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Tissue plasminogen activator

Alexandra J Sequeira, Michael G Fara, Ariane Lewis
Tissue plasminogen activator (tPA) is administered to patients with suspected ischemic stroke to improve blood flow to the brain In rare cases, patients present with complaints of stroke symptoms that appear to be non-organic due to malingering, factitious disorder, or conversion disorder (psychogenic stroke mimics). Deciding whether or not to administer tPA to these patients can be challenging. The risk of hemorrhage after administration of tPA is low, but not zero. The ethical principles of beneficence and nonmaleficence need to be weighed carefully in these situations...
2018: Journal of Clinical Ethics
Choi Yi Li, Simon J de Veer, Ruby H P Law, James C Whisstock, David Craik, Joakim E Swedberg
Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are two serine proteases that contribute to initiating fibrinolysis by activating plasminogen. uPA is also an important tumour-associated protease due to its role in extracellular matrix remodelling. Overexpression of uPA has been identified in several different cancers and uPA inhibition has been reported as a promising therapeutic strategy. Although several peptide-based uPA inhibitors have been developed, the extent to which uPA tolerates different tetrapeptide sequences that span the P1-P4 positions remains to be thoroughly explored...
September 17, 2018: Chembiochem: a European Journal of Chemical Biology
Xianhua Wu, Yongsheng Gong, Xuebing Ding, Gang Cheng, Weiya Yan, Xiaowei She, Changxing Wang, Xia Li
Tissue-type plasminogen activator (tPA) is involved in the lysis of blood clots. In this study, we attempted to target thrombolysis and enhance blood clot lysis by generating a construct (pLEGFP-N1-tPA) to integrate tPA gene into the genome of different cell lines. pLEGFP-N1-tPA construct was generated and used to target the tPA gene in different cell lines. The thrombolytic effects mediated by the supernatant from transfected HeLa cells and Linx cells were assessed using plasma thrombus plates. Furthermore, enhanced green fluorescent protein (EGFP), which was fused to the tPA gene in the pLEGFP-N1-tPA construct, was analyzed under the fluorescent microscope to assess tPA localization...
September 14, 2018: Biochemical Genetics
Wan-Qian Ge, Jie Chen, Hong Pan, Fei Chen, Cheng-Ye Zhou
BACKGROUND: The purpose of this study was to analyze the risk factors of hemorrhagic transformation (HT) after intravenous thrombolysis using a recombinant tissue plasminogen activator (r-tPA) in acute ischemic stroke (AIS). METHODS: We included 199 consecutive patients in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to October 2017 with a diagnosis of AIS. The patients were divided into 2 groups: HT and non-HT. The related risk factors were recruited before and after receiving r-tPA thrombolysis...
September 11, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Fan Zhang, Jie Luo, Xianlin Zhu
Some studies have indicated that ketamine has a rapid antidepressant effects, but the underlying molecular mechanism is still unclear. Researchers have found that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are related to depression; they elicit opposite effects on cellular functions. It is clear that tissue plasminogen activator (tPA) is a key regulatory element in the conversion of proBDNF to mBDNF. The chronic unpredicted mild stress (CUMS) procedure is a classical and reliable method to establish the model of depression...
August 20, 2018: Psychiatry Research
Barak Bar, Jose Biller
Remarkable advances have occurred in the management of acute ischemic stroke especially in regards to reperfusion treatments. With advances in reperfusion treatments come the risk of complications associated with these treatments. Areas covered: The paper focuses on three acute complications that can occur in the setting of acute ischemic stroke: cerebral edema, hemorrhagic transformation, and orolingual angioedema following administration of alteplase, a recombinant tissue plasminogen activator. Predictors of the development of these complications are reviewed...
September 14, 2018: Expert Review of Neurotherapeutics
Sachiko Shioya, Takeshi Masuda, Tadashi Senoo, Yasushi Horimasu, Shintaro Miyamoto, Taku Nakashima, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
Radiation-induced pulmonary fibrosis is a serious complication. Plasminogen activator inhibitor-1 (PAI-1) has been indicated to be a key factor in the progression of pulmonary fibrosis. In the present study, the effect of PAI-1 deficiency on radiation-induced pulmonary fibrosis was analyzed. Wild-type (WT) and PAI-1 -deficient (PAI-1-/- ) mice were treated with thoracic irradiation of 15 Gy to induce pulmonary fibrosis. Analyses of bronchoalveolar lavage (BAL) fluids were performed 0, 4, 12, 18, and 24 weeks after irradiation...
