Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil-activating peptide 2 (NAP-2), corresponding to platelet basic protein fragment 25-94, was prepared by chymotryptic digestion of its precursors, low affinity platelet factor 4 or beta-thromboglobulin, followed by purification by high performance liquid chromatography. NAP-2 (0.1-1.5 microns) caused the release of human granulocyte elastase from cytochalasin B-treated neutrophils in a dose-dependent manner. In the same system, beta-thromboglobulin, human platelet factor 4, S-pyridylethyl NAP-2, and platelet basic protein C-terminal fragment (77-94) were inactive, whereas platelet basic protein fragment 22-89 had low, but significant, activity. Sensitive immunological identification of NAP-2 based on nonequilibrium isoelectric focusing and immunoblotting is described.
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PMID:Isolation, characterization, and immunological detection of neutrophil-activating peptide 2: a proteolytic degradation product of platelet basic protein. 153 40

The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta-thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD.
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PMID:Clinical effects of a polyethylene glycol grafted cellulose membrane on thrombogenicity and biocompatibility during hemodialysis. 225 72

Performance studies and investigations of the biocompatibility of a new hemodialysis membrane were conducted in patients being chronically hemodialyzed. The investigated polycarbonate membrane revealed a very satisfying performance with regard to clearance values and the ultrafiltration rate. The biocompatibility studies showed a significant leukopenia and an increase of C5a, platelet factor 4 and granulocyte elastase. Thrombocytes and C3d remained unchanged. Long-term studies have to confirm whether or not the new membrane is more biocompatible, a suggestion which could be advanced, as no febrile episodes were observed during any treatment, a finding which is not typical for Cuprophan hemodialysis.
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PMID:Performance and biocompatibility of a new hemodialysis membrane. 363 11

The purpose of this study was to determine if human platelet factor 4 (PF4) stimulates human leukocyte elastase (HLE) against lung elastin. Lung elastin was purified from hamster lungs and tritiated by reduction with NaB3H4. We found that HLE activity against this substrate is increased by concentrations of PF4 as low as 1.6 microgram/ml, and that this stimulation increased linearly with additional PF4. Lungs removed from hamsters and inflated with solutions containing buffer alone, low dose HLE, HLE plus PF4, or PF4 alone were incubated for 2 h at 37 degrees C. Whereas low-dose HLE failed to lower lung elastin when compared to control animals, HLE stimulated by PF4 lowered lung elastin by 20%. PF4 alone had no effect. Furthermore, low-dose HLE failed to alter the mechanical properties of hamster lungs as measured by pressure-volume curves in saline, although there was a significant loss of lung elasticity in the mid- and high-lung volume ranges in lungs treated with HLE and PF4. Morphologic studies revealed that low dose HLE resulted in a minimal emphysemalike lesion whereas HlE plus PF4 caused a significantly more severe lesion. PF4 is capable of stimulating HLE against lung elastin, and this effect may have a role in the pathogenesis of emphysema.
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PMID:Stimulation of human leukocyte elastase by platelet factor 4. Physiologic, morphologic, and biochemical effects on hamster lungs in vitro. 690 73

