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)

In the early stages of anaphylactic shock of rats pretreated with Bordetella pertussis vaccine, a prompt and parallel activation of the factor XIIa-dependent intrinsic coagulation, kinin generation, and fibrinolytic acticity was observed. The coagulation studies, the similarity of anaphylactic results with those produced by a single injection of ellagic acid, and the effective inhibition of the anaphylactic and the ellagic acid-induced activation of these pathways by lysozyme all suggest that factor XII itself becomes activated in rat anaphylaxis. As the reaction proceeded, considerable anticoagulant activities emerged, but the bradykinin and the plasminogen activator levels even further increased. During the first 10 min of anaphylactic shock, factor XII was partly consumed and this was prevented by epsilon-aminocaproic acid infusion. The results show that in pathological conditions such as anaphylaxis there is an intimate in vivo interaction among the three factor XIIa-dependent pathways.
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PMID:Activation and consumption of Hageman factor in the anaphylactic shock of the rat. 96 6

Anaphylactic shock was induced in rabbits by injecting bovine serum albumin (BSA) as an antigen. Measurements of the enzyme activities in the fibrinolytic system confirmed that a rapid and strong increase of plasminogen activator (PA) was induced during anaphylaxis. The euglobulin fibrinolytic activity (EFA) as estimated by the plasminogen-rich fibrin plate method rose significantly, peaking at 15 min after the BSA injection (when the arterial pressure was minimum). However, EFA was not detected by the plasminogen-poor fibrin plate method. The tissue-type PA (t-PA) activity using the natural substrate plasminogen increased significantly with a peak at 15 min. The amidolytic activity also simultaneously increased significantly using the t-PA substrate, H-D-Ile-Pro-Arg-pNA. The plasminogen activator inhibitor (PAI) activity remained at baseline levels until 30 min, but rose fourfold at 90 min. The main plasma fibrinolytic enzyme which increased in anaphylaxis was proved by zymography to be t-PA with a molecular weight (MW) of 69,000.
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PMID:A rapid and strong increase of plasminogen activator induced by experimental anaphylaxis in rabbits. 129 30

Understanding the clinical risks of intravenous thrombolytic therapy is critical to appropriate patient selection. The major risks can be classified into 5 major categories: intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Although theoretical concern exists about thromboembolic complications, they rarely occur. Although cardiac rhythm disturbances are somewhat more likely to occur at the time of reperfusion, the clinical significance of "reperfusion arrhythmias" is minimal. Intracranial hemorrhage, the most devastating complication, occurs in 0.2-1% of patients treated with thrombolytic therapy. Factors associated with incremental risk are now being identified from large clinical trials. Systemic hemorrhage is uncommon in patients without major vascular punctures and seldom leads to serious adverse outcomes. Immunologic complications--including anaphylaxis, which is rare, and immune complex disease, which is more common--occur only with streptokinase or agents with a streptokinase moiety, including anistreplase (anisoylated plasminogen--streptokinase activator complex, APSAC). Hypotension, which can be managed easily in most patients, is also observed much more frequently with streptokinase and anistreplase. Myocardial rupture is increasingly being recognized as a possible complication of late thrombolysis. A proper perspective on clinical risk can only be gained in the context of potential benefit of therapy. In many cases individual patients considered to be at highest risk for complications also stand to gain the most from treatment. Many of the questions raised by currently available data about bleeding risk are being addressed in the ongoing Global Utilization of t-PA and Streptokinase (GUSTO) Trial. A paradigm for considering this decision making problem is presented.
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PMID:Clinical risks of thrombolytic therapy. 172 75

LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 mumol kg-1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 mumol kg-1. An attempt was made to elucidate the mechanism of LG 30435's action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action.
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PMID:Mechanisms of the antiallergic action of N-methylmequitazine (LG 30435). 290 Mar 3

The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.
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PMID:Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. 311 26

REV 3164 has been evaluated in a variety of intact rodent models to reveal potential utility in the prophylactic treatment of asthma. REV 3164 was found a potent, orally active inhibitor of rat (IgE) passive cutaneous anaphylaxis (PCA, ED50 = 0.9 mg/kg). By contrast, at 50-200 mg/kg p.o., it did not affect guinea-pig (IgG1) PCA. In PCA rats, both REV 3164, 1-36 mg/kg i.p., and the known inhibitor of mast cell mediator release, disodium cromoglycate (DSCG), 2-54 mg/kg i.p., blocked cutaneous wheals caused by i.v. antigen challenge but not by intradermal serotonin or histamine. Neither REV 3164 (0.1-10 mg/kg i.p.) nor DSCG (2-54 mg/kg i.p.) affected Compound 48/80-induced wheals. REV 3164 (0.01-1 mg/kg i.v. or 10 mg/kg i.p.) abolished rat (IgE) passive lung anaphylaxis (PLA, ED50 = 0.05 mg/kg i.v. for inhibition of elevated airway resistance). At 10 mg/kg i.p., REV 3164 did not affect active lung anaphylaxis in guinea-pigs pharmacologically manipulated to enhance the production and action of slow reacting substance of anaphylaxis (SRS-A), nor did it exhibit anticholinergic activity in the rat. REV 3164 (100 mg/kg i.p.) did not protect conscious guinea-pigs from histamine aerosol-induced collapse. It is concluded that REV 3164 is an oral inhibitor of IgE-dependent immediate hypersensitivity in the rat with biological activities in rats and guinea-pigs similar to DSCG.
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PMID:In vivo anti-allergic and bronchopulmonary pharmacology of REV 3164 in rats and guinea-pigs. 649 6

Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag-coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy.
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PMID:Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice. 1120 23

Streptokinase was discovered in 1933. Its importance has gradually grown since 1950's of the last century when it was used as the utterly first thrombolytic agent. Since the discovery that majority of acute myocardial infarctions is caused by thrombus in the area of ruptured endothel above the atherosclerotic platelet, it has become the first remedy able of real causal treatment of acute myocardial infarction (AMI). These days it becomes an obsolete remedy because of a range of disadvantages. Neutralizing antibodies for instance remain in organism for many years after its administration, which results in an inefficacious treatment. Moreover it causes allergic reactions or anaphylaxis in a part of population, hypotension, and decrease of its fibrinolytic effect after more then 3 hours after development of AMI. The most problematic is its anticoagulant effect lasting more than 24 hours after its administration and simultaneous increase in prothrombotic activity, which is a disadvantage if intervention treatment methods are appropriate (direct coronary angioplasty). The only advantage of streptokinase is its relatively low price. However, it cannot justify its use as a thrombolytic agent of the first choice and it is high time for it to be replaced in its treatment indications by plasminogen activator or by thrombolytic agents of the third generation derived from it, which can be conveniently administered in the bolus form.
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PMID:[Does streptokinase still have a role in the treatment of acute myocardial infarct?]. 1468 79

Anaphylactoid reaction to recombinant tissue plasminogen activator for the thrombolytic treatment of acute ischemic stroke is an uncommon complication. An increased risk of anaphylaxis may be found in patients concomitantly being treated with angiotensin-converting enzyme inhibitors, as illustrated by this case report describing a patient who experienced an urticaric rash, hypotension, tachycardia, orolingual angioedema, and airway obstruction following intravenous administration of alteplase. Possible pharmacologic interactions resulting in excessive serum bradykinin and subsequent systemic hypersensitivity responses are discussed.
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PMID:Anaphylactoid reaction to recombinant tissue plasminogen activator. 1719 33

Central venous catheter (CVC) occlusion occurs frequently and remains a significant clinical problem in patients with cancer receiving infusional or intravenous chemotherapy. Thrombotic occlusions frequently limit the benefits of potentially curable cytotoxic agents by interrupting the delivery of infusion of chemotherapy, intravenous medication, nutritional support, and blood products, as well as the frequent acquisition of venous blood samples for laboratory testing. Urokinase has been used as a thrombolytic agent for dysfunctional occluded CVCs, but the alterations in manufacturing practice prompted the Food and Drug Administration to suspend further production of urokinase in 1999. Although streptokinase had a potential as a thrombolytic agent in place of urokinase, the risk of life-threatening anaphylaxis associated with this agent prompted researchers to look for newer agents to dissolve CVC occlusions. Several novel thrombolytic agents are currently being evaluated as a potential treatment for patients with CVC occlusions and acute or chronic peripheral arterial occlusions. Alfimeprase, a recombinant fibrinolytic zinc metalloprotease, has shown promising clinical utility in blood clot lysis in patients with CVC occlusions and peripheral arterial occlusions. Based on the encouraging data, alfimeprase has received orphan drug designation from the Food and Drug Administration and the Committee for Orphan Medicinal Products of the European Medicines Agency for the evaluation of acute peripheral arterial occlusions as a potential indication. Other novel thrombolytic agents such as alteplase and reteplase are undergoing clinical evaluation for their utility in restoring the function of occluded CVCs. The clinical potency of these novel agents and their ongoing clinical trials are discussed briefly herein.
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PMID:Clinical utility of novel agents in the treatment of central venous catheter occlusion. 1863 86


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