Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients with severe intraventricular hemorrhage (IVH) were treated using urokinase administered into the lateral ventricles via a ventricular drainage catheter. All patients were female and of ages ranging from 24 to 53 years. The primary diseases were hemorrhagic infarction, moyamoya disease, sinus thrombosis, and thalamic bleeding. Urokinase administration was initiated at 1.3 days average after occurrence of IVH and continued for 3.3 days average in doses of 12,000-96,000 IU per day. Average clot lysis times from IVH, as assessed by computed tomography, were 5.0 +/- 0.8, 5.0 +/- 1.4, and 6.0 +/- 0.8 days for the fourth, the third, and the lateral ventricles, respectively. All patients suffered from meningitis which was probably caused by urokinase administration through a ventricular catheter. However, this was successfully treated by changing the antibiotics. There was no general bleeding tendency or intraventricular rebleeding due to urokinase administration, and none of the ventricular catheters were obstructed by clots throughout the course. The final outcome was good recovery in two patients, severe disability in one, and persistent vegetative state in one. These results correlated well with the consciousness level seen before ventricular drainage in each patient. Consequently, we are convinced that urokinase administration can prevent the harmful effects of IVH and that urokinase is useful not only for lysing ventricular clots but also for maintaining the patency of the ventricular catheter, which is important for control of intracranial pressure in the acute stage of severe IVH.
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PMID:Treatment of intraventricular hemorrhage using urokinase. 169 49

The authors report the results of a retrospective review, between January 1986 and December 1991, of the results of early surgery and intrathecal thrombolytic therapy in 111 patients with aneurysmal subarachnoid hemorrhage. Effects on clot lysis, angiographic and symptomatic vasospasm, cerebral infarction, and clinical outcome were compared in 60 patients treated with urokinase (UK) 60,000 IU/d for 7 days (UK group), 22 patients treated with 0.042 to 1 mg tissue plasminogen activator (tPA) every 6 to 8 hours for 5 days (tPA group), and 29 patients who did not receive treatment with either thrombolytic agent (no-treatment group). The no-treatment group consisted of all patients treated before July 1986 and of patients in whom thrombolytic therapy was attempted but failed to start or in whom the therapy was not used intentionally because of small subarachnoid clot. Treatment with UK was employed between July 1986 and March 1991, and tPA was employed during the remainder of the study for patients at a higher risk for vasospasm. The severity of angiographic vasospasm and the incidence of infarction in the UK and the tPA groups were less than those of the no-treatment group (P < 0.01), in spite of a larger amount of initial subarachnoid blood clot in both thrombolytic groups. This appears to be the result of the more rapid clearance of cisternal clot in the thrombolytic groups than the no-treatment group (P < 0.01). Only tPA therapy reduced the incidence of symptomatic vasospasm (P < 0.05). No serious complications were observed, although in the tPA group, asymptomatic intraventricular hemorrhage occurred in one patient, and transient confusion in another. Both received 4 mg tPA/d. Meningitis was suspected in 16 patients of the UK group. However, in this relatively small retrospective series, there were no differences among the three groups in overall outcome at 3 months. This study indicates that postoperative intrathecal thrombolytic therapies, especially with less than 4 mg/d of tPA, are effective in lysing subarachnoid clot and preventing vasospasm and infarction safely.
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PMID:Vasospasm prevention with postoperative intrathecal thrombolytic therapy: a retrospective comparison of urokinase, tissue plasminogen activator, and cisternal drainage alone. 817 83

The use of cisternal drainage can lead to complications such as shunt-dependent hydrocephalus and meningitis. We assessed the indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The SAH scores by CT on admission and on the day after surgery were used to evaluate two parameters: the total amount of subarachnoid blood on admission and the clearance rate of subarachnoid blood by surgery. In patients whose parameters values belonged to the range where the total SAH score on admission exceeded 10 points and the surgical clearance rate was less than 50%, the possibility of cerebral infarction was significantly higher in patients without than in those with irrigation (p < 0.05). However, there was no difference between patients with and without irrigation for parameter values outside of the range. Therefore, this range may be useful in providing stricter indications for irrigation therapy with urokinase and thus avoiding the complications of cisternal drainage.
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PMID:Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage. 892 7

