Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Limb ischemia, both acute and chronic, presents a risk to life and limb with mortality rates from 3% to 37% and amputation rates of the same range. Our experience with urokinase thrombolysis as the initial therapy for acute and non-acute ischemic extremities over 57 consecutive cases of native arterial occlusion by either thrombus or embolus has resulted in no mortality and only 3.5% requiring amputation (2 of 57). In 74% of cases initial thrombolytic therapy was followed by either balloon angioplasty (35 patients) or surgery (7 patients) to relieve the underlying cause of obstruction (i.e., stenosis, occlusion or aneurysm). Thrombolysis alone was sufficient and effective treatment in the remaining 26% (15 patients).
...
PMID:Urokinase thrombolysis as initial therapy for acute and non-acute ischemic extremities. 900 54

Symptomatic end-stage arterial disease in coronary artery or peripheral arterial occlusive disease represents an increasing clinical problem as cardiovascular mortality in these patient groups has declined due to improved secondary prevention. While in peripheral arterial occlusive disease amputation with subsequent life-long physical disability is the major problem, patients with end-stage coronary artery disease and refractory angina pectoris repeatedly report to the emergency ward with the clinical symptoms of unstable coronary syndromes, but myocardial infarction is generally ruled out. For these patients long-term intermittent urokinase therapy has been developed as an alternative treatment modality. Potential mechanisms for clinical effectiveness include improvement of rheological blood properties, thrombolysis of non-occluding arterial thrombi and possibly plaque regression. In coronary artery disease urokinase is applied as an intravenous bolus injection of 500,000 IU urokinase three times a week over a period of 12 weeks. This leads to a marked reduction of fibrinogen by about 35% and of clinical symptoms by around 70% accompanied by a reduction of exercise-induced myocardial ischemia. In observational studies in patients with peripheral arterial occlusive disease injections of 500,000 IU of urokinase were usually given daily for a shorter time period of three to four weeks with a clinical success rate, defined as a cessation or marked reduction of rest pain and/or salvage of a limb, of around 50%. Given the state of critical ischemia in both entities of atherosclerotic disease, long-term intermittent urokinase therapy represents a promising antiischemic approach. In particular in patients with peripheral arterial occlusive disease randomized controlled trials with prolonged treatment periods, which are likely to improve clinical results, are warranted.
...
PMID:Low-dose intermittent urokinase therapy in chronic symptomatic end-stage arterial disease--clinical relevance for patients with coronary artery disease or peripheral arterial occlusive disease. 918 59

Although glycosylphosphatidyl-inositol (GPI) linked membrane proteins do not possess transmembrane or cytosolic sequences they elicit transmembrane signals. Using microscopic fluorescence imaging and resonance energy transfer (RET) techniques we have shown that certain pro-inflammatory GPI-linked membrane proteins can interact with leukocyte beta 2 integrins (complement receptor type 3 (CR3) and 4 (CR4) and the leukocyte function-associated antigen-1 (LFA-1)). For example, physical associations between CR3 and Fc gamma RIIIB, CR3 and urokinase receptors, and CR3 and CD14 (lipopolysaccharide receptor) have been found. Although Fc gamma RIIIB appears to be constitutively associated with CR3, urokinase receptors and CD14 associations with CR3 are influenced by their ligation status and cell function (e.g. adherence and locomotion). CR3-to-urokinase receptor interactions have been confirmed by immunoprecipitation techniques. Immunoprecipitation of CR3 from Brij-58 lysates after biotinylation of neutrophil membranes revealed proteins of M(r) = 40,000, 50,000, 74,000 and 120,000, in addition to bands corresponding to the integrin alpha and beta chains. Cell functions such as transmembrane signaling and superoxide release/priming have been linked to these interactions. Importantly, reagents that affect the lectin-like site of CR3, such as N-acetyl-D-glucosamine, alpha-methyl-D-mannoside and beta-glucan alter these interactions and, in parallel, leukocyte functions. Thus, the interactions of GPI-linked proteins and integrins can be highly dynamic events linked to cell activities. Our studies suggest that it may be possible to develop new drugs directed at the lectin-like site of beta 2 integrins that block GPI-linked protein-to-integrin coupling thereby controlling inflammatory cell processes including cell adherence, locomotion and activation. Such drugs may be useful in clinical conditions such as ischemia-reperfusion injury, sepsis, arthritis and others.
...
PMID:Ectodomain interactions of leukocyte integrins and pro-inflammatory GPI-linked membrane proteins. 922 70