October 2018: Experimental and Therapeutic Medicine
Fan Gao, Chen Chen, Jun Lyu, Jie Zheng, Xian-Cang Ma, Xing-Yun Yuan, Kang Huo, Jian-Feng Han
Purpose: The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. Patients and methods: Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study...
2018: Neuropsychiatric Disease and Treatment
Elodie Ong, Omer Eker, Leila Chamard, Tae Hee Cho, Laurent Derex, Marielle Buisson, Laura Mechtouff, Yves Berthezene, Norbert Nighoghossian
BACKGROUND AND PURPOSE: Transient ischemic attack may rarely reveal an intracranial artery occlusion. We analyzed acute magnetic resonance imaging (MRI) patterns and early outcome after reperfusion therapy in these cases. METHOD: Clinical and imaging data were taken retrospectively from our comprehensive stroke center registry. Two MRI patterns were determined. Pattern A: full mismatch with negative diffusion-weighted imaging (DWI) and perfusion defect. Pattern B: large mismatch with positive DWI and perfusion defect...
September 12, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
Li-Rong Yu, Jinchun Sun, Jaclyn R Daniels, Zhijun Cao, Laura Schnackenberg, Devasmita Choudhury, Paul M Palevsky, Jennie Z Ma, Richard D Beger, Didier Portilla
Introduction: Currently, no effective therapies exist to reduce the high mortality associated with dialysis-dependent acute kidney injury (AKI-D). Serum biomarkers may be useful in understanding the pathophysiological processes involved with AKI and the severity of injury, and point to novel therapeutic targets. Methods: Study day 1 serum samples from 100 patients and day 8 samples from 107 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the slow off-rate modified aptamers scan proteomic platform to profile 1305 proteins in each sample...
September 2018: KI Reports
Susan B Fowler, Christian A Rosado, Jennifer Jones, Suzanne Ashworth, Darlene Adams
INTRODUCTION: Despite the increasing incidence of acute ischemic stroke in the United States, many health care facilities remain unprepared to manage patients with acute stroke, including the administration of intravenous alteplase (recombinant tissue plasminogen activator [rTPA]). This has led to an opportunity for telemedicine systems to facilitate these evaluations and acute medical stroke treatment decisions. However, even telemedicine systems can fail to provide timely evaluation and management of the patient with acute stroke...
September 5, 2018: Journal of Emergency Nursing: JEN: Official Publication of the Emergency Department Nurses Association
Jacek M Kwiecien
As the systematic work on the pathogenesis of the white matter injury in the spinal cord models progresses, it becomes obvious that a severe and extraordinarily protracted, destructive inflammation follows the initial injury. Appropriate anti-inflammatory therapies of sufficient duration should not only inhibit but also lead to the elimination of this destructive inflammation, thus resulting in neuroprotection of the spinal cord tissue and a greater preservation of the neurologic function. While dexamethasone, a powerful, anti-inflammatory steroid analog administered continuously by subdural infusion for 7 days inhibited severe macrophage infiltration in the cavity of injury, the dose used was remarkably toxic...
2018: Methods in Molecular Biology
Jiangnan Hu, Shengwei Huang, Lu Zhu, Weijie Huang, Yiping Zhao, Kunlin Jin, Qichuan ZhuGe
Tissue plasminogen activator (tPA) is the only FDA approved thrombolytic drug for acute ischemic stroke but concerns regarding its limitations remain. Here, we developed a new strategy by incorporating tPA into porous magnetic iron oxide (Fe3 O4 )-microrods (tPA-MRs) for targeted thrombolytic therapy in ischemic stroke induced by distal middle cerebral artery occlusion. We showed that intra-arterial injection of tPA-MRs could target the cerebral blood clot in vivo under the guidance of an external magnet, where tPA was subsequently released at the site of embolism...
September 19, 2018: ACS Applied Materials & Interfaces
K K Shahedah, C S Khoo, W Y Wan Nur Nafisah, C F Ng, I Noor Ashikin, M Y Mohd Naim, O Syazarina Sharis, Z Rozman, W Z Wan Asyraf
A 42-year-old female admitted with new-onset atrial fibrillation had a wake-up stroke on the high-dependency unit and the time last seen well (TLSW) was 6.5 h. She suffered left-sided body weakness and her National Institutes of Health Stroke Scale (NIHSS) score was 17. An emergency CT perfusion showed right M1 segment occlusion with more than 50% penumbra. She was given recombinant tissue plasminogen activator (r-tPA) at 9 h from TLSW. An immediate diagnostic angiogram with intention to treat, owing to the presence of large vessel occlusion, showed complete reperfusion after intravenous r-tPA...
