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

The neuropathies associated with infectious processes, including leprosy, retroviral infections and Chagas' disease, represent the largest group of neuropathies in the world. Segmental demyelination and axonal degeneration of nerve fibres are associated with inflammatory infiltrates which contain a large number of mononuclear phagocytes. In order to learn more about the role played by macrophage activation in the nerve lesions observed in inflammatory neuropathies, we have performed a morphological study of nerves injected with products of activation of macrophages including proteolytic enzymes and cytokines (tumour necrosis factor and alpha beta-interferon). We have also studied the effects on nerve fibres of macrophages activated by ingestion of proteose-peptone, a foreign protein, and in the course of a delayed-type hypersensitivity (DTH) reaction. We have found that proteases and urokinase were potent demyelinating agents and that activated macrophages were also able to induce significant demyelination of neighbouring fibres. In contrast, injection of TNF alpha induced more severe nerve lesions consisting of axonal degeneration of the majority of nerve fibres. We thus conclude that infected macrophages which penetrate the endoneurium and macrophages activated in a DTH reaction can both cause neuropathy.
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PMID:Nerve lesions induced by macrophage activation. 145 50

A case of femoral neuropathy from iliac muscle hematoma occurring in a patient treated with urokinase, subcutaneous heparin and aspirin for myocardial infarction is reported. Diagnosis of this complication was suspected on the basis of clinical signs and on the fact that the patient had received anticoagulants. Computed tomography allowed direct and clear visualization of the hematoma. Anticoagulant suspension followed by an early surgical decompression seems to be the ideal treatment for this neuropathy; however, our patient died for a reinfarction after stopping heparinic administration. This may indicate that, in some patients "at risk", it is better to reduce rather than stop anticoagulant therapy.
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PMID:Femoral nerve palsy secondary to anticoagulant induced iliacus hematoma. A case report. 217 52

Catheter-directed thrombolysis was used either alone or as an adjunct to percutaneous transluminal angioplasty (PTA) or surgery for peripheral vascular occlusion on 112 occasions in 102 patients. Symptom duration ranged from < one to > twenty-eight days. Thrombolytic therapy using urokinase plasminogen activator thrombolysis (uPAT), including intrathrombic injection when possible, was successful (> 50% lysis) in 99 procedures (88%). Technical failure (< 50% lysis) occurred in 13 procedures (12%). In 9 of the 13 failures, intrathrombic injection of urokinase was not possible, but the duration of occlusion was > twenty-eight days in all but 1. Two other failures were from embolic sources and 2 more occurred in patients with a hypercoagulable state. The uPAT was adjunctive to PTA/surgery in 56 cases (50%). PTA following uPAT was required and successfully performed in 24 of 27 cases (88.9%). Surgery followed lytic therapy in another 32 (including the 3 failed PTAs). In the remaining 56 cases (50%), no additional intervention was required. There were 20 complications (18%), minor in 16 of 20 (80%). Minor complications included small puncture site hematomas and distal embolization resolved by continued lytic therapy. Four major complications occurred. One was retroperitoneal hemorrhage directly contributing to the only death in the series. The other 3 were hematuria (2) and femoral neuropathy (1). The authors conclude that catheter-directed lytic therapy alone or as an adjunct to PTA/surgery is a valuable approach to peripheral vascular thromboembolic disease. It is less likely to succeed in chronic occlusion. The incidence of complications is moderate but acceptable.
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PMID:Catheter-directed urokinase thrombolysis: an adjunct to PTA/surgery for management of lower extremity thromboembolic disease. 794 36

Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired. Despite the awareness of this angiogenic paradox, many questions remain unanswered. This review aims at highlighting the different microvascular and macrovascular complications that are often concurrent in diabetic patients. A revision of the recent findings published in the literature regarding the angiogenic paradox will be performed. Apparently, endothelial dysfunction, as well as molecules such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) play a major role in diabetic vascular complications. Specific tissues with impaired angiogenesis exhibit microenvironment features, such as increased PAI-1/uPA ratio and decreased blood flow, whereas TGFbeta increases extracellular matrix deposition, preventing the vascularization process. In addition, the monocytes/macrophages are important in endothelium activation for arteriogenesis and its arteriogenic response is reduced, leading to impaired collateral artery growth. Moreover, molecular mechanisms involved will be addressed, including abnormalities in growth factor, cytokines and metabolic derangements.
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PMID:Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. 2360 39