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Tissue plasminogen activator

Yoshikazu Sawaguchi, Zuojun Wang
Recombinant tissue-type plasminogen activator (rt-PA) is effective and widely used in the treatment of acute ischemic stroke (AIS). However, symptomatic intracranial hemorrhage (ICH), an adverse reaction of rt-PA, is known to occur depending on underlying diseases and rt-PA doses, and to occur more frequently with a greater delay from stroke onset until initiation of rt-PA. Therefore, limitations on the use of rt-PA, such as having to be started within 4.5 hours of stroke onset, mean that rt-PA is only indicated in some stroke patients...
October 22, 2016: Biological & Pharmaceutical Bulletin
Marie Garraud, Kahina Khacef, Anne-Clémence Vion, Claire Leconte, Min Yin, Jean-Marie Renard, Catherine Marchand-Leroux, Chantal M Boulanger, Isabelle Margaill, Virginie Beray-Berthat
Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved pharmacological strategy for acute ischemic stroke. However, rt-PA exhibits vascular toxicity mainly due to endothelial damage. To investigate the mechanisms underlying rt-PA-induced endothelial alterations, we assessed the role of rt-PA in the generation of endothelial microparticles (EMPs), emerging biological markers and effectors of endothelial dysfunction. The mouse brain-derived endothelial cell line bEnd...
November 15, 2016: Journal of the Neurological Sciences
Joseph S Domino, Jonggyu Baek, William J Meurer, Nelda Garcia, Lewis B Morgenstern, Morgan Campbell, Lynda D Lisabeth
OBJECTIVE: To explore temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center and variation in trends by age, sex, ethnicity, and stroke severity. METHODS: Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study between January 1, 2000, and June 30, 2012. tPA, demographics, and stroke severity as assessed by the NIH Stroke Scale (NIHSS) were ascertained from medical records...
October 21, 2016: Neurology
Estelle Seyman, Hilla Shaim, Shani Shenhar-Tsarfaty, Tali Jonash-Kimchi, Natan M Bornstein, Hen Hallevi
BACKGROUND: Acute ischemic stroke (AIS) is a common neurological event that causes varying degrees of disability. AIS outcome varies considerably, from complete recovery to complete loss of tissue and function. This diversity is partly explained by the compensatory ability of the collateral circulation and the ensuing cerebral flow grade. The collateral flow to the anterior circulation largely supplies the cortical areas. The deep brain tissue is supplied by penetrating arteries and has little or no collateral supply...
October 21, 2016: BMC Neurology
Dong-Eog Kim, Jeong-Yeon Kim, Su-Kyoung Lee, Ju Hee Ryu, Ick Chan Kwon, Cheol-Hee Ahn, Kwangmeyung Kim, Dawid Schellingerhout
Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of stroke than relying on indirect measurements, and will be a potent and robust vascular research tool. We use an optical imaging approach that labels thrombi with a molecular imaging thrombus marker - a Cy5.5 near-infrared fluorescent (NIRF) probe that is covalently linked to the fibrin strands of the thrombus by the fibrin-crosslinking enzymatic action of activated coagulation factor XIIIa during the process of clot maturation...
September 25, 2016: Journal of Visualized Experiments: JoVE
Emiliano Tognoli, Matte Leoni, Daniele Morelli, Elisa Sottotetti, Antonia Martinetti, Stefano Signoroni, Carlotta Galeone, Gianfranco Gallino
Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up-regulation of the urokinase-type plasminogen activator system and a spillover of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared to a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p=0...
October 19, 2016: Wound Repair and Regeneration
Joan Montaner, Alejandro Bustamante, Silvia García-Matas, Maite Martínez-Zabaleta, Carmen Jiménez, Javier de la Torre, Francisco R Rubio, Tomás Segura, Jaime Masjuán, David Cánovas, Mar Freijo, Raquel Delgado-Mederos, Javier Tejada, Aida Lago, Yolanda Bravo, Natália Corbeto, Dolors Giralt, Bárbara Vives-Pastor, Anna de Arce, Francisco Moniche, Pilar Delgado, Marc Ribó
BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days...
