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排序方式: 共有604条查询结果,搜索用时 15 毫秒
41.
42.
Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model 总被引:1,自引:0,他引:1
J M Walenga M Bakhos H L Messmore J Fareed R Pifarre 《The Annals of thoracic surgery》1991,51(2):271-277
Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin. 相似文献
43.
J Fareed J M Walenga L G Svendsen E W Bermes 《Seminars in thrombosis and hemostasis》1986,12(4):310-317
Since the introduction of synthetic peptide substrates for thrombin, many amidolytic methods for the determination of AT III, heparin cofactor II, prothrombin, thrombin, platelet factor 4, and absolute levels of heparin have been proposed. All of these methods utilize thrombin that has been standardized in coagulant assays using either fibrinogen (human or bovine) or citrated plasma substrates. These thrombin preparations may contain noncoagulant forms of thrombin, prothrombin fragments, and other serine protease enzymes. Impurities other than variant forms of thrombin in commercial preparations may interact with antithrombin and other reagents altering the results of an assay. Similarly, the noncoagulant forms of thrombin contribute to amidolytic but not coagulant activity. If these parameters are not properly controlled, the assays based on amidolysis are seriously affected. Our studies on the amidolytic and coagulant properties of commercial thrombins suggest that, although these preparations are assigned their potency in NIH units, they vary greatly and do not truly exhibit the same potency as designated in the coagulant assays. In addition, these thrombin preparations show wide variations in their amidolytic actions toward synthetic chromogenic and fluorogenic peptide substrates. We propose that thrombin preparations for chromogenic and fluorogenic peptide assays should be standardized in terms of their amidolytic activity under defined conditions. In addition, further studies should be conducted to prove their efficacy in providing reliable diagnostic information in clinical laboratory assays. 相似文献
44.
Daniel Dansdill Pegge M. Halandras Joshua Beverly Walter Jeske Debra Hoppensteadt Martin Emanuele Jawed Fareed Jae S. Cho 《Journal of vascular surgery》2018,67(1):294-299
Objective
Poloxamer-188 is a synthetic, organic compound that acts by binding hydrophobic pockets on damaged lipid bilayers in the circulation. P-188 reduces blood viscosity and confers anti-inflammatory and cytoprotective effects. Vepoloxamer (Mast Therapeutics, San Diego, Calif) is a purified version of this compound that has limited side effects. The aim of this study was to investigate drug interactions between vepoloxamer and heparin and tissue plasminogen activator (tPA).Methods
An experimental rat tail transection model was used to study vepoloxamer's interaction with heparin. Sprague-Dawley rats were divided into saline (1 mL/kg; group 1) or vepoloxamer (25 mg/kg; group 2) treatment groups. The rats were then subjected to saline (n = 6), low-dose heparin (125 μg/kg; n = 6), or high-dose heparin (250 μg/kg; n = 6). After 5 minutes, the distal 2 mm of the tail was transected, and time to clot formation was measured as bleeding time. A rat internal jugular vein thrombosis model was used to assess vepoloxamer's interaction with tPA. Sprague-Dawley rats were divided into saline (1 mL/kg; group 1) or vepoloxamer (25 mg/kg; group 2) treatment groups. After internal jugular vein thrombosis, rats were treated with saline (n = 6), systemic low-dose tPA (0.5 mg/kg; n = 6), or systemic high-dose tPA (1.0 mg/kg; n = 6). Clot lysis was assessed using an ultrasound Doppler probe to detect blood flow. No flow up to 15 minutes was recorded as no lysis.Results
Interaction with heparin: Vepoloxamer by itself, without any heparin, increased tail bleeding time (10.3 vs 7.1 minutes; P = .001). Effects of heparin on tail bleeding time were enhanced by vepoloxamer at low dose (14.2 vs 6.2 minutes; P < .001). At high-dose heparin, vepoloxamer did not prolong bleeding time (17.8 vs 17.0 minutes). Interaction with tPA: No rat exhibited spontaneous clot lysis with either saline or vepoloxamer. The effect of tPA was facilitated by vepoloxamer at low dose, as more rats showed clot lysis (4/6 [66%]) compared with tPA alone, which showed no clot lysis (0/6), although statistical significance was not reached (P = .06). At high-dose tPA, vepoloxamer had no additional effects on clot lysis (5/6 [83% ] vs 4/6 [66%]).Conclusions
Vepoloxamer alone modestly increased bleeding time. Vepoloxamer also increased bleeding time in rats treated with low-dose heparin but not with high-dose heparin. Vepoloxamer potentiated clot lysis in the setting of low-dose tPA. 相似文献45.