Although activation of formed blood elements during cardiopulmonary bypass has been examined, its presumed procoagulant role has not been identified or quantified. We evaluated the effects of iloprost, an inhibitor of platelet and leukocyte function, on subclinical coagulation during simulated extracorporeal circulation. We determined that a heparin dose of 1 U/ml prevented clot formation in this model, but resulted in elevated plasma levels of fibrinopeptide A, the first cleavage product of fibrinogen. Human blood was recirculated with 1 U/ml heparin using a roller pump and pediatric reversed hollow fiber oxygenator (0.8 m2) for 2 hr at 37 degrees C. Iloprost (1 ng/ml, n = 5) reduced platelet adhesion, with platelet counts of 78 +/- 7% (mean +/- SEM) of baseline during 2 hr of simulated extracorporeal circulation, compared to 36 +/- 6% in control circuits (CONT: n = 6, P < 0.05). Plasma levels of platelet factor 4 and beta-thromboglobulin were also reduced by iloprost (486 +/- 116 ng/ml vs CONT, 2933 +/- 275 ng/ml, P < 0.05, and 938 +/- 274 ng/ml vs CONT, 5700 +/- 1109 ng/ml, P < 0.05, respectively). Circulating leukocyte counts were maintained in iloprost circuits (6.4 +/- 0.6 x 10(3)/mm3 vs CONT, 4.2 +/- 0.3 x 10(3)/mm3, P < 0.05), and neutrophil elastase levels rose to only 0.4 +/- 0.1 ng/ml in iloprost circuits, compared to 0.8 +/- 0.1 ng/ml in CONT (P < 0.05). Finally, iloprost treatment reduced fibrinopeptide A levels to 102 +/- 28 ng/ml (CONT, 793 +/- 337 ng/ml, P < 0.05) after 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iloprost reduces procoagulant activity in the extracorporeal circuit. 769 41

The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant platelet factor 4 normalized thrombin times and activated partial thromboplastin times within minutes of injection, but protamine did not. Neither drug altered bleeding times. Recombinant platelet factor 4 caused a species-specific leukopenia in baboons and significantly increased activated complement protein 3 (C3a) more than protamine. However, the increase in plasma C3a was small and neither drug caused a significant increase in plasma neutrophil elastase-alpha 1 proteinase inhibitor complex. We conclude that recombinant platelet factor 4 is effective and safe in baboons, does not have an anticoagulant effect with excess concentration, and reverses in vivo heparin more rapidly than protamine. The data support progression to a clinical trial.
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PMID:Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass. 771 25

The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin-coated oxygenator group (Group H), a heparin-coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14.5 +/- 4.7 x 10(4)/microliters in Group H and 13.8 +/- 8.7 x 10(4)/microliters in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 +/- 40 ng/ml) than in Group C (297 +/- 131 ng/ml) after protamine administration. Thromboxane-B2 (TXB2) rose during CPB in both groups; however, there were significantly different levels of TXB2 between the 2 groups at 60 min after CPB (293 +/- 258 pg/ml in Group H versus 408 +/- 120 pg/ml in Group C) and after protamine administration (259 +/- 122 pg/ml in Group H versus 709 +/- 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post-CPB than those of Group C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biocompatibility of heparin-coated membrane oxygenator during cardiopulmonary bypass. 788 27

This study describes the present knowledge regarding the clinical application of argatroban, a direct competitive thrombin inhibitor for heparin-intolerant patients, including those with congenital and acquired antithrombin III deficiencies, those with heparin-induced thrombocytopenia, and those with high levels of polymorphonuclear granulocyte elastase. These patients are often associated with intracircuit clot formation with heparin anticoagulation during extracorporeal circulation. Therefore, argatroban may be chosen as one of the alternate anticoagulants. Because the anticoagulant effect of argatroban is reflected in the prolongation of activated thromboplastin time, monitoring is easy, similar to that for heparin. Because argatroban has a fast acting anticoagulant effect without any cofactors such as antithrombin III, this drug is a favorable anticoagulant for heparin-intolerant patients with antithrombin III deficiencies requiring extracorporeal circulation. In adverse reactions to heparin, heparin acts as an antigen after complexing with platelet factor 4, which leads to life-threatening heparin-induced thrombocytopenia. As argatroban prevents heparin-induced platelet aggregation, it is effective for use as a therapeutic anticoagulant. In other clinical applications, heparin decreases antithrombin activity and causes intracircuit clot formation during extracorporeal circulation when the polymorphonuclear granulocyte elastase level is very high. The antithrombin activity shows less decrease when argatroban is substituted for heparin. These findings indicate that argatroban is a useful alternative anticoagulant in these heparin-intolerant patients.
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PMID:Application of argatroban, direct thrombin inhibitor, in heparin-intolerant patients requiring extracorporeal circulation. 928 75

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.
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PMID:Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits. 980 72