October 6, 2016: Stroke; a Journal of Cerebral Circulation
Kévin Ly, Rachid Essalmani, Roxane Desjardins, Nabil G Seidah, Robert Day
The mechanism of LDL receptor (LDLR) degradation mediated by the proprotein convertase subtilisin/kexin type 9 (PCSK9) has been extensively studied, however many steps within this process remain unclear and still require characterization. Recent studies have shown that PCSK9 lacking its Cys/His-rich domain can still promote LDLR internalization, but the complex does not reach the lysosome suggesting the presence of an additional interaction partner(s). In the present study we carried out an unbiased screening approach to identify PCSK9 interacting proteins in the HepG2 cells' secretome using co-immunoprecipitation combined with mass spectrometry analyses...
October 7, 2016: Journal of Biological Chemistry
John H Griffin, Laurent O Mosnier, José A Fernández, Berislav V Zlokovic
APC (activated protein C), derived from the plasma protease zymogen, is antithrombotic and anti-inflammatory. In preclinical injury models, recombinant APC provides neuroprotection for multiple injuries, including ischemic stroke. APC acts directly on brain endothelial cells and neurons by initiating cell signaling that requires multiple receptors. Two or more major APC receptors mediate APC's neuroprotective cell signaling. When bound to endothelial cell protein C receptor, APC can cleave protease-activated receptor 1, causing biased cytoprotective signaling that reduces ischemia-induced injury...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Sandy Middleton, Chris Levi, Simeon Dale, N Wah Cheung, Elizabeth McInnes, Julie Considine, Catherine D'Este, Dominique A Cadilhac, Jeremy Grimshaw, Richard Gerraty, Louise Craig, Verena Schadewaldt, Patrick McElduff, Mark Fitzgerald, Clare Quinn, Greg Cadigan, Sonia Denisenko, Mark Longworth, Jeanette Ward
BACKGROUND: Internationally recognised evidence-based guidelines recommend appropriate triage of patients with stroke in emergency departments (EDs), administration of tissue plasminogen activator (tPA), and proactive management of fever, hyperglycaemia and swallowing before prompt transfer to a stroke unit to maximise outcomes. We aim to evaluate the effectiveness in EDs of a theory-informed, nurse-initiated, intervention to improve multidisciplinary triage, treatment and transfer (T(3)) of patients with acute stroke to improve 90-day death and dependency...
October 18, 2016: Implementation Science: IS
Wenning Li, Wen Chen, Maowei Xie, Haiyang Huang, Huiluan Su, Hui Han, Daofa Zhang, Ying Zhang, Xiaohong Yang, Wentan Xu, Yan Su, Wei Wu, Yun Huang, Keying Fu, Jiali Wei
Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA...
October 19, 2016: Renal Failure
Mohammed Ali Khan, Abtin Shahlaee, Alok S Bansal, Joseph I Maguire
PURPOSE: To describe a surgical technique for fluorescein-assisted subretinal tissue plasminogen activator delivery during pars plana vitrectomy for submacular hemorrhage. METHODS: Retrospective, interventional, consecutive case series. RESULTS: Six eyes of 6 patients were reviewed. Etiology of submacular hemorrhage was age-related macular degeneration in 2 eyes and polypoidal choroidal vasculopathy in 4 eyes. Twenty-three-gauge pars plana vitrectomy was performed and fluorescein-stained tissue plasminogen activator was injected in the subretinal space through a 41-gauge cannula in all eyes...
October 11, 2016: Retina
Nermina Buljubasic, K Martijn Akkerhuis, Jin M Cheng, Rohit M Oemrawsingh, Hector M Garcia-Garcia, Sanneke P M de Boer, Evelyn Regar, Robert-Jan M van Geuns, Patrick W J C Serruys, Eric Boersma, Isabella Kardys
OBJECTIVE: The aim of this study was to provide additional insight into the role of fibrinogen in coronary artery disease by investigating the associations between plasma fibrinogen with both degree and composition of coronary atherosclerosis as determined by virtual histology-intravascular ultrasound. PATIENTS AND METHODS: In 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris, preprocedural blood samples were drawn for fibrinogen, C-reactive protein (CRP), interleukin-6, and plasminogen activator inhibitor-1 measurements, and virtual histology-intravascular ultrasound of a nonculprit coronary artery was performed...
