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Tissue plasminogen activator

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https://www.readbyqxmd.com/read/28230174/a-hydrophobic-patch-surrounding-trp154-in-human-neuroserpin-controls-the-helix-f-dynamics-with-implications-in-inhibition-and-aggregation
#1
Mohammad Farhan Ali, Abhinav Kaushik, Charu Kapil, Dinesh Gupta, Mohamad Aman Jairajpuri
Neuroserpin (NS) mediated inhibition of tissue-type plasminogen activator (tPA) is important for brain development, synapse formation and memory. Aberrations in helix F and β-sheet A movement during inhibition can directly lead to epilepsy or dementia. Conserved W154 residue in a hydrophobic patch between helix F and β-sheet A is ideally placed to control their movement during inhibition. Molecular Dynamics (MD) simulation on wild type (WT) NS and its two variants (W154A and W154P) demonstrated partial deformation in helix F and conformational differences in strands 1A and 2A only in W154P...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228574/delays-in-door-to-needle-times-and-their-impact-on-treatment-time-and-outcomes-in-get-with-the-guidelines-stroke
#2
Noreen Kamal, Shubin Sheng, Ying Xian, Roland Matsouaka, Michael D Hill, Deepak L Bhatt, Jeffrey L Saver, Mathew J Reeves, Gregg C Fonarow, Lee H Schwamm, Eric E Smith
BACKGROUND AND PURPOSE: Despite quality improvement programs such as the American Heart Association/American Stroke Association Target Stroke initiative, a substantial portion of acute ischemic stroke patients are still treated with tissue-type plasminogen activator (alteplase) later than 60 minutes from arrival. This study aims to describe the documented reasons for delays and the associations between reasons for delays and patient outcomes. METHODS: We analyzed the characteristics of 55 296 patients who received intravenous alteplase in 1422 hospitals participating in Get With The Guidelines-Stroke from October 2012 to April 2015, excluding transferred patients and inpatient strokes...
February 22, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28228323/evaluation-of-the-role-of-susceptibility-weighted-imaging-in-thrombolytic-therapy-for-acute-ischemic-stroke
#3
Guangjian Zhao, Ling Sun, Ziran Wang, Liquan Wang, Zhongrong Cheng, Hongyan Lei, Daiqun Yang, Yansen Cui, Shirui Zhang
We inspected low-intensity venous signals and microbleeds in patients with acute ischemic stroke (AIS) using susceptibility-weighted imaging (SWI) before and after administration of within-thrombolytic-time-window thrombolytic therapies, and observed their prognosis and safety, in order to guide individualized thrombolytic therapies. Patients with AIS were divided into groups A or B according to the presence of symmetric or asymmetric veins on SWI, and were re-inspected by SWI after intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA)...
February 19, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28227899/peripheral-sensory-stimulation-is-neuroprotective-in-a-rat-photothrombotic-ischemic-stroke-model
#4
Aishwarya Bandla, Chua Le Teng Sherry, Frances Lim, Chan Kim Chuan, Lun-De Liao, Nitish V Thakor, Aishwarya Bandla, Chua Le Teng Sherry, Frances Lim, Chan Kim Chuan, Lun-De Liao, Nitish V Thakor, Lun-De Liao, Nitish V Thakor, Frances Lim, Chua Le Teng Sherry, Aishwarya Bandla, Chan Kim Chuan
Ischemic stroke is one of the leading causes of death and disability in the world. Thrombolytic therapy using recombinant tissue plasminogen activator (rtPA), the only FDA-approved drug for acute ischemia, is limited by a narrow therapeutic time window and risk of hemorrhage. There is a serious need for a neuroprotective therapy which is clinically viable. We earlier demonstrated that peripheral sensory stimulation (PSS) is a potential therapeutic intervention for hyperacute ischemia resulting in recovery of neurovascular functions when administered immediately following ischemia onset in a rat model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227393/an-integrated-neuroprotective-intervention-for-brain-ischemia-validated-by-ecog-fpam
#5
Yu-Hang Liu, Lun-De Liao, Su Jing Chan, Aishwarya Bandla, Nitish V Thakor, Yu-Hang Liu, Lun-De Liao, Su Jing Chan, Aishwarya Bandla, Nitish V Thakor, Yu-Hang Liu, Aishwarya Bandla, Nitish V Thakor, Su Jing Chan, Lun De Liao
Brain ischemia is a neurological deficit caused by a reduction in the blood supply to tissue, and one of the leading causes of disability in the world. Currently, the most well-known therapeutic agent for ischemia recovery is recombinant tissue plasminogen activator (rtPA), but it is viable for only a small portion (approximately 3.6%) of ischemic patients and may cause side effects such as tissue damage. Thus, introducing a new therapeutic concept for ischemia, we proposed an integrated intervention combining global and focal stimulations in this article...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223717/scale-up-and-pharmacokinetic-study-of-a-novel-mutated-chimeric-tissue-plasminogen-activator-mt-pa-in-rats
#6
Mozhgan Raigani, Mohammad-Reza Rouini, Ali-Akbar Golabchifar, Esmat Mirabzadeh, Behrouz Vaziri, Farzaneh Barkhordari, Fatemeh Davami, Fereidoun Mahboudi
Because of high mortality caused by cardiovascular diseases, various fibrinolytic agents with diverse pharmacokinetic and pharmacodynamic properties have been developed. A novel mutated chimeric tissue plasminogen activator (mt-PA) was developed by the removal of first three domains of t-PA, insertion of GHRP sequence and mutation towards resistance to plasminogen activator inhibitor-1 (PAI-1). Mt-PA protein was expressed in Expi293F cells. The expression level of mt-PA was found to be 5000 IU/mL. Following purification, the pharmacokinetic properties of mt-PA were evaluated in three doses in rats...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222621/digestive-and-urologic-hemorrhage-after-intravenous-thrombolysis-for-acute-ischemic-stroke-data-from-a-chinese-stroke-center
#7
Hong Chang, Xiaojuan Wang, Xin Yang, Haiqing Song, Yuchen Qiao, Jia Liu
Objective Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is considered the most effective treatment method for AIS; however, it is associated with a risk of hemorrhage. We analyzed the risk factors for digestive and urologic hemorrhage during rt-PA therapy. Methods We retrospectively analyzed patients with AIS who underwent intravenous thrombolysis with rt-PA during a 5-year period in a Chinese stroke center. Data on the demographics, medical history, laboratory test results, and clinical outcomes were collected...