Acute hand ischemia is a medical emergency requiring immediate treatment. We report a case of acute hand ischemia due to a crush injury of the wrist. Management with urokinase was successful in reestablishing flow to the ulnar artery and the digital vessels. In the setting of acute trauma with extensive thrombosis of the vessels of the hand, thrombolytic therapy may offer a better treatment option than surgical exploration with bypass grafting.
...
PMID:Successful hand revascularization with urokinase following a crush injury. 922 1

The outcomes of intra-arterial urokinase versus surgery for acute peripheral arterial occlusion (PAO) were compared. Patients at a university hospital who had received intraarterial urokinase for PAO were identified by computer and pair-matched on the basis of comorbidities, age, sex, and site of occlusion to computer-selected patients who had undergone surgery. Only patients with category I or II ischemia were considered. The study period for the urokinase group was February 1995 through January 1996, and the period for the surgery group was June 1993 through January 1996. Twenty-eight patients in each group met the selection criteria. Patients who had received urokinase had a significantly shorter median length of stay (8.5 days) than patients in the surgery group (13 days) and significantly fewer infectious complications (2 versus 10). No differences in amputation rates, total hospital costs, or mortality rates were detected. Patients who received intra-arterial urokinase for PAO had a shorter length of stay in the hospital and fewer infectious complications than those who underwent surgery.
...
PMID:Intra-arterial urokinase versus surgery for acute peripheral arterial occlusion. 929 Aug 93

In order to investigate the influences of taurine on thrombolysis serum endothelin (ET) concentration was determined in patients with acute myocardial infarcation (AMI) without urokinase (UK) treatment (group 1) and after treatment with UK (group 2) or UK combined with taurine (group 3). In a rat model with abdominal aorta thrombosed by FeCl3, the changes of serum ET, malodialdehyde (MDA) and intravascular thrombosis were observed in three groups same as in patients. The results were as follows: (1) Serum ET levels of group 1 patients at early phase of onset (6 hours) were significantly higher than those of the controls (47.3 +/- 6.3 ng/L vs 20.4 +/- 9.7 ng/L, P < 0.001). After two days serum ET decreased to normal level. Serum ET levels were significantly higher from 6 to 10 hours after the onset of AMI in group 2 than in group 1 (70.8 +/- 6.6 ng/L vs 56.9 +/- 8.6 ng/L, P < 0.01, at 8 hours). Serum ET levels were significantly lower from 8 hours to a week after onset of AMI in group 3 than in group 2 (33.3 +/- 8.2 ng/L vs 70.8 +/- 6.6 ng/L, P < 0.01, at 8 hours). (2) In the rat model with thrombosis of abdominal aorta, the changes of serum ET were similar to those of AMI patients. In addition serum MDA levels were significantly decreased (20.85 +/- 3.05 mumol/L vs 25.18 +/- 3.53 mumol/L after combined treatment with UK and taurine, P < 0.05). The ratio of cross area of vascular lumen and thrombus was lower after treatment with combination of UK and taurine than treatment with UK alone (0.4650 +/- 0.0928 vs 0.6176 +/- 0.1179, P < 0.05), the results suggested that taurine can decrease significantly serum ET levels, potentiate UK-induced vascular recanlization and reduce ischemia reperfusion injury. Taurine might be useful clinically as an adjunct of thrombolytic therapy.
...
PMID:[Influences of taurine on thrombolysis]. 938 24

Pneumonia is the most common serious complication of varicella infection in adults. A variety of thrombotic complications including purpura fulminans and disseminated intravascular coagulation have been reported in children with varicella but not in adults. Two men with varicella pneumonia who had profound lower extremity ischemia caused by thrombosis of the profunda femoris and tibial arteries are reported. Both patients had free protein S deficiency and vascular thrombosis in association with varicella pneumonia without overt evidence of disseminated intravascular coagulation or purpura fulminans. Antiphospholipid immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the other had evidence of the lupus anticoagulant. The proposed pathogenesis and management options including intraarterial thrombolytic therapy with urokinase and the need for long-term anticoagulation are discussed.
...
PMID:Spontaneous tibial artery thrombosis associated with varicella pneumonia and free protein S deficiency. 954 47

