Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An study was made in order to determinate the relationship between the restoration of the local fibrinolytic activity and the clinical signs in patients with a Raynaud's phenomenon. It is known that local fibrinolytic activity is a system influenced by changes into its components produced by exogenous and endogenous factors. An important role is represented by the t-PA and PAI-1. On the contrary, u-PA doesn't change. Samples were all taken at the same time, approximately at the middle of the morning. In patients with Raynaud's phenomenon treated with a prostacyclin stable analogous, we have perceived a clinical improvement, corresponding with a fibrinolytic activity increase.
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PMID:[t-PA and PAI in patients with Raynaud's syndrome in treatment with a stable prostacyclin analog]. 137 47

In order to investigate the significance of high circulating levels of von Willebrand factor (vWF), recently observed in patients with vascular diseases, we compared the plasma levels of vWF with those of tissue-type plasminogen activator (t-PA) and the platelet content of serotonin (5-HT) in 40 patients with Raynaud's phenomenon (RP), primary or associated to systemic sclerosis (SSc), and in 14 patients with chronic peripheral obstructive disease due to arteriosclerosis (PAOD). VWF and t-PA plasma levels were significantly increased (p < 0.001) in SSc (vWF: 158.2, range 116.3-305.0%; t-PA: 10.2, range 6.4-17.8 ng/ml). By contrast, normal plasma levels of both vWF (85.3, range 53.5-157.0%) and t-PA (6.5, range 2.7-9.3 ng/ml) were observed in primary RP. VWF and t-PA were normal in PAOD patients, compared with age-matched healthy controls (vWF: 143.0, range 57.0-204.0%; t-PA: 7.5, range 3.4-13.6, ng/ml). The platelet content of 5-HT was within the normal range (37.3-99.7 ng/10(8) platelets) in RP patients, but significantly reduced (P < 0.05) in PAOD patients (39.0, range 14.7-91.4). Our data suggest that the different pattern of circulating vWF and t-PA between SSc and arteriosclerotic patients may be related to a different endothelial cell involvement. Whether this increase may reflect active attempts of regeneration and repair, indicating endothelial cell viability rather than damage is a matter of speculation.
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PMID:Tissue-type plasminogen activator and von Willebrand factor plasma levels as markers of endothelial involvement in patients with Raynaud's phenomenon. 145 97

Since L-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects of L-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynaud's phenomenon. After therapy, patients with Raynaud's phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.
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PMID:L-arginine therapy in Raynaud's phenomenon? 181 64

Twenty outpatients presenting with Raynaud's phenomenon secondary to clinical or preclinical inflammation of connective tissue were treated orally with defibrotide 400 mg three times daily or a matching placebo in a randomized double-blind study. The test product defibrotide (a polydeoxyribonucleic acid compound of animal origin with demonstrated profibrinolytic activity when administered parenterally) was administered orally for 3 weeks in order to explore its effects on the parameters of extrinsic fibrinolysis before and after venous stasis. The antigen of t-PA and its inhibitor PAI, free and total, and the biologic activity of PAI were assayed in basal conditions and after treatment. Although a marked increase of t-PA was seen with the active treatment, PAI activity was significantly reduced by defibrotide. Immunoreactive PAI was not significantly modified by treatment, even though it dropped considerably after venous stasis in the defibrotide group. Thus, the disturbance of endothelial function that seems to occur in vasculitis and in Raynaud's phenomenon secondary to inflammation of connective tissue (or so suspected to be) would constitute the basis of a disturbance of fibrinolysis, which oral defibrotide seems able to correct. Further studies are warranted to define the clinical effectiveness of this treatment in patients with Raynaud's phenomenon.
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PMID:Deficient fibrinolytic response in patients with Raynaud's phenomenon and its correction with defibrotide. 206 63

We describe a patient with systemic sclerosis (SSc; scleroderma) characterized by severe Raynaud's phenomenon, cutaneous sclerosis, and digital ulceration and subsequent amputation who was treated with recombinant tissue plasminogen activator (rt-PA) after acute myocardial infarction. She showed prompt improvement of the Raynaud's phenomenon and healing of the digital ulceration. After 18 months of followup, the Raynaud's phenomenon has remained mild, and there has been improvement in the cutaneous sclerosis. Since the pathophysiology of SSc has been associated with disorders of fibrinolysis and coagulation, this patient represents an interesting index case that might prompt further evaluation of rt-PA therapy in carefully selected patients.
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PMID:Prolonged improvement of Raynaud's phenomenon and scleroderma after recombinant tissue plasminogen activator therapy. 210 27