September 2018: Journal of the Royal College of Physicians of Edinburgh
Masashi Akamatsu, Futaba Maki, Hisanao Akiyama, Daisuke Hara, Masashi Hoshino, Yasuhiro Hasegawa
BACKGROUND: Rheumatoid meningitis presenting with a stroke-like attack (RMSA) is a rare manifestation of rheumatoid arthritis (RA). When the patients arrive within the time-window for recombinant tissue plasminogen activator (rt-PA) infusion therapy, no diagnostic protocol has been established. CASE PRESENTATION: A 55-year-old woman was brought by ambulance to our hospital with complaints of sudden-onset dysarthria and left arm numbness. The National Institutes of Health Stroke Scale (NIHSS) score was 5, and the Alberta Stroke Program Early CT Score was 8...
September 6, 2018: BMC Neurology
Marcos Takuya Kuroki, Katelynn Ferranti, Faisal Aziz, John Radtka
Patients who have undergone endovascular aneurysm repair (EVAR) need lifelong monitoring because of the risk of aneurysm rupture secondary to delayed endoleaks. Thrombolytic therapy may expose patients with previous EVAR to the risk for development of new endoleaks. We describe a case in which a single dose of intravenous tissue plasminogen activator for acute ischemic stroke was complicated by aneurysm sac expansion secondary to a recurrent endoleak. The potential for a life-threatening complication may warrant routine imaging evaluation of the stent graft after systemic tissue plasminogen activator therapy for acute ischemic stroke in patients with previous EVAR...
September 2018: Journal of Vascular Surgery Cases and Innovative Techniques
Elyar Sadeghi-Hokmabadi, Mohammad Yazdchi, Mehdi Farhoudi, Homayoun Sadeghi, Aliakbar Taheraghdam, Reza Rikhtegar, Hannaneh Aliyar, Sahar Mohammadi-Fallah, Rogayyeh Asadi, Elham Mehdizadeh-Far, Neda Ghaemian
Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment in patients with acute ischemic stroke (AIS); however, due to some serious complications, particularly intracranial hemorrhage (ICH), many physicians are still reluctant to use it liberally. This study sought to find potential prognostic factors in patients with AIS treated with tPA. Methods: A retrospective, hospital-bases observational study was conducted. Consecutively, a total of 132 patients with AIS treated with intravenous tPA, form June 2011 to July 2015 were enrolled...
January 5, 2018: Iranian Journal of Neurology
Hui Chen, Guangming Zhu, Nan Liu, Ying Li, Yonghong Xia
Brain permeability imaging techniques are specific for the assessment of blood-brain barrier integrity. The present review article primarily focuses on the application of permeability imaging in cases of ischemic stroke. The permeability maps may be used to predict future hemorrhagic transformation in patients following acute ischemic stroke, that have been treated with tissue plasminogen activator (tPA) or recanalization therapy. The permeability imaging would help make the clinical decision to administer tPA following acute ischemic stroke or not, which is not only due to the current 3-4...
September 2018: Experimental and Therapeutic Medicine
Bing Wu, Nan Liu, Max Wintermark, Mark W Parsons, Hui Chen, Longting Lin, Shuai Zhou, Gang Hu, Yongwei Zhang, Jun Hu, Ying Li, Zihua Su, Xinhuai Wu, Guangming Zhu
Background and Purpose: Cerebral hemorrhage is a serious potential complication of stroke revascularization, especially in patients receiving intra-arterial tissue-type plasminogen activator (tPA) therapy. We investigated the optimal pre-intervention delay time (DT) of computed tomography perfusion (CTP) measurement to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke (AIS) patients after intra-arterial tissue plasminogen activator (tPA) treatment. Methods: The study population consisted of a series of patients with AIS who received intra-arterial tPA treatment and had CTP and follow-up computed tomography/magnetic resonance imaging (CT/MRI) to identify hemorrhagic transformation...
2018: Frontiers in Neurology
Dan Lu, Hong-Cheng Mai, Yu-Bin Liang, Bing-Dong Xu, An-Ding Xu, Yu-Sheng Zhang
Hemorrhage transformation is the most challenging preventable complication in thrombolytic therapy and is related to recombinant tissue plasminogen activator (rt-PA)-induced blood-brain barrier (BBB) damage. Intraperitoneal injections of normal or high doses of rosuvastatin were administered to Balb/c mice 20 min prior to middle cerebral artery occlusion (MCAO) surgery for 3 h followed by reperfusion with rt-PA thrombolytic therapy and cerebral blood flow monitoring to investigate whether a high or normal dose of rosuvastatin reduces BBB damage after brain ischemia and rt-PA reperfusion...
2018: Frontiers in Pharmacology
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