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 this study the authors attempted to restore the coagulative fibrinolytic homeostasis that is compromised in peripheral vascular disease. Eleven patients with arterial disease, eleven with venous disease and seven healthy volunteers underwent oral treatment using 3 g of propionyl-L-carnitine divided into thrice daily doses for a period of 20 days. (1 g t.i.d.). This quaternaria amine is able to correct tissue hypoxia by increasing ATP and energy production and has the capacity to prevent alterations in endothelial membrane permeability. The authors observed a significant increase of t-PA synthesis on the 10th day of therapy in the arterial disease and control groups. All three groups showed a significant increase in t-PA synthesis on the 20th day of therapy. A significant decrease in PAI-1 activity was observed on the 10th and on the 20th day of therapy in both the patient groups, but not in the control group. Although the exact pathological mechanisms of peripheral vascular disease are complex and in many aspects still unknown, it is now absolutely certain that there is a pathogenetic role of functional imbalances. An important part is played by the reduction in t-PA synthesis and the increase in PAI-1 activity, and the authors conclude that it is necessary to use pharmaceutical substances to restore proper equilibrium.
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PMID:The action of propionyl-L-carnitine on the vasal endothelium: increased t-PA synthesis and a decrease in the activity of PAI-1. A preliminary study. 129 17

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.
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PMID:Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study. 1113 57

Thromboembolic venous disease includes deep vein thrombosis of the lower limbs and pulmonary embolism, a common acute complication. The usual treatment is anticoagulation. Thrombolytic drugs are only used in severe cases. Of the thrombolytic agents and therapeutic protocols in use, alteplase 100 mg/2 hours seems to be the best compromise between the risk of bleeding and efficacy in reducing pulmonary resistances by 30 to 40% and relatively early pulmonary revascularisation of 40-50%. As in myocardial infarction, cerebral haemorrhage is the main complication and the risk is higher in elderly (over 70 years of age) patients who have undergone invasive procedures. Massive pulmonary embolism, defined by clinical criteria, is presently the only formal indication of thrombolysis in this context. In non-massive embolism with right ventricular dysfunction, thrombolysis could also be indicated in the absence of haemorrhagic risk. In deep vein thrombosis of the lower limbs, the role of thrombolysis is limited and controversial; in many cases, the risk of haemorrhage is greater than the potential benefits.
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PMID:[Fibrinolytics in venous thromboembolic disease]. 1179 77

Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cell-derived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Society of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.
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PMID:Alteplase and tenecteplase: applications in the peripheral circulation. 1198 95

To determine if patients who suffer atherothrombotic ischemic stroke have altered release of tissue plasminogen activator (t-PA), we measured levels in 22 patients within 24 h of onset of symptoms and 1-2 months later. t-PA levels were measured in blood samples by using a colorimetric method after subjecting the plasma to euglobulin fractionation and reacting it with plasminogen and plasmin substrate. Values from a group of normal volunteers previously studied were used as controls. Individual variability in t-PA levels was found acutely and in the recovery phase. During the latter, patients' levels were significantly higher than controls, which was not the case in the acute phase. There was no correlation among t-PA levels, size of cerebral infarct, and patients' clinical status. We propose that endothelial repair and a rebound in endogenous fibrinolytic activity in the absence of peripheral venous disease are responsible for the late (recovery phase) elevation in t-PA.
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PMID:Releasable tissue plasminogen activators in ischemic stroke. 2648 66