October 14, 2016: Coronary Artery Disease
Daniel F Hanley, Richard E Thompson, John Muschelli, Michael Rosenblum, Nichol McBee, Karen Lane, Amanda J Bistran-Hall, Steven W Mayo, Penelope Keyl, Dheeraj Gandhi, Tim C Morgan, Natalie Ullman, W Andrew Mould, J Ricardo Carhuapoma, Carlos Kase, Wendy Ziai, Carol B Thompson, Gayane Yenokyan, Emily Huang, William C Broaddus, R Scott Graham, E Francois Aldrich, Robert Dodd, Cristanne Wijman, Jean-Louis Caron, Judy Huang, Paul Camarata, A David Mendelow, Barbara Gregson, Scott Janis, Paul Vespa, Neil Martin, Issam Awad, Mario Zuccarello
BACKGROUND: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany...
November 2016: Lancet Neurology
Matthew J Flick, Thomas H Bugge
The cell surface orchestrates plasminogen activation through the concomitant binding of plasminogen and plasminogen activators to specific receptors. In this issue, Miles and colleagues describe their detailed phenotypic characterization of mice deficient in Plg-RKT , a key plasminogen receptor expressed in numerous tissues, but highly expressed by proinflammatory macrophages. The analysis provides critical and surprising new insights into the biology of this receptor. This article is protected by copyright...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Nari Choi, Jee-Eun Yoon, Byoung-Won Park, Won-Ho Chang, Hyun-Jo Kim, Kyung Bok Lee
We report a case of aortic dissection masquerading as acute ischemic stroke followed by intravenous thrombolysis. A 59-year-old man presented with dizziness. After examination, the patient had a seizure with bilateral Babinski signs. Soon after identifying multiple acute infarctions in both hemispheres on diffusion-weighted brain magnetic resonance (MR) imaging, tissue plasminogen activator (t-PA) was administered. Both common carotid arteries were invisible on MR angiography, and subsequent chest computed tomography revealed an aortic dissection...
October 2016: Korean Journal of Thoracic and Cardiovascular Surgery
Li-Hong Shou, Dan Cao, Xiao-Hui Dong, Qiu Fang, Bao-Lian Xu, Ju-Ping Fei
<strong>Objective</strong> To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. <strong>Methods</strong> uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively...
September 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
Jongseong Kim, Jung E Park, Matthias Nahrendorf, Dong-Eog Kim
There is an emergent need for imaging methods to better triage patients with acute stroke for tissue-plasminogen activator (tPA)-mediated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thromboemboli. Currently, magnetic resonance (MR) or computed tomography (CT) angiography visualizes the obstruction of blood flow within the vessel lumen rather than the thrombus itself. The present visualization method, which relies on observation of the dense artery sign (the appearance of cerebral thrombi on a non-enhanced CT), suffers from low sensitivity...
September 2016: Journal of Stroke
Jay Chol Choi, Ji Sung Lee, Tai Hwan Park, Yong-Jin Cho, Jong-Moo Park, Kyusik Kang, Kyung Bok Lee, Soo Joo Lee, Jae Guk Kim, Jun Lee, Man-Seok Park, Kang-Ho Choi, Joon-Tae Kim, Kyung-Ho Yu, Byung-Chul Lee, Mi-Sun Oh, Jae-Kwan Cha, Dae-Hyun Kim, Hyun-Wook Nah, Dong-Eog Kim, Wi-Sun Ryu, Beom Joon Kim, Hee-Joon Bae, Wook-Joo Kim, Dong-Ick Shin, Min-Ju Yeo, Sung Il Sohn, Jeong-Ho Hong, Juneyoung Lee, Keun-Sik Hong
BACKGROUND AND PURPOSE: About 30%-40% of stroke patients are taking antiplatelet at the time of their strokes, which might increase the risk of symptomatic intracranial hemorrhage (SICH) with intravenous tissue plasminogen activator (IV-TPA) therapy. We aimed to assess the effect of prestroke antiplatelet on the SICH risk and functional outcome in Koreans treated with IV-TPA. METHODS: From a prospective stroke registry, we identified patients treated with IV-TPA between October 2009 and November 2014...
September 2016: Journal of Stroke
Massoume Amini, Ali Deljou, Haidar Saify Nabiabad
Developmental deficiency of somatic embryos and regeneration to plantlets, especially in the case of transformation, are major problems of somatic embryo regeneration in alfalfa. One of the ways to overcome these problems is the use of natural plant regulators and nutrients in the culture medium of somatic embryos. For investigating the influence of Cuscuta campestris extract on the efficiency of plant regeneration and transformation, chimeric tissue type plasminogen activator was transferred to explants using Agrobacterium tumefaciens, and transgenic plants were recovered using medium supplemented with different concentration of the extract...
July 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
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