Eric C. Bourekas Andrew Slivka Rajul Shah Yousef Mohammad H. Wayne Slone Dimitris T. Kehagias Jose Suarez Jeffrey Sunshine Osama O. Zaidat Robert Tarr Dennis M. Landis M. Fareed K. Suri Adnan I. Qureshi 《Neurocritical care》2009,11(2):217-222
Background and Purpose
The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial showed improved outcomes in patients with proximal middle cerebral artery (MCA) occlusions treated with intra-arterial (IA) thrombolysis within 6 h of stroke onset. We analyzed outcomes of patients with proximal MCA occlusions treated within 3 h of stroke onset in order to determine the influence of time-to-treatment on clinical and angiographic outcomes in patients receiving IA thrombolysis.Methods
Thirty-five patients from three academic institutions with angiographically demonstrated proximal MCA occlusions were treated with IA thrombolytics within 3 h of stroke onset. Outcome measures included outcomes at 30–90 day follow-up, recanalization rates, incidence of symptomatic intracranial hemorrhage, and mortality in the first 90 days. The endpoints were compared to the IA treated and control groups of the PROACT II trial.Results
The median admission National Institutes of Health Stroke Scale (NIHSS) score was 16 (range 4–24). The mean time to initiation of treatment was 106 min (range 10–180 min). Sixty-six percent of patients treated, had a modified Rankin Scale (mRS) score of 2 or less at 1–3 month follow-up compared to 40% in the PROACT II trial. The recanalization rate was 77% (versus 66% in PROACT II). The symptomatic intracranial hemorrhage rate was 11% (versus 10% in PROACT II) and the mortality rate was 23% (versus 25% in PROACT II).Conclusion
Time-to-treatment is just as important in IA thrombolysis as it is in IV thrombolysis, both for improving clinical outcomes and recanalization rates as well. 相似文献46.
47.
48.
Boyangzi Li Jeffrey G. Martin Fuming Zhang Debra Hoppensteadt Jawed Fareed 《Biochemical pharmacology》2009,78(3):292-7108
An oversulfated chondroitin sulfate (OSCS) was identified as a contaminant to pharmaceutical heparin and severe anaphylactoid reactions were ascribed to this contaminant. An examination of the biochemistry underlying both the anticoagulant activity and the toxic effects of oversulfated chondroitin sulfate was undertaken. This study demonstrates that the anticoagulant activity of this oversulfated chondroitin sulfate is primarily dependent on heparin cofactor II mediated inhibition of thrombin. Heparin and oversulfated chondroitin sulfate binding to coagulation, kinin-kallikrein and complement proteins were studied by surface plasmon resonance. While oversulfated chondroitin sulfate binds tightly to antithrombin III, unlike heparin, OSCS does not induce antithrombin III to undergo the conformational change required for its inactivation of thrombin and factor Xa. In contrast to heparin, oversulfated chondroitin sulfate tightly binds factor XIIa suggesting a biochemical mechanism for the factor XIIa-based enhancement of vasoactive bradykinin production. 相似文献
49.
50.
S Ahmad O Iqbal A Ahsan D A Hoppensteadt B E Lewis J M Walenga J Fareed 《International angiology》1999,18(3):198-205
BACKGROUND: Argatroban is a peptidomimetic inhibitor of thrombin which is in clinical trials for thrombotic complications. Clot-based assays measure the cumulative anticoagulant effect of argatroban and its metabolites(s). To monitor the absolute concentrations of argatroban, a specific HPLC method was developed. METHODS: Validation studies included normal volunteers administered with escalating doses of argatroban (ARG 102 Study), patients undergoing coronary interventional procedures (ARG 310), and patients receiving argatroban in conjuction with streptokinase for acute myocardial infarction (ARG 230). Plasma samples were extracted with acetonitrile and reconstituted in a mobile phase. UV detection was made at 333 nm. Calibratrion curves were prepared with known standards of argatroban in normal human plasma. RESULTS: The retention time for argaeroban was 6.0+/-0.5 min and the extraction efficiency was >98% (r2=0.99). In the ARG102 Study, argatroban levels were: 0.84+/-0.23 (day 1), 1.55+/-0.34 (day 2), 2.92+/-0.15 (day 3), and 3.04+/-0.49 (day 4). In the ARG310 trial, the mean argatroban levels were: 0.23+0.09 microg/ml (preinfusion), 5.77+/-0.92 microg/ml (postinfusion/intraprocedure), and 2.23+/-0.29 microg/ml (postprocedure). In the ARG 230 Study, the mean argatroban levels at 2-8 hrs were between 1.5-2.0 microg/ml. Upon completion of the infusion, a time-dependent clearance of argatroban was noted. CONCLUSIONS: Since heparinization, hemodilution and hypofibrinogenemia due to thrombolysis influence the clotting tests, absolute quantitation of argatroban by HPLC in these patients provides a more reliable means of monitoring this anticoagulant and helps in the dosage-optimization of this agent. The current HPLC method is of value in the monitoring of patients who are simultaneously administered with thrombolytic drugs. 相似文献