Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.
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PMID:Hemodialysis with defibrotide: effects on coagulation parameters. 142 6

This study investigated whether the pre-surgical plasma levels of TAT and F1 + 2 of patients undergoing major surgery for localized tumours could identify patients at higher risk of thrombosis, and how heparin prophylaxis affected in vivo coagulation after cancer surgery. We measured the pre- and post-operative levels of TAT, F1 + 2, total factor VII (FVIIt) and zymogen FVII (FVIIz) in 117 cancer patients, with and without heparin prophylaxis. The end points of this study were DVT, initially detected by 125I-fibrinogen uptake test and confirmed by ascending venography. Pre-operative [TAT] and [F1 + 2] of the cancer patients were significantly higher than those of age-matched control subjects (n = 50) (P < 0.005 and P < 0.05, respectively); pre-operative [FVII] was not significantly different. One of the 83 patients receiving prophylaxis, and 8/34 not receiving prophylaxis developed post-operative DVT. Of the parameters evaluated, only the pre-operative [TAT] > 3.5 ng/ml identified patients at higher risk for post-operative DVT. Heparin reduced plasma TAT levels and FVII consumption following surgery, suggesting that heparin modulates coagulation associated with cancer surgery. The results of this study also suggest that the pre-operative [TAT] may identify patients with higher risk for post-operative DVT.
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PMID:Preliminary study to identify cancer patients at high risk of venous thrombosis following major surgery. 791 39

Heparin has been conventionally used as an anticoagulant for medical and surgical indications. Because factor Xa is an essential component of the prothrombinase complex and leads to the generation of thrombin, its inhibition has become a focus of newer antithrombotic drug development. The in vitro anticoagulant profile of DX-9065a, a synthetic direct factor Xa inhibitor, was studied using activated clotting time assay, thrombelastography, and global clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), diluted aPTT, Heptest, Heptest-HI, dilute Russell's viper venom time (dRVVT), thrombin time, ecarin clotting time, and amidolytic anti-Xa assay. In addition, the effect of DX-9065a on platelet aggregation and inhibition of thrombin generation markers (FPA, F1+2, and TAT) were studied. The pharmacokinetic and pharmacodynamic profiles of DX-9065a were also studied in a non-human primate (Macaca mulatta) model. DX-9065a produced a concentration-dependent increase in the Hemochron celite ACT and HemoTec ACT. Clotting times of 538 +/- 19 and 401 +/- 12, respectively, were reached at a concentration of 25 microg/mL signifying that DX-9065a may be useful in interventional cardiological procedures. DX-9065a prolonged the r-time on thrombelastography. DX-9065a did not show any effect on adenosine diphosphate (ADP)-, collagen-, epinephrine-, and arachidonic acid-induced platelet aggregation at concentrations up to 10 microgram/mL. DX-9065a exhibited a concentration-dependent prolongation of the PT, aPTT, diluted aPTT, Heptest, dRVVT, and reached the clotting times of 51.6, 132, 193, 47.9, 129.9 seconds, respectively, at a final concentration of 12.5 microgram/mL; compared to a control value of 10.6, 30.2, 41.9, 14, 32.2 seconds, respectively. DX-9065a did not affect the ecarin clotting time and thrombin time at concentrations up to 12.5 microgram/mL. Because DX-9065a prolonged the dRVVT, this may impact diagnostic screening of patients with systemic lupus erythematosus.
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PMID:Global anticoagulant effects of a synthetic anti-factor Xa inhibitor (DX-9065a): implications for interventional use. 1264 18

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.
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PMID:Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass. 1266 26

Phlegmasia cerulea dolens is a devastating complication of massive deep venous thrombosis, which is clinically characterized by massive lower extremity tissue edema and subsequent arterial insufficiency. These experiments evaluated the local tissue effects of acute global venous obstruction combined with partial arterial ischemia. Experiments were performed to assess the effects of heparin on the cytokine response to simultaneous venous and partial arterial obstruction. Murine hind limbs were subjected to conditions of unilateral venous occlusion and partial tourniquet limb ischemia, which was confirmed by laser Doppler imaging (LDI). Mice underwent either hind limb venous obstruction with intravenous unfractionated heparin (200IU/kg) or intravenous saline 5min before venous occlusion. Sham-treated mice were subjected to anesthesia alone without venous occlusion. After 3hr, the mice were killed and tissue was harvested for measurement of edema (wet to dry weight ratio, W/D), muscle viability, indices of local thrombosis (thrombin-antithrombin complex [TAT]), and cytokine analysis for growth-related oncogene-1 (GRO-1) and interleukin-6 (IL-6, protein via enzyme-linked immunoassay and mRNA via reverse transcriptase polymerase chain reaction). Bleeding time and volume were documented in saline- and heparin-treated mice to confirm systemic anticoagulation. Administration of intravenous heparin resulted in a marked increase in bleeding time and volume. LDI confirmed venous obstruction and ongoing arterial inflow. Venous obstruction resulted in severe visible edema that correlated with a significantly higher W/D ratio but was not associated with a significant decrease in muscle viability. GRO-1 and IL-6 protein and mRNA levels were significantly elevated in the venous occlusion group compared to sham. Heparin therapy significantly decreased TAT3 levels but did not alter the profile of GRO-1 or IL-6 protein levels seen with venous occlusion. Venous occlusion with partial ischemia induces a unique and potent local cytokine expression. Heparin therapy did not ameliorate the cytokine response. These data indicate that heparin therapy does not modulate the cytokine response to venous obstruction.
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PMID:Effects of acute global venous obstruction and unfractionated heparin on muscle cytokine synthesis. 1864 Aug 15

Human-derived cell penetrating peptides (CPPs) have attracted much more attentions than other CPPs which are limited by their potential toxicity and immunogenicity. Previously, we identified a novel human-originated CPP (named heparin-binding domain (HBD) in this article), which derived from the C-terminus of human extracellular superoxide dismutase, and demonstrated HBD is an efficient vector for delivering exogenous drug molecules such as apoptin into HeLa cells. In this study, we found this novel CPP showed differentiated efficiency in several tested cell lines. Heparin competitive inhibition experiment and heparanase pre-incubation experiment showed cell surface polysaccharides play an important role for the transmembrane transport. The results of endocytosis inhibitors suggested that HBD penetrates the cell membrane via a direct translocation, which is different from that of TAT, a classical clathrin-mediated endocytosis. HBD could deliver up to 90 kD protein cargoes into cells. Different conjugated modes with cargo molecules greatly affect their translocation efficiency. HBD also showed significant nuclear transport capacity when it was incubated with HeLa cells. Furthermore, the core region for HBD possessing membrane-penetrating ability was identified by deletion analyses. These results would be helpful for developing HBD as a new nuclear delivery tool for therapeutic biomolecules.
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PMID:Evaluating the translocation properties of a new nuclear targeted penetrating peptide using two fluorescent markers. 2560 61