During focal cerebral ischemia, matrix metalloproteinase-2 (MMP-2) can contribute to the loss of microvessel integrity within ischemic regions by degrading the basal lamina. MMP-2 is secreted in latent form (pro-MMP-2), but the activation of pro-MMP-2 in the ischemic territory has not been shown. Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP-2, MT1-MMP and MT3-MMP, and the indirect activation system tissue plasminogen activator, urokinase (u-PA), its receptor (u-PAR), and its inhibitor PAI-1 after middle cerebral artery occlusion/reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons. The expressions of all three MMPs, u-PA, u-PAR, and PA1-1, but not tissue plasminogen activator, were increased from 1 hour after middle cerebral artery occlusion in the ischemic core. mRNA transcripts confirmed the increases in latent MMP-2, u-PA, u-PAR, and PAI-1 antigen very early after middle cerebral artery occlusion. The expression patterns are consistent with secretion of pro-MMP-2 and its activators in the ischemic core, perhaps from separate cell compartments. The rapid and coordinate appearance of pro-MMP-2 and its activation apparatus suggest that in the primate striatum this protease may participate in matrix injury during focal cerebral ischemia.
logic, and anatomopathologic data presented. Because the first steroid treatment, which was initiated while the patient was still on riluzole, had no lasting effect on his complaints, whereas discontinuation of riluzole combined with steroid treatment improved his condition, we consider the diagnosis of HP caused by riluzole to be probable.The diagnosis of HP should be considered in patients with ALS taking riluzole and presenting with dyspnea, weight loss, and occasionally fever, in association with pulmonary infiltrates and a lymphocytic broncho-alveolar lavage fluid. The HP reaction does not depend on dosage, only on prior sensitization to the agent.
The Reynolds equation, incorporating Elrod’s cavitaton algorithm, is discretized on a rectangular grid in computational space through coordinate mapping in order to accurately analyze a herringbone grooved journal bearing of a spindle motor in a computer hard disk drive. The pressure distribution and cavitation area are determined by using the finite volume method. Predicted results are compared to experimental data of previous researchers. It was found that positive pressure is developed within the converging section of the bearing and that a cavity occurs in the diverging section. Cavitation has been neglected in the previous analyses of the herringbone grooved bearing. Load capacity and bearing torque are increased due to the increase of eccentricity and L/D and the decrease of the groove width ratio. The maximum load capacity was found to occur at a groove angle of 30 degrees while bearing torque remains constant due to the variation of the groove angle. The cavitation region is significantly decreased with the inclusion of herringbone grooves. However, the region increases with the increase of the eccentricity, L/D, groove angle and the rotational speed and the decrease of the groove width ratio. [S0742-4787(00)01401-6]
Background and Purpose-In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. Methods-In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Results-Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. D ual antiplatelet therapy that simultaneously blocks different platelet-activation pathways would more potently inhibit platelet activation and more effectively reduce the risk of ischemic vascular events compared with antiplatelet monotherapy. In contrast to acute coronary syndrome trials, several large stroke trials and a meta-analysis have failed to demonstrate the superior efficacy of dual antiplatelet therapy over antiplatelet monotherapy, but the risk of major bleeding increased with dual antiplatelet therapy. Conclusions-Clopidogrel1-4 Enrolling patients with a lower risk of recurrence and initiating treatment after a high-risk period might account for the failures.CHANCE (Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events) trial and a following meta-analysis showed that clopidogrel plus aspirin versus aspirin alone initiated in early period significantly reduced risk of recurrent stroke without increasing major bleedings. 5,6 However, the CHANCE trial exclusively enrolled Chinese patients who have a higher risk of stroke compared with other populations, and risk factor control for secondary stroke prevention during the trial was inadequate.5 Therefore, it has been on debate whether the findings of the CHANCE trial might be applied to other populations.The risk of recurrent ischemic stroke is high during the early period after stroke onset, and patients with large artery atherosclerosis (LAA) had the highest risk ...
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