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Tissue plasminogen activator

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https://www.readbyqxmd.com/read/28328682/early-tranexamic-acid-administration-ameliorates-the-endotheliopathy-of-trauma-and-shock-in-an-in-vitro-model
#1
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma-hemorrhagic shock (T/HS) which results in disturbances of coagulation, inflammation and endothelial barrier integrity. The effect of T/HS on the endothelium (Endotheliopathy of Trauma)[EoT] is of intense research interest and may lead to EoT directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury. Mechanisms for this protective effect include the anti-fibrinolytic and anti-inflammatory effects of TXA...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28324671/dose-de-escalation-of-intrapleural-tissue-plasminogen-activator-therapy-for-pleural-infection-the-adapt-project
#2
Natalia Popowicz, Oliver Bintcliffe, Duneesha De Fonseka, Kevin G Blyth, Nicola A Smith, Francesco Piccolo, Geoffrey Martin, Donny Wong, Anthony Edey, Nick Maskell, Y C Gary Lee
RATIONALE: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10mg and deoxyribonuclease (DNase) 5mg administered twice daily has been shown in randomized and open-label studies to enable adequate drainage of over 90% of infected pleural effusions without surgery. Potential bleeding risks associated with intrapleural tPA and the drug costs remain important concerns. The ongoing ADAPT (Alteplase Dose Assessment for Pleural infection Therapy) project aims to investigate the efficacy and safety of dose de-escalation for intrapleural tPA...
March 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28322975/a-polymeric-micelle-magnetic-resonance-imaging-mri-contrast-agent-reveals-blood-brain-barrier-bbb-permeability-for-macromolecules-in-cerebral-ischemia-reperfusion-injury
#3
Kouichi Shiraishi, Zuojun Wang, Daisuke Kokuryo, Ichio Aoki, Masayuki Yokoyama
Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments...
March 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28322071/an-additional-bolus-of-rapid-acting-insulin-to-normalise-postprandial-cardiovascular-risk-factors-following-a-high-carbohydrate-high-fat-meal-in-patients-with-type-1-diabetes-a-randomised-controlled-trial
#4
Matthew D Campbell, Mark Walker, Ramzi A Ajjan, Karen M Birch, Javier T Gonzalez, Daniel J West
AIM: To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. METHODS: A total of 10 males with type 1 diabetes [HbA1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA)...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28320709/plasmin-and-plasminogen-induce-macrophage-reprogramming-and-regulate-key-steps-of-inflammation-resolution-via-annexin-a1
#5
Michelle A Sugimoto, Ana Luíza C Ribeiro, Bruno R C Costa, Juliana P Vago, Kátia M Lima, Fernanda S Carneiro, Mylena Maira O Ortiz, Graziele Letícia N Lima, Aline A F Carmo, Renata M Rocha, Denise A Perez, Alessandra C Reis, Vanessa Pinho, Lindsey A Miles, Cristiana C Garcia, Mauro M Teixeira, Lirlândia P Sousa
Inflammation resolution is an active process that functions to restore tissue homeostasis. Participation of the plasminogen/plasmin (Plg/Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 - F4/80(high) Gr1(-) CD11b(high)) and proresolving (Mres - F4/80(med) CD11b(low)) phenotypes, without changing the number of macrophages with a pro-inflammatory profile (M1 - F4/80(low) Gr1(+) CD11b(med))...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28319824/effect-of-long-term-remote-ischaemic-conditioning-on-platelet-function-and-fibrinolysis-in-patients-with-chronic-ischaemic-heart-failure
#6
Kasper Pryds, Jacobina Kristiansen, Søs Neergaard-Petersen, Roni R Nielsen, Michael R Schmidt, Jens Refsgaard, Steen D Kristensen, Hans Erik Bøtker, Anne-Mette Hvas, Erik L Grove
INTRODUCTION: Remote ischaemic conditioning (RIC) protects against ischaemia-reperfusion injury through cellular protective pathways, but may also modulate haemostasis. We aimed to investigate the effect of long-term RIC on platelet function and fibrinolysis in patients with chronic ischaemic heart failure (CIHF). MATERIAL AND METHODS: In a prospective, outcome-assessor blinded, paired study, 16 patients with CIHF and 21 age- and gender-matched controls without ischaemic heart disease (IHD) were treated with RIC once daily for 28±4days...
March 10, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28319440/markers-of-blood-coagulation-and-fibrinolysis-in-patients-with-early-and-delayed-microsurgical-reconstructions-in-the-lower-extremities
#7
Oliver Kloeters, Dalibor Vasilic, Pieter Hupkens, Dietmar Ulrich
BACKGROUND: In this study, markers of coagulation and fibrinolysis were assessed during early and delayed microsurgical reconstruction in patients with traumatic defects of their lower legs to analyse whether an imbalance of the hemostasis after trauma might predispose the development of vascular complications. METHODS: The prospective study included 70 patients. In 35 patients, surgery was performed within 72 hours after injury. In 35 other patients, delayed free flap transfer was performed between 14-21 days after trauma...
March 20, 2017: Journal of Plastic Surgery and Hand Surgery
https://www.readbyqxmd.com/read/28306132/evaluation-of-functional-outcome-measured-by-modified-rankin-scale-in-rtpa-treated-patients-with-acute-ischemic-stroke
#8
B Georgievski-Brkic, M Savic, D Nikolic, L Nikcevic, M Vukicevic, D Kozic
Aim of our study was to assess functional outcome measured by modified Rankin scale (mRS) in patients that were treated with thrombolytic therapy-recombinant tissue plasminogen activator (rtPA) after acute ischemic stroke. The study included 100 participants that were treated after acute ischemic stroke. Analyzed parameters included: gender; age groups: age 54 and below (Groupup to-54), 55-64 (Group55-64), 65-74 (Group65-74), and 75 and above (Group75-up); cerebral blood flow (CBF) and cerebral blood volume (CBV)...
December 1, 2016: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28304205/stenting-of-the-cervical-internal-carotid-artery-in-acute-stroke-management-the-karolinska-experience
#9
Anastasios Mpotsaris, Christoph Kabbasch, Jan Borggrefe, Vamsi Gontu, Michael Soderman
Background Emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy is a routine procedure. Yet, precise indications and clinical safety in this setting remains controversial. Present data for mechanical thrombectomy include few studies with acute stenting of tandem occlusions. We evaluated the feasibility, safety and clinical outcome of this endovascular treatment in a retrospective analysis of all consecutive cases at a comprehensive stroke centre...
April 2017: Interventional Neuroradiology
https://www.readbyqxmd.com/read/28303501/isoflurane-postconditioning-inhibits-tpa-induced-matrix-metalloproteinases-activation-after-hypoxic-injury-via-low-density-lipoprotein-receptor-related-protein-and-extracellular-signal-regulated-kinase-pathway
#10
So Yeon Kim, So Yeong Cheon, Eun Jung Kim, Jae Hoon Lee, Eun Hee Kam, Jeong Min Kim, Miran Park, Bon-Nyeo Koo
Tissue plasminogen activator (tPA) is the only recommended pharmacological treatment for acute ischemic stroke. However, tPA can induce intracