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

Patients with acute coronary syndromes (ACS) frequently present with signs of disturbed fibrinolysis. The present study investigates the correlation of alterations in the fibrinolytic system and the amount of myocardial damage characterized by troponin release. In 85 patients with ACS markers of plasmin activation, plasminogen activator system and troponin T (TnT) were measured initially and after 48 h. Patients with TnT release (> or = 0.01 microg/l) at admission had higher TPA levels than those without release (10.2+/-0.7 ng/ml vs. 7.6+/-0.5 ng/ml; p <0.01). Additionally, patients with positive TnT had higher D-dimer levels initially (457+/-39 ng/ml vs. 316+/-22 ng/ml; p <0.01) and 48 h later (451+/-42 ng/ml vs. 275+/-37 ng/ml; p <0.01). The association of myocardial damage with a prothrombotic state and an enhanced fibrinolysis may explain the high prognostic value of troponin measurements in respect to future coronary events.
 ...
PMID:Myocardial troponin T release is associated with enhanced fibrinolysis in patients with acute coronary syndromes. 1181 3

In Italy (130,000 new strokes in the general population per year) ischemic stroke is the third cause of death, after cardiovascular disease and neoplastic disease with a prevalence of 6.5%. Different physicians are involved in the emergent evaluation and treatment of the acute ischemic stroke. As other acute events, the initial evaluation must be addressed to assess the patient's airway and breath-ing and cardiocirculatory conditions. The neurological examination must not be exhaustive and it should be completed in 5-10 minutes and a particular attention should be given to clinical findings leading to the suspect of an intracranial hemorrhages. A plain CT scan of the brain is the most important initial diagnostic study. Emergency therapy must be mainly directed to the correction of hypovolemia, hypoxia and the treatment of severe hypertension, hypoglycemia, intracranial hypertension and seizures. The goal is to achieve and to maintain an adequate cerebral perfusion by lowering the intracranial pressure (treating the cerebral oedema) and by increasing the mean arterial pressure, with an appropriate volemic expansion and/or with inotropic or vasopressor drugs. The thrombolytic therapy with intravenous recombinant tessutal plasminogen activator (r-TPA) when not specifically contraindicated, is recommended within 3 hours of onset of ischemic stroke. The benefit of intravenous r-TPA for acute ischemic stroke beyond 3 hours from the onset has never been proved.
 ...
PMID:Stroke patients, what to do and what to avoid. 1202 99

ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.
 ...
PMID:Outcome of acute myocardial infarction in patients with prior coronary artery bypass grafting treated with combination reduced fibrinolytic therapy and abciximab. 1245 May 98

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced the chronic model of inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the leukocyte infiltration, measured as tissue peroxidase activity. In the case of the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3 inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against cells at 100 microM.
 ...
PMID:Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits. 1464 90

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.
 ...
PMID:Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. 1498 20

Tissue plasminogen activator (tPA) is the predominant plasminogen activator present in the vascular and nervous systems. Prior studies of the two have emphasized different tPA sources; respectively, endothelium and neurons. A closer relationship is now suggested by evidence that the peripheral sympathetic nervous system synthesizes and infuses enzymatically active tPA into small artery walls and the microcirculation. TPA may thus be the only known neural product able to effect degradation of the artery wall extracellular matrix. This brief review considers historical and current indications for the existence of such an autonomically controlled system and some physiologic implications. Immunohistochemical tPA expression in small arteries and arterioles is more prominent in the outer wall sympathetic axon plexus than in endothelium. Its presence in nerve filaments beneath the seldom-studied adventitia was obscured in earlier localizations. The systemic impact of a neural distribution is suggested by a 60% reduction of blood tPA activity after chemical sympathectomy. TPA-bearing axons extend outward from ganglion neuron cell bodies to reach even thin-walled vasa vasora and uveal microvessels. Ganglion cell bodies synthesize and package tPA in vesicles for the long axoplasmic transport. Densely innervated intact vessels release much greater amounts of tPA in vitro than do larger vessels, indicating a high neuron tPA production capacity and a large storage reservoir available within axon networks. The influence of an autonomically controlled plasmin production within small artery walls on regulation of blood pressure and capillary perfusion awaits further investigation. Its possible role in the pathogenesis of vessel wall matrix degradations in aging, hypertension, and diabetes may also merit further consideration.
 ...
PMID:Distribution of sympathetic tissue plasminogen activator (tPA) to a distant microvasculature. 1567 11

Since July 2002 we have been conducting a study of efficacy of prehospital thrombolytic therapy combined with subsequent endovascular procedures in the treatment of patients with acute myocardial infarction. Fifty nine patients received prehospital fibrinolysis with tissue-type plasminogen activator (TPA, n=28) or streptokinase (n=31) within 6 hours after onset of symptoms. TPA infusion compared with that of streptokinase was associated with smaller ischemic myocardial damage and lower frequency of side effects (3.6 and 38.7%, respectively). Angioplasty or stenting of infarct related arteries were carried out in 47 of these patients. The group of patients subjected to endovascular interventions was characterized by a low rate of in-hospital cardiac events and zero mortality.
 ...
PMID:[Combination of prehospital systemic thrombolytic therapy with endovascular procedures in the treatment of patients with acute myocardial infarction]. 1582

Ultrasound (US) has emerged as a new tool to treat ischemic stroke. The potential advantage of US is decreased risk of systemic bleeding complications due to its site-specific effect. Moreover, external application is noninvasive and is readily available. Experimental studies showed that low intensity (<or=2W/cm2) US safely enhanced thrombolytic drug activity within a wide range of frequencies (0.04-3.4 MHz). In humans, transcranial sonothrombolysis with mid-kHz frequencies showed an unacceptably high rate of intracranial bleeding, while the use of 2MHz yielded promising results in The Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic TPA (CLOTBUST) study. This study was a phase II randomized clinical trial that included patients with middle cerebral artery (MCA) occlusion within 3 h of stroke onset, who were treated with standard dose of tissue plasminogen activator (t-PA). Residual flow in MCA was monitored with 2MHz US in one group, and the rate of complete recanalization and dramatic clinical recovery significantly increased as compared to t-PA alone. This chapter further discusses diagnosis of an acute occlusion and recanalization using the thrombolysis in brain ischemia (TIBI) waveform flow grading scale, application of fast track insonation protocol, and administration of US. Also, the potential enhancement of sonothrombolysis with microbubbles is discussed.
 ...
PMID:Acute stroke: therapeutic transcranial Doppler sonography. 1729 Jan 34

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. It manifests as acute focal inflammatory demyelination and axonal loss with limited remyelination and results in the chronic multifocal sclerotic plaques. Previously published data showed impaired fibrinolysis in MS. Tissue plasminogen activator t-PA is a serine protease that catalyses the activation of plasmin, which mediates the effects of fibrinolytic system. Alu insertion/deletion (I/D) genetic polymorphism in TPA gene in MS patients has not been analysed previously. The major inhibitor of t-PA is plasminogen activator inhibitor-1 (PAI-1). Its gene expression is modulated by functional genetic polymorphism in the promoter (4G/5G). In the present study, an association of two genetic polymorphisms with MS, its progression and subtype were analysed. TPA DD/PAI-1 4G4G genotype combination has reached a borderline significance for reduced risk for MS (OR = 0.543, 95% CI 0.301-0.978, P = 0.04), suggesting a gene-gene interaction. The explanation for this interaction may be a complex interplay between these two pleiotropic proteins within the brain tissue and in plasma.
 ...
PMID:PAI and TPA gene polymorphisms in multiple sclerosis. 1798 6

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Caucasian subjects. The aim of this study was to identify the contributions of genetic and other factors to inter-individual variation in plasma levels of t-PA and PAI-1 in a large-scale population-based sample from urban West Africa. t-PA, PAI-1 and several demographic, anthropometric, and metabolic parameters were measured in 992 residents of Sunyani, the capital of the Brong-Ahafo region of Ghana. In addition, nine gene polymorphisms associated with components of the renin-angiotensin and fibrinolytic systems were determined. We found that BMI, systolic and diastolic blood pressure, total cholesterol, glucose, and triglycerides were all significant predictors of t-PA and PAI-1 in both females and males. In addition, a significant relationship was found between the PAI-1 4G/5G (rs1799768) polymorphism on PAI-1 levels in females, the TPA I/D (rs4646972) polymorphism on t-PA and PAI-1 in males, the renin (rs3730103) polymorphism on t-PA and PAI-1 in males, the ethanolamine kinase 2 (rs1917542) polymorphism on PAI-1 in males, and the renin (rs1464816) polymorphism on t-PA in females and on PAI-1 in males. This study of urban West Africans shows that t-PA and PAI-1 levels are determined by both genetic loci of the fibrinolytic and renin-angiotensin systems and other factors often associated with cardiovascular disease, and that genetic factors differ between males and females.
 ...
PMID:Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. 1895 68


<< Previous 1 2 3 4 Next >>