protein, and fibrinogen levels were measured before fenofibrate administration and after 8 weeks of fenofibrate treatment. Endothelial function was assessed by endothelial-dependent flow-mediated dilatation from brachial artery. Pretreatment (baseline) thrombin-activatable fibrinolysis inhibitor level was 52.3 (1.2-119.7) decreasing to 7.7 (0.9-51.2; P < 0.001) after 8 weeks of fibrate treatment. Endothelial functions, which were measured with flow-mediated dilatation, were significantly improved after treatment (mean flow-mediated dilatation was 6.76 +/- 2.21 at baseline and 10.66 +/- 1.17% after 8 week of fenofibrate treatment, P < 0.001). Fenofibrate decreases thrombin-activatable fibrinolysis inhibitor levels and improves endothelial function in metabolic syndrome and, thus, suggests a potential for protection against cardiovascular effects. Further studies are warranted to confirm the effects of fibrates on thrombin-activatable fibrinolysis inhibitor and for conclusive evidence on the association between thrombin-activatable fibrinolysis inhibitor and thrombosis.
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PMID:Fenofibrate improves endothelial function and decreases thrombin-activatable fibrinolysis inhibitor concentration in metabolic syndrome. 1846 53


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