The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent meningitis, 63 had lymphocytic meningitis, 12 had encephalitis, and 54 patients were suspected of, but had no evidence of, meningitis. There was a significant difference in suPAR levels among patient groups (Kruskal Wallis test, p < 0.0001) with significantly higher CSF suPAR levels in patients with CNS infection (purulent meningitis: median suPAR 2.41 microg/l (range 0.12-35), lymphocytic meningitis: 1.10 microg/l (0.15-5.31), and encephalitis (1.77 microg/l (0.17-11.7)) than in patients without meningitis (0.64 microg/l (0-5.34) (Dunn's multiple comparison test, p < 0.05). Also, patients with purulent meningitis had significantly higher CSF suPAR levels than patients with lymphocytic meningitis (p < 0.001). Patients with purulent meningitis who died (n = 8, 4.9 microg/l (1.3-35) had significantly higher CSF levels of suPAR than patients who survived (n = 46, 2.1 microg/l (0.1-24), Mann Whitney, p = 0.046). Employing a cut-off point of 3.1 and above, the OR (95%CI) for fatal outcome was 11.9 (1.4-106), univariate logistic regression analysis, p = 0.026. In conclusion, CSF suPAR levels may be an important predictor for fatal outcome in purulent meningitis.
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PMID:Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. 1500 May 53

A hallmark of parasitic meningitis is the infiltration of eosinophils into the subarachnoid space. Infection with Angiostrongylus cantonensis in mice induced proteinase activity in parallel with the pathological changes of eosinophilic meningitis. Zymogram analysis demonstrated that 70 and 55 kDa proteinases from cerebrospinal fluid (CSF) were active against the casein/plasminogen substrate. The proteinase activities were clearly inhibited by phenylmethanesulphonyl fluoride but not by ethylenediamine tetraacetic acid, 1,10-phenanthroline or leupeptin. Western blotting confirmed these enzymes to be tissue-type plasminogen activator and urokinase-type plasminogen activator, respectively. High activities of tissue-type plasminogen activator and urokinase-type plasminogen activator were detected in the CSF of mice with eosinophilic meningitis, and correlated positively with CSF eosinophil numbers and total protein, respectively. Immunohistochemistry demonstrated that tissue-type plasminogen activator and urokinase-type plasminogen activator localised in the endothelial cells of blood vessels, in blood clots and in infiltrated leukocytes. These results suggest that tissue-type plasminogen activator and urokinase-type plasminogen activator may be play a role in the pathogenesis of eosinophilic meningitis of angiostrongyliasis.
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PMID:Elevation of plasminogen activators in cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis. 1554 96

Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) have been suggested to play an important role in inflammatory diseases. Increased levels of tPA, uPA, uPA receptor (uPAR), and their inhibitor, plasminogen activator inhibitor (PAI)-1, have been found in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. Here, we show that expression of tPA, uPA, uPAR, PAI-1, and PAI-2 is up-regulated during experimental pneumococcal meningitis. In uPAR-deficient mice, CSF pleocytosis was significantly attenuated 24 h after infection, compared with that in infected wild-type (wt) mice. Lack of uPAR did not influence blood-brain barrier permeability, intracranial pressure, expression of chemokines (keratinocyte-derived cytokine and macrophage inflammatory protein-2), bacterial killing, or clinical outcome. No differences in pathophysiological alterations were observed in tPA-deficient mice, compared with those in infected wt mice. These results indicate that uPAR participates in the recruitment of leukocytes to the CSF space during pneumoccal meningitis.
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PMID:Urokinase-type plasminogen activator receptor regulates leukocyte recruitment during experimental pneumococcal meningitis. 1568 95