February 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28222238/thrombolysis-with-intravenous-recombinant-tissue-plasminogen-activator-during-early-postpartum-period-a-review-of-the-literature
#8
Munetoshi Akazawa, Makoto Nishida
Thromboembolic events are one of the leading causes of maternal death during the postpartum period. Postpartum thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is controversial because the treatment may lead to massive bleeding. Data centralization may be beneficial for analyzing the safety and effectiveness of systemic thrombolysis during the early postpartum period. We performed a computerized MEDLINE and EMBASE search. We collected data for 13 cases of systemic thrombolytic therapy during the early postpartum period, when limiting the early postpartum period to 48 hours after delivery...
February 21, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28222056/physical-activity-sedentary-behavior-and-inflammatory-and-hemostatic-markers-in-men
#9
Tessa J Parsons, Claudio Sartini, Paul Welsh, Naveed Sattar, Sarah Ash, Lucy T Lennon, S Goya Wannamethee, I-Min Lee, Peter H Whincup, Barbara J Jefferis
PURPOSE: This study aimed to determine whether higher levels of physical activity (PA) and less sedentary behavior (SB) are associated with less inflammation, indicated by inflammatory and hemostatic biomarkers, in older men. METHODS: A cross-sectional study of 1139 men, from the British Regional Heart Study (mean ± SD age = 78 ± 5 yr), and longitudinal analyses of 490 men with two PA measures 1 yr apart were used in this study. Single fasting venous blood samples were analyzed for several biomarkers...
March 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28219452/stop-stroke-a-brief-report-on-door-to-needle-times-and-performance-after-implementing-an-acute-care-coordination-medical-application-and-implications-to-emergency-medical-services
#10
Robert Dickson, Adrian Nedelcut, Melissa McPeek Nedelcut
OBJECTIVE: The objective of this study was to evaluate the effect of the Stop Stroke (Pulsara; Bozeman, Montana USA) medical application on door-to-needle (DTN) time in patients presenting to the emergency department (ED) with an acute ischemic stroke (AIS). METHODS: This was a retrospective cohort study of the Good Shepherd Health System (Longview, Texas USA) stroke quality improvement dashboard for a 25-month period from February 2012 through February 2014. Data analysis includes all data from Center for Medicare and Medicaid Services (CMS; Baltimore, Maryland USA) reportable cases receiving Tissue Plasminogen Activator (TPA) for AIS during the study period...
February 21, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28217292/oxygen-or-cooling-to-make-a-decision-after-acute-ischemia-stroke
#11
REVIEW
Wen-Cao Liu, Xin-Chun Jin
The presence of a salvageable penumbra, a region of ischemic brain tissue with sufficient energy for short-term survival, has been widely agreed as the premise for thrombolytic therapy with tissue plasminogen activator (tPA), which remains the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic transformation (HT)...
October 2016: Medical Gas Research
https://www.readbyqxmd.com/read/28214482/catheter-directed-ultrasound-assisted-thrombolysis-is-a-safe-and-effective-treatment-for-pulmonary-embolism-even-in-high-risk-patients
#12
Kristen A Lee, Andrew Cha, Mark H Kumar, Combiz Rezayat, Clifford M Sales
OBJECTIVE: We sought to assess the early success and safety of catheter-directed, ultrasound-assisted (CDUA) thrombolysis for acute pulmonary embolism (PE) in patients deemed to be "high risk" for thrombolytic therapy. METHODS: A retrospective evaluation of patients who underwent CDUA pulmonary thrombolysis in our practice during 39 months is reported. There were 91 patients considered, all of whom presented with acute PE as diagnosed by computed tomography angiography...