The development of promising acute stroke treatments is the fruit of the growing appreciation for the complex biochemical processes within neuronal tissue that commence immediately after the onset of ischemia. These biochemical cascades can be modified either by direct pharmacologic mitigation or by rapid restoration of perfusion and oxygenation. With both interventions, the ischemic tissue can remain viable and regain neurologic function rather than progress to infarction. Today the two major pharmacologic approaches to stroke therapy are neuroprotectants and thrombolytics. Neuroprotectants enable neuronal tissues to tolerate periods of minimal perfusion better, whereas thrombolytics facilitate reperfusion by disrupting the fresh thrombus. Important classes of neuroprotectants include calcium channel antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, benzothiazoles, and free radical scavengers. Pro-urokinase is a potentially important investigational thrombolytic. Ancrod, a defibrinogenating agent, is also currently being evaluated in acute stroke.
...
PMID:The stroke pharmacopeia: promising experimental therapies. 961 94

Oxygen deprivation, as occurs during tissue ischemia, tips the natural anticoagulant/procoagulant balance of the endovascular wall to favor activation of coagulation. To investigate the effects of low ambient oxygen tension on the fibrinolytic system, mice were placed in a hypoxic environment with pO2 < 40 Torr. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) antigen, detected by ELISA, increased in a time-dependent fashion after hypoxic exposure (increased as early as 4 h, P < 0.05 vs. normoxic controls), and were accompanied by an increase in plasma PAI-1 activity by 4 h (P < 0.05 vs. normoxic controls). Northern analysis of hypoxic murine lung demonstrated an increase in PAI-1 mRNA compared with normoxic controls; in contrast, transcripts for both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) decreased under hypoxic conditions. Immunocolocalization studies identified macrophages as the predominant source of increased PAI-1 within hypoxic lung. Using a transformed murine macrophage line, striking induction of PAI-1 transcripts occurred under hypoxic conditions, due to both increased de novo transcription as well as increased mRNA stability. Consistent with an important role of the fibrinolytic system in hypoxia-induced fibrin accumulation, PAI-1 +/+ mice exposed to hypoxia exhibited increased pulmonary fibrin deposition based upon a fibrin immunoblot, intravascular fibrin identified by immunostaining, and increased accumulation of 125I-fibrinogen/fibrin in hypoxic tissue. In contrast, mice deficient for the PAI-1 gene (PAI-1 -/-) similarly exposed to hypoxic conditions did not display increased fibrin accumulation compared with normoxic PAI-1 +/+ controls. Furthermore, homozygous null uPA (uPA -/-) and tPA (tPA -/-) mice subjected to oxygen deprivation showed increased fibrin deposition compared with wild-type controls. These studies identify enhanced expression of PAI-1 as an important mechanism suppressing fibrinolysis under conditions of low oxygen tension, a response which may be further amplified by decreased expression of plasminogen activators. Taken together, these data provide insight into an important potential role of macrophages and the fibrinolytic system in ischemia-induced thrombosis.
...
PMID:Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. 972 60

Patients with refractory angina pectoris and end-stage coronary artery disease represent an increasing clinical problem. Numbers of these patients will increase in the future for improved survival due to effective secondary prevention of coronary artery disease. Next to the evaluation of clinical symptoms non-invasive objective parameters of myocardial ischemia are of major relevance before initiation of alternative treatment modalities and for verification of antiischemic effectiveness. Based on our own experience it can be shown that in these patients testing which is mainly based on the patients physical exercise capacity is only of limited value due to the early occurrence of clinical symptoms. Furthermore diffuse perfusion abnormalities reduce the sensitivity of electrocardiographic and scintigraphic detection of ischemic changes. In contrast indirect measures of ischemia relating to the systolic or diastolic function of the left ventricle like doppler-echocardiography and radionuclide ventriculography seem to be promising approaches. This is confirmed by the results from the application of long-term intermittent urokinase therapy. Long-term intermittent urokinase therapy leads to an absolute enhancement of myocardial perfusion, which makes this approach superior to other medical interventions which are mainly based on a reduction of cardiac work-load.
...
PMID:[Assessment of the anti-ischemic effect in patients with therapy refractory angina pectoris in end-stage coronary heart disease--results of chronic intermittent urokinase therapy]. 982 80


<< Previous 1 2 3 4 5 6 7 8 9 10

---