Infections caused by Streptococcus suis, a major swine pathogen, include meningitis, arthritis, pneumonia and septicaemia. In this study, we investigated interactions that may occur between human brain microvascular endothelial cells (HBMEC), the main constituent of the blood-brain barrier, and S. suis. We show that S. suis acquires plasmin activity in a time-dependent manner when in contact with cultured HBMEC. Cell-associated plasmin activity reached a plateau following a 48h co-incubation period. Zymography analysis revealed that HBMEC produce urokinase, which is probably involved in activation of plasminogen bound to S. suis. We also show that a S. suis culture supernatant which possesses both phospholipase C and haemolysin (suilysin) activities was able to induce the release of arachidonic acid from the membrane of HBMEC. Evidence suggests that the action of suilysin on HBMEC may be a prerequisite for the action of additional molecules such as phospholipase C. These new biological effects associated with S. suis may play an important role in the migration of S. suis through the blood-brain barrier and in the modulation of local inflammation.
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PMID:Acquisition of plasmin activity and induction of arachidonic acid release by Streptococcus suis in contact with human brain microvascular endothelial cells. 1618 70

Angiostrongyliasis is one of the common causes leading to eosinophilic meningitis. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) may play a role in the pathogenesis. Administration of steroid drugs has been reported to possibly relieve the symptoms of eosinophilic meningitis. This study evaluates the curative effects of albendazole-dexamethasone co-therapy on eosinophilic meningitis in BALB/c mice. Assay indicators for the therapeutic effect include worm recovery, histopathological score of meningitis, tPA, uPA, total protein, and leukocyte counts. The results show that the albendazole-dexamethasone co-therapy significantly decreased (P<0.05) these factors after treatment on day 5 post-inoculation (PI), in contrast to treatment on 15 PI. Thus, the timing of medication is important and is closely related to the anthelmintic efficacy of a drug. At the same dosage and days post-infection, the earlier administration shows better results. This study showed that albendazole-dexamethasone co-therapy is an effective approach for the treatment of parasitic meningitis.
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PMID:Angiostrongylus cantonensis: efficacy of albendazole-dexamethasone co-therapy against infection-induced plasminogen activators and eosinophilic meningitis. 1641 5

Blood-central nervous system (blood-CNS) barrier breakdown, an important pathophysiological event in meningitis, results in extravasation of leucocytes into subarachnoid space. The blood-CNS barrier disruption is mediated by primarily two enzyme systems, the plasminogen activators (PAs) and matrix metalloproteinases (MMPs). The present study showed that the activities of tissue-type PA (tPA), urokinase-type activator (uPA) and MMP-9 in cerebrospinal-like fluid (CSF-like fluid) were significantly increased in mice with eosinophilic meningitis compared with uninfected mice. Eosinophilia significantly correlated with tPA, uPA and MMP-9 activities, and albumin concentration. In addition, when GM6001, a specific matrix metalloproteinase blocker, was injected into infected mice, MMP-9 activity and total protein concentrations declined from their preinjection highs. These results suggest that the PAs and MMP-9 proteolytic cascade may be associated with blood-CNS barrier disruption in eosinophilic meningitis caused by Angiostrongylus cantonensis.
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PMID:Association of plasminogen activators and matrix metalloproteinase-9 proteolytic cascade with blood-CNS barrier damage of angiostrongyliasis. 1662 55

The effects of albendazole and Yin-Chen-Extract co-therapy on Angiostrongylus cantonensis-induced eosinophilic meningitis in BALB/c mice were evaluated. Assay indicators for the therapeutic effect include worm recovery, histopathological score of the fourth ventricle, tissue-type plasminogen activator, urokinase-type plasminogen activator, matrix metalloproteinase-9, cerebrospinal fluid total protein, leukocyte counts, and proinflammatory cytokines. As a result, albendazole and Yin-Chen-Extract co-therapy significantly decreased (P < 0.05) these factors. Although Yin-Chen-Extract may possess pharmacologic activities beneficial to the inhibition of parasite-induced inflammation, many of these hypothetical benefits await scientific testing and confirmation before application. This study suggests that the combination of Yin-Chen-Extract and albendazole has synergistic effects in managing eosinophilic meningitis or eosinophilic meningoencephalitis.
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PMID:Chinese herbal medicine Yin-Chen-Extract as an adjunct to anthelmintic albendazole used against Angiostrongylus cantonensis-induced eosinophilic meningitis or meningoencephalitis. 1696 41


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