Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a key component of the plasminogen activation system, uPAR, the receptor for the plasminogen activator of the urokinase type, is involved in many physiological and pathological processes. Besides its classical roles, there has been increased evidence that uPAR or uPAR-associated pathways, participate in the development, in the functioning and in the pathology of the central nervous system. Qualitative and quantitative changes in the expressions of uPAR and of its canonical ligand uPA have been observed in a large variety of epileptic disorders, either in human or in animal models, as well as in other brain diseases (stroke and brain trauma, multiple sclerosis, Alzheimer's disease, cerebral malaria, HIV-associated leukoencephalopathy and encephalitis). The variety of such pathological conditions and the different brain areas and cell types involved, likely reflects the wide range and the complexity of the multiple and somehow intertwined pathophysiological mechanisms related with uPAR. In the mouse, the knock-out of the Upar-encoding gene (Plaur) leads to significant and nearly complete loss in parvalbumin-containing interneurons during brain development. This is associated with increased susceptibility to spontaneous and chemically-induced seizures and with increased anxiety and impaired social interactions. The recent identification of the novel uPAR ligand SRPX2 (Sushi repeat protein, X-linked 2) and the regulation of both the SRPX2 and PLAUR genes by transcription factor FOXP2 has shed novel and exciting insights into the role of uPAR-related molecular networks in rolandic epilepsy, in developmental verbal dyspraxia, in perisylvian polymicrogyria, and generally in disorders of the speech areas and circuits. uPAR, its regulators and partners, as well as other proteins containing Ly-6/uPAR/alpha-neurotoxin domains, represent key entry points for present and future studies not only on speech-related disorders but also on epilepsy and autism spectrum disorders.
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PMID:The role of the urokinase receptor in epilepsy, in disorders of language, cognition, communication and behavior, and in the central nervous system. 2171 Dec 33

Thrombolytic therapy by infusion of analogs of tissue plasminogen activator (tPA), other recombinant-based plasminogen activators (e.g., alteplase, reteplase, and tenecteplase), streptokinase, and urokinase (uPA) aims to clear blood clots and restore blood flow in occluded blood vessels. Thrombolytic therapy is thereby frequently used in patients with myocardial infarction, stroke, peripheral arterial disease, and massive pulmonary embolism. The leading drawbacks of thrombolysis and associated therapy are represented by a significant burden of inefficacy combined with a high risk of bleeding complications. Recent advances in understanding the complex pathophysiology of vascular occlusions, combined with important technological innovations, are notably improving the therapeutic armamentarium against thrombotic and occlusive disorders. Most of the past and ongoing research in this area have entailed thrombus-targeted fibrinolytic therapy with either tissue- and fibrin-specific immunoconjugates, fibrinolytic-bearing erythrocytes, or fibrinolytic-bearing nanoparticles. The greatest advantages of thrombus-targeted fibrinolysis, especially with biocompatible nanoparticles, are represented by their preferential localization within developing clots, effectual thrombolysis and enhanced safety due to substantial reduction of the dosage of fibrinolytic agents, and reduced onstream adverse effects. These positive biological features, coupled with minimal extravasation and favorable clearance from the circulation, appear advantageous for obtaining more efficacious and durable thrombolytic effects while concomitantly lowering or even eliminating the risk of systemic bleeding complications that typically accompany the injection of free or soluble plasminogen activators. Although an ideal technique has not been definitely established so far, tPA-bearing nanoparticles exhibiting affinity for clot-specific cells and biomolecules coupled with low-frequency ultrasound seem to bear the greatest advantages for prevention and therapy of acute thrombosis, with the possibility to specifically guide and concentrate the thrombolytic agent at the site of pathologic thrombi and clear preexisting clots by a series of mechanisms combining mechanical stress and increased penetration and effectiveness of the drugs employed.
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PMID:Novel and emerging therapies: thrombus-targeted fibrinolysis. 2303 25

Medium optimization is an important strategy that can lead to several fold increase in the production of proteins in cell culture. However, the usual methods of medium optimization are complex and time consuming. Urokinase is a widely employed thrombolytic drug for the treatment of stroke. We describe here medium optimization for maximizing urokinase production by HT-1080 cells using supplementation of specific amino acids. The new specifically designed method resulted in 240 % increase in urokinase productivity.
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PMID:Amino acid supplementation enhances urokinase production by HT-1080 cells. 2467 68

Intraventricular hemorrhage (IVH) is the most severe form of stroke with intraventricular fibrinolysis (IVF) as a hopeful treatment. Urokinase (uPA) and tissue-type plasminogen activator (tPA) are used for IVF in Human. No clinical trial has evaluated the differential impact of these two fibrinolytics for IVF. Thus, we decided here to compare the use of these two fibrinolytics in a pre-clinical study. IVH was induced in rats by injection of collagenase type VII within the brain parenchyma followed by an IVF. Rats were randomized to receive uPA, tPA or saline within the ventricle, and cerebrospinal fluid was aspirated. Hematoma and ventricular volumes, brain water contents, inflammation and neurological deficits were measured at day three post-treatments. We also performed in vitro studies, in which neuronal cultures were subjected to an excitotoxic paradigm in the presence of either uPA or tPA. In the IVH model, we showed that although both uPA and tPA led to reduced ventricular volumes, only uPA significantly improved functional recovery. These results could be explained by the fact that uPA, in contrast of tPA, fails to promote inflammatory processes and neurotoxicity. Our study provides evidence supporting the use of uPA for fibrinolysis of IVH. A clinical trial could be warranted if tPA failed to improve outcomes in human IVH.
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PMID:Urokinase versus Alteplase for intraventricular hemorrhage fibrinolysis. 2484 2


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