Defibrotide is a deoxyribonucleic acid derivative extracted from mammalian organs, which has been developed for the treatment of a number of vascular disorders. It appears to increase fibrinolysis and may possess antithrombotic, antiatherosclerotic and anti-ischaemic actions, probably due to its ability to selectively increase prostaglandin I2 and E2 levels and to increase tissue plasminogen activator and decrease plasminogen activator inhibitor function. Defibrotide is available as an intravenous and intramuscular preparation, and also as an oral formulation for long term use. Trials performed to date have provided initial evidence that defibrotide is effective in the treatment of peripheral obliterative arterial disease and acute thrombophlebitis, while preliminary data suggest possible use in preventing fibrin deposition in the circuitry of renal haemodialysis equipment. Efficacy in preventing deep vein thrombosis after surgery has been demonstrated but defibrotide does not appear to offer any therapeutic advantage over heparin. Further clinical experience is required in other disorders, including acute myocardial infarction, Raynaud's phenomenon, renal thrombotic microangiopathy and renal transplant rejection, before adequate assessment of efficacy in these areas can be made. Defibrotide is well tolerated, as assessed in trials of up to 6 months duration, with a low global incidence of adverse events (< 1 to 9%). Mild allergic reactions and gastrointestinal disturbances have occasionally been described, and a hypotensive effect has also infrequently been observed. Thus, available data suggest that defibrotide is a well tolerated agent with little or no anticoagulant activity, which is conveniently available in both parenteral and oral formulations. Initial data indicate that the drug may be a useful alternative in the treatment of peripheral obliterative arterial disease and thrombophlebitis, while its therapeutic potential in other vascular disorders and efficacy relative to established agents remains to be fully determined.
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PMID:Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. 768 75

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma levels of tumor necrosis factor and endothelial response in patients with chronic arterial obstructive disease or Raynaud's phenomenon. 798 28

In 15 patients with systemic sclerosis (SS) and 8 patients suffering from silicosis and/or silica dust exposure-associated scleroderma (SAS), various parameters of endothelial cell and platelet function and of blood coagulation and fibrinolysis were studied. In 9 of the 23 patients the values for the von Willebrand factor antigen were increased, and the same applied to the endothelin levels in 8 of 23 patients. Protein C, protein S, anti-thrombin III and tissue plasminogen activator (before and after 10 min venous occlusion) were normal. The plasminogen activator inhibitor, however, was increased in 5 patients. Increased levels of platelet factor 4 and of beta-thromboglobulin were found in 20 patients, while the ADP- and epinephrine-induced platelet aggregation was reduced in 5 patients. No individual patient was found to have a general disturbance of all parameters. The deviations in the parameters of endothelial cell and platelet function and of blood coagulation and fibrinolysis proved to be rather inconsistent. This suggests different functional stages in dependence on the various influential factors. There was no close correlation either with the severity of Raynaud's phenomenon or with the type of SS. In addition, there were no basic differences between SS and SAS. The disturbances occurred with similar frequency and in similar proportions in both disease groups.
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PMID:[Vascular function parameters in idiopathic and quartz-induced progressive scleroderma]. 827 90

A thirty-one-year-old woman with long-standing mixed connective tissue disease and severe obliterative vasculopathy of the digits developed digital thrombosis of the first three digits of the left hand after using an electric blow dryer. The digits remained cool, cyanotic, and painful for thirty-six hours before medical evaluation. She was given 100 mg recombinant tissue plasminogen activator (TPA) intravenously. Within one hour the blood flow to the digits returned, accompanied by severe intermittent vasospasm of the digits. The thumb did not necrose; however, the second and third digits required amputation. No improvement was noted in the patient's baseline Raynaud's phenomenon or digital pressures of the uninvolved digits after TPA treatment. This case documents the usefulness of TPA for digital thrombosis in the setting of vasculopathy of connective tissue disease. However, it does not support the utility of a single dose of TPA for severe Raynaud's phenomenon and recurrent digital ischemia in patients with connective tissue disease.
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PMID:Tissue plasminogen activator treatment of digital thrombosis in severe Raynaud's phenomenon--a case report. 832 85

We investigated the effect of beraprost sodium (BPS) on the Raynaud's phenomenon on 15 patients with systemic sclerosis, 3 with mixed connective tissue disease and 1 with Raynaud's disease, respectively. After 12 weeks of administration of 60 micrograms/d BPS, the duration and the incidence of the Raynaud's symptom were significantly reduced and the dermal temperature on the fingers was found to be elevated. Of the parameters which are known to reflect vascular endothelial damages such as tissue plasminogen activator (t-PA), von Willebrand's factor (vWF) and endothelin, the plasma level of t-PA was significantly reduced by BPS. Furthermore, the capillary loop in the nail bed of the fingers seemed to increase in one patient by the treatment with BPS. These results suggest that BPS has a capacity to repair peripheral vascular damages resulting in the improvement of Raynaud's phenomenon.
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PMID:[The effect of beraprost sodium on the Raynaud's phenomenon]. 881 May 44


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