March 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28211169/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects
#13
Jin Zhou, Jarema Kochan, Ophelia Yin, Vance Warren, Cynthia Zamora, George Atiee, Joseph Pav, Yasushi Orihashi, Vijay Vashi, Victor Dishy
BACKGROUND: Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low-molecular weight compound inhibiting the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), developed as a fibrinolysis enhancer for treatment of thromboembolic diseases. OBJECTIVES: This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040 in healthy subjects...
February 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28210988/real-life-experience-with-the-specific-reversal-agent-idarucizumab-for-the-management-of-emergency-situations-in-dabigatran-treated-patients-a-series-of-11-cases
#14
Milan R Vosko, Christof Bocksrucker, Rafał Drwiła, Petr Dulíček, Tomas Hauer, Johannes Mutzenbach, Christoph J Schlimp, David Špinler, Thomas Wolf, Daša Zugwitz
Non-vitamin K antagonist oral anticoagulants (NOACs) have a favorable benefit-risk profile compared with vitamin K antagonists. However, the lack of specific reversal agents has made the management of some patients receiving long-term treatment with NOACs problematic in emergency situations such as major bleeding events or urgent procedures. Idarucizumab, a fully humanized Fab antibody fragment that binds specifically and with high affinity to dabigatran, was recently approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effect is required...
February 16, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28210916/a-multiscale-mathematical-model-of-tumour-invasive-growth
#15
Lu Peng, Dumitru Trucu, Ping Lin, Alastair Thompson, Mark A J Chaplain
Known as one of the hallmarks of cancer (Hanahan and Weinberg in Cell 100:57-70, 2000) cancer cell invasion of human body tissue is a complicated spatio-temporal multiscale process which enables a localised solid tumour to transform into a systemic, metastatic and fatal disease. This process explores and takes advantage of the reciprocal relation that solid tumours establish with the extracellular matrix (ECM) components and other multiple distinct cell types from the surrounding microenvironment. Through the secretion of various proteolytic enzymes such as matrix metalloproteinases or the urokinase plasminogen activator (uPA), the cancer cell population alters the configuration of the surrounding ECM composition and overcomes the physical barriers to ultimately achieve local cancer spread into the surrounding tissue...
February 16, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28209486/vasodilator-stimulated-phosphoprotein-vasp-depletion-from-breast-cancer-mda-mb-231-cells-inhibits-tumor-spheroid-invasion-through-downregulation-of-migfilin-%C3%AE-catenin-and-urokinase-plasminogen-activator-upa
#16
Vasiliki Gkretsi, Andreas Stylianou, Triantafyllos Stylianopoulos
A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP...
February 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28207534/a-case-control-study-on-the-structural-equation-model-of-the-mechanism-of-coagulation-and-fibrinolysis-imbalance-in-chronic-schistosomiasis
#17
Aiping Le, Lunli Zhang, Wei Liu, Xiaopeng Li, Jianwei Ren, An Ning
A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28206731/thrombus-resolution-and-right-ventricular-functional-recovery-using-ultrasound-accelerated-thrombolysis-in-acute-massive-and-submassive-pulmonary-embolism
#18
Evren Ozcinar, Mehmet Cakici, Nur Dikmen Yaman, Cagdas Baran, Anar Aliyev, Bahadir Inan, Serkan Durdu, Ahmet R Akar, Mustafa Sirlak
BACKGROUND: This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter- directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). METHODS: We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64...
February 15, 2017: International Angiology: a Journal of the International Union of Angiology
https://www.readbyqxmd.com/read/28202868/rt-pa-with-antithrombotic-therapies-in-a-case-with-capsular-warning-syndrome
#19
Yasuhiro Fuseya, Miyuki Kawamura, Eri Matsuda, Kozue Takada, Kiwamu Watanabe, Junko Fujitake, Yoshifumi Nakaya
We herein report a case of capsular warning syndrome (CWS) that was successfully treated with recombinant tissue plasminogen activator (rt-PA). A 70-year-old woman had repeated stereotyped transient ischemic attacks (TIAs) of right hemiparesis and dysarthria. After hospitalization, argatroban, aspirin, and cilostazol were started but were ineffective. Thirteen hours after the first episode of TIAs, severe symptoms occurred. Magnetic resonance imaging showed acute infarctions in the internal capsule to corona radiata, so we used rt-PA...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28202820/-clinical-manifestations-of-spinal-epidural-hematoma-stroke-mimic-and-pitfalls-in-diagnosis
#20
Masaru Kuriyama
Clinical manifestations of spinal epidural hematoma are presented, and the cases mimicking acute ischemic stroke have been reviewed from the literature. Many reports described the cases of spinal epidural hematoma with acute hemiparesis mimicking ischemic stroke in which intravenous thrombolytic treatment with recombinant tissue plasminogen activator was considered. A correct diagnosis of acute ischemic stroke must be made within 4.5 hours from the onset of symptoms, a relatively short window period. A spinal epidural hematoma is a potentially important stroke mimic in a wide variety of conditions that mimic a stroke...
February 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
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