Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary recanalization rate and infarct size were compared between 2 different methods of intravenously administering recombinant tissue-type plasminogen activator (rt-PA) 41.4 mg; 1) an initial bolus dose of 30% followed by infusion of the remainder over 60 min (30% group), and an initial bolus dose of 10% followed by infusion of the remainder over 60 min (10% group). Thirty min after beginning rt-PA infusion, the coronary recanalization rate was higher in the 30% group than in the 10% group (82.9% (34/41) vs 53.7% (22/41), p < 0.01). The peak creatine kinase and peak creatine kinase-MB levels were lower in the 30% group than in the 10% group. We conclude that a higher initial bolus dose of rt-PA gives a higher rate of recanalization of the infarct-related artery at the very early phase, and probably leads to a smaller infarct size.
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PMID:Effect of the initial bolus volume of recombinant tissue-type plasminogen activator on coronary recanalization and infarct size in Japanese acute myocardial infarction patients. Kumamoto University Myocardial Infarction Study (KUMIS) Group. 855 50

Patients who cannot be reperfused after thrombolytic therapy have a high mortality rate. Noninvasive clinical markers of reperfusion have been widely studied, yet their prognostic significance remains unclear. To assess the prognostic value of commonly used noninvasive clinical markers of early reperfusion we studied 327 patients who received intravenous thrombolytic treatment (1.5 MU streptokinase in 1 hour or 100 mg alteplase in 3 hours) within 6 hours of acute infarction. Successful clinical reperfusion (SCR) was defined as the presence of at least two of the following criteria at 2 hours after thrombolytic treatment: (1) significant relief of pain (a 5-point reduction on a 1 to 10 subjective scale), (2) > or =50% reduction of sum of ST segment elevation, and (3) abrupt initial increase of creatine kinase levels (more than twofold over the upper-normal or baseline elevated values). Clinical variables that were significantly associated by univariate analysis were tested by multivariate analysis to obtain independent predictors of 30-day mortality rate. SCR was present in 210 (64%) patients (group 1), and absent in 117 (36%) patients (group 2). The groups were similar for most baseline characteristics, although group 2 patients were slightly older (mean 60 vs 57 years, p < 0.02). Thirty-day outcomes for group 2 patients compared with group 1 patients were heart failure in 23.1% and 10.5% (p < 0.005), progression to cardiogenic shock in 12.8% and 0.5%, (p < 0.00001), and death in 16.2% and 3.8% (p < 0.0001), respectively. By multivariate analysis the Killip class at admission (p < 0.00001), the absence of SCR (p = 0.017), anterior infarct location (p = 0.021), and age (p = 0.03) were independent predictors of mortality rate, and sex (p = 0.051) had borderline significance. The absence of SCR defined a group of patients with significantly higher mortality rate (odds ratio 4.89, 95% confidence interval 2.07 to 11.57). Three simple noninvasive clinical criteria of successful reperfusion may be used to identify a group of patients with poor prognosis after thrombolytic therapy in whom alternative strategies could be applied.
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PMID:Prognostic value of clinical markers of reperfusion in patients with acute myocardial infarction treated by thrombolytic therapy. 935 29

Venoms from eight Bothrops spp. were fractionated by ion-exchange chromatography on CM-Sepharose at pH 8.0 for the purification of myotoxins. Chromatographic profiles showed differences regarding myotoxic components among these venoms. B. alternatus, B. atrox and B. jararaca venoms did not show the major basic myotoxic fractions identified in the other venoms. Polyacrylamide gel electrophoresis for basic proteins also showed distinct patterns for these toxins. In vivo, all the isolated myotoxins induced release of creatine kinase due to necrosis of muscle fibers, accompanied by polymorphonuclear cell infiltration, and edema in the mouse paw. In addition, the toxins showed cytotoxic and liposome-disrupting activities in vitro. B. jararacussu bothropstoxins-I (BthTX-I) and II (BthTX-II) were submitted to chemical modifications of: His, by 4-bromophenacyl bromide (BPB) or photooxidation by Rose Bengal (RB); Tyr, by 2-nitrobenzenesulphonyl fluoride (NBSF); and Trp, by o-nitrophenylsulphenyl chloride (NPSC). The myotoxic and cytotoxic activities of BthTX-I, a Lys49 PLA(2) homologue, after modification by BPB, RB, NBSF and NPSC, were reduced to 50%, 20%, 75%, 65% and 13%, 0.5%, 76%, 58%, respectively. However, the edema-inducing and liposome-disrupting activities were not significantly reduced by the above modifications. BPB-treated BthTX-II, an Asp49 PLA(2) homologue, lost most of its catalytic, indirect hemolytic, anticoagulant, myotoxic and cytotoxic activities. The edema-inducing and liposome-disrupting activities were reduced to 50% and 80%, respectively. Lethality caused by BthTX-I and -II was strongly reduced after treatment with BPB or RB, but only partially with NBSF or NPSC. BthTX-I and -II, both native or modified, migrated similarly in a charge-shift electrophoresis. Antibodies raised against BthTX-I or -II, B. asper Basp-II and the C-terminal 115-129 peptide from Basp-II did not show significant differences in their cross-reactivity with the modified toxins, except with RB photooxidized toxins.
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PMID:Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu. 1101 93

Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5x10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43+/-28 mmHg (mean+/-S.D.) and 40+/-26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to <90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3+/-17.5 and 40.2+/-13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.
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PMID:Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction. 1135 74

The time from admission to reperfusion in patients with acute myocardial infarction (AMI) was compared according to the type of hospital and treatment strategy. A total of 164 patients with a first AMI within 12h of onset were enrolled at one tertiary emergency center (TEC) and 6 community hospitals (CHs). The subjects were randomly assigned to receive either primary percutaneous transluminal coronary angioplasty (PTCA) (TEC-primary PTCA and CHs-primary PTCA groups) or 800,000 units of intravenous monteplase, half the standard dose of a mutant tissue plasminogen activator (t-PA), followed by rescue PTCA if the Thrombolysis in Myocardial Infarction (TIMI) flow grade was 2 or less (TEC-monteplase and CHs-monteplase groups) on the first coronary angiogram. Sixty minutes after admission, TIMI flow grade 3 rates of the study groups were as follows, in descending order: TEC-monteplase group, CHs-monteplase group, TEC-primary PTCA group, and CHs-primary PTCA group (56%, 41%, 36%, and 8%, respectively; p<0.01). However, there was no significant difference in the final TIMI flow grade 3 rate among the 4 groups. In the CHs, the peak creatine kinase tended to be lower in the monteplase group than in the primary PTCA group. The results suggest that low-dose monteplase followed by rescue PTCA is an effective strategy for promoting early reperfusion in patients with AMI, especially those who are treated at CHs.
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PMID:Low-dose tissue plasminogen activator followed by planned rescue angioplasty reduces time to reperfusion for acute myocardial infarction treated at community hospitals. 1166 96

The efficacy and safety of fibrinolysis and subsequent transluminal (FAST) therapy were evaluated in 195 patients with acute myocardial infarction (AMI) for the early achievement of thrombolysis-in-myocardial-infarction grade 3 (TIMI-3) flow in the infarct-related artery. Intravenous thrombolysis using the optimal dose of a thrombolytic agent was initiated immediately after arrival in the emergency room, followed by coronary angiography and adjuvant percutaneous coronary intervention. A comparison of the thrombolysis alone (n=83) and thrombolysis plus intervention (n=112) groups showed significant differences in the time interval from hospital arrival to achievement of TIMI-3 flow (66.2+/-23.7 vs 111.6+/-29.6 min, p<0.0001), creatine kinase-MB release (295+/-201 vs 468+/-322 U/L, p=0.0003) and peak troponin T (23.6+/-16.9 vs 38.9+/-25.9 ng/ml, p<0.0001). No significant differences were observed in either 30-day mortality or complications. The TIMI-3 flow at the initial angiography was significantly higher with a single bolus of mutant tissue-type plasminogen activator (t-PA) monteplase than with an accelerated infusion of t-PA (60% vs 32%, p=0.005). In conclusion, the early restoration of TIMI-3 flow by FAST therapy reduced the degree of myocardial damage with a low risk of complications. TIMI-3 flow was achieved at an earlier stage with monteplase and this agent may be beneficial in the FAST therapy.
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PMID:An early and complete reperfusion strategy for acute myocardial infarction using fibrinolysis and subsequent transluminal therapy--The FAST trial. 1207 77

Phospholipases A(2) (PLA(2)s), of molecular mass 13-15kDa, are commonly isolated from snake venom. Two myotoxins with PLA(2) activity, BaPLA(2)I and BaPLA(2)III, with estimated molecular masses of 15kDa were isolated from the venom of Bothrops atrox using Sephacryl S-100-HR and reverse-phase chromatography. BaPLA(2)I was basic, with a pI of 9.1, while BaPLA(2)III was neutral with a pI of 6.9. On a molecular basis, BaPLA(2)III exhibited higher catalytic activity on synthetic substrates than BaPLA(2)I. Comparison of the N-terminal residues of BaPLA(2)I with other PLA(2) proteins from snake venoms showed that it has the highest homology (94%) with B. asper myotoxin II and homology with a PLA(2) Lys(49) from B. atrox (89%). In contrast, BaPLA(2)III demonstrated 75, 72, and 71% homology with PLA(2) from Vipera ammodytes meridionalis, B. jararacussu, and B. jararaca, respectively. BaPLA(2)I and BaPLA(2)III were capable, in vitro, of inducing mast cell degranulation and, in vivo, of causing creatine kinase release, edema, and myonecrosis typical of PLA(2)s from snake venoms, characterized by rapid disruption of the plasma membrane as indicated by clumping of myofilaments and necrosis of affected skeletal muscle cells. BaPLA(2)I- and BaPLA(2)III-specific monoclonal and polyclonal antibodies, although incapable of neutralizing PLA(2) edematogenic activity, blocked myonecrosis efficiently in an in vivo neutralization assay. The results presented herein suggest that the biological active site responsible for edema induction by these two PLA(2) enzymes is distinct from the myonecrosis active site and is not dependent upon the catalytic activity of the PLA(2) enzyme.
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PMID:Biochemical and biological properties of phospholipases A(2) from Bothrops atrox snake venom. 1223 22

