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)

Alterations in haemostasis are frequently observed in children with acute lymphoblastic leukemia (ALL). It was the objective of this study to analyse age-related disturbances in coagulation and fibrinolysis parameters during the induction phase of the antileukemic treatment. Sixty-four children were classified by age into three groups (1-5, 6-10, 11-16 years), and studied during induction treatment of ALL including four weeks of dexamethasone, followed by two weeks tapering of dexamethasone during which 6,000 IU/m(2) native L-Asparaginase (total 4 doses) was administered intravenously twice weekly. Blood samples were collected immediately before each L-Asparaginase infusion to analyze procoagulant (fibrinogen, factor [F] II, FV, FVII, F IX, F X) and anticoagulant factors (antithrombin [AT], protein C, protein S), parameters of thrombin generation (F1+2, TAT) and fibrinolysis (alpha2-antiplasmin, plasminogen, PAP, D-dimer). Children were in a hypercoagulable state after four weeks of dexamethasone due to upregulation of coagulation parameters. Upregulation was highest in the two youngest age groups. During L-Asparaginase treatment the 11- to 16-year-olds showed lower values in procoagulant and, even more, in anticoagulant factor levels compared to the younger children. Activation markers of thrombin generation and fibrinolysis did not change over time during the study period. Decreased synthesis of alpha2-antiplasmin and plasminogen during L-Asparaginase treatment resulted in less potential of clot lysis by plasmin in children older than 11 years of age. In conclusion, a more severe decline of anticoagulant and fibrinolytic parameters in children between 11 and 16 years of age underline that these children are at higher risk of thrombosis during ALL induction treatment.
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PMID:L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia. 1869 Mar 55

We have shown that platinum nanoparticle species (nano-Pt) is a superoxide dismutase/catalase mimetic that scavenges superoxide and hydrogen peroxide. In Caenorhabditis elegans, nano-Pt functions as an effective antioxidant that induces an extension in lifespan and strong resistance against excessive oxidative stress. Our study with C. elegans was the first trial to use nano-Pt as a bio-active substance. However, a high concentration of nano-Pt was required for these survival effects, probably due to limited membrane permeability. Here, we show that the conjugation of nano-Pt with an HIV-1 TAT fusion protein C-terminally linked to a peptide with high affinity for platinum improves internalization, eliciting a similar level of antioxidant effects at one hundredth the concentration of unconjugated nano-Pt. This approach is a potential method to facilitate translocation of bio-active nanoparticles into living organisms and could be a model assay for estimate the effects of antioxidant in living organism.
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PMID:The effect of TAT conjugated platinum nanoparticles on lifespan in a nematode Caenorhabditis elegans model. 2043 16

We have adapted the corn-trypsin inhibitor whole-blood model to include EA.hy926 as an endothelium surrogate to evaluate the vascular modulation of blood coagulation initiated by relipidated recombinant tissue factor (rTf) and a cellular Tf surrogate, lipopolysaccharide (LPS)-stimulated THP1 cells (LPS-THP-1). Compared with bare tubes, EA.hy926 with rTf decreased the rate of thrombin formation, ITS accumulation, and the production of fibrinopeptide A. These phenomena occurred with increased rates of factor Va (fVa) inactivation by cleavages at R(506) and R(306). Thus, EA.hy926 provides thrombin-dependent protein C activation and APC fVa inactivation. Comparisons of rTf with LPS-THP-1 showed that the latter gave reduced rates for TAT formation but equivalent fibrinopeptide A, and fV activation/inactivation. In the presence of EA.hy926, the reverse was obtained; with the surrogate endothelium and LPS-THP-1 the rates of TAT generation, fibrinopeptide release, and fV activation were almost doubled, whereas cleavage at R(306) was equivalent. These observations suggest cooperativity between the 2 cell surrogates. These data suggest that the use of these 2 cell lines provides a reproducible quasi-endothelial quasi-inflammatory cytokine-stimulated monocyte system that provides a method to evaluate the variations in blood phenotype against the background of stable inflammatory cell activator and a stable vascular endothelial surrogate.
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PMID:Cellular regulation of blood coagulation: a model for venous stasis. 2086 79


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