Mechanical valve thrombosis is a life-threatening event. Pregnancy is associated with a hypercoagulable state that further emphasizes the importance of adequate anticoagulation. This is associated with a therapeutic dilemma. Continued anticoagulation with warfarin throughout the first trimester can result in fetopathic effects, while replacement of warfarin by heparin between 6 and 12 weeks of gestation does not completely prevent the risk of valve thrombosis. There are a small number of reported cases of pregnant women with prosthetic heart valve thrombosis under low molecular weight heparin and consecutive lytic therapy. The authors report a 33-year-old pregnant woman with a St. Jude Medical aortic prosthesis, anticoagulated with a therapeutic dosage of low molecular weight heparin from 6 weeks of gestation, who developed prosthetic heart valve thrombosis at 17 weeks of gestation. A thrombolysis with recombinant tissue-type plasminogen activator (50 mg for 2 hours) was performed. Under thrombolysis, ST-segment elevation in leads II, III, aVF, V5, and V6 developed electrocardiographically with a maximal creatine kinase (CK) of 349 U/L (CK-MB isoenzyme of 48 U/L). Echocardiography revealed normal function of the St. Jude Medical aortic prosthesis 2 hours after thrombolysis and normal wall motions. Short-course thrombolytic therapy appears to be an effective alternative to surgical intervention for the treatment of thrombotic dysfunction of valve prostheses in pregnancy.
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PMID:Successful thrombolysis of st. Jude medical aortic prosthesis with tissue-type plasminogen activator in a pregnant woman: a case report. 1239 Jun 90

In a previous report we showed that Lachesis muta crude venom displays potent indirect hemolytic activity and myotoxicity when injected into mice. Then, a phospholipase A(2) (PLA(2)) (LM-PLA(2)-I) responsible for these activities was isolated. More recently, a catalytically active isoenzyme (LM-PLA(2)-II) with molecular mass of 18 kDa and isoeletric point at pH 5.4 was isolated from the same snake venom. LM-PLA(2)-II inhibited ADP- and collagen-induced platelet aggregation as well as induced a potent paw edema reaction in rats. Here we show that LM-PLA(2)-II induced myotoxic effects both in vitro characterized by an increase on the rate of creatine kinase (CK) release from isolated mice extensor digitorum longus (EDL) muscles and in vivo by increasing plasma CK activity of injected mice. Histological analysis showed an intense damage in muscle cells injected with LM-PLA(2)-II. It was also shown that exogenous lysophosphatidylcholine (lyso-pc) behaved as a typical myotoxin damaging muscle cells, producing myonecrosis characterized by local infiltration of inflammatory cells similarly to that observed for LM-PLA(2)-II. Hemorrhage and lethal effects were not observed neither with LM-PLA(2)-II nor lyso-pc. As previously observed for other biological activities, pretreatment of LM-PLA(2)-II with p-bromophenacyl bromide (p-BPB) or acetic anhydride abolished all the enzyme's actions. The data confirms that biological activities displayed by LM-PLA(2)-II, including the myotoxic effects reported here, are all dependent on its enzymatic activity where the product formed (lyso-pc) may play an important function on such myotoxicity.
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PMID:Myotoxicity induced by an acidic Asp-49 phospholipase A(2) isolated from Lachesis muta snake venom. Comparison with lysophosphatidylcholine. 1281 42

To determine whether tenecteplase (TNK-t-PA), a bioengineered variant of tissue-type plasminogen activator (t-PA) designed to accelerate thrombolysis, exhibits favorable properties compared with those of alteplase, 266 men were studied </=6 hours after the onset of symptoms and signs of acute myocardial infarction. The primary end point was the rapidity of recanalization as judged from analysis of serial changes in the concentrations in blood of isoforms of creatine kinase-MM in serially obtained blood samples. Additional end points included enzymatically estimated infarct size and mortality. Patients were treated quite promptly after the onset of symptoms. The interval from the onset of chest pain to recanalization seen with TNK-t-PA was 208 +/- 10 (SE) minutes compared with 237 +/- 9 minutes seen with alteplase (p = 0.04). Thirty-day mortality was low with the use of the 2 agents (2%). TNK-t-PA appears to induce recanalization more rapidly than alteplase, and thrombolysis initiated early after the onset of symptoms is associated with remarkably low mortality.
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PMID:Comparison of rapidity of coronary recanalization in men with tenecteplase versus alteplase in acute myocardial infarction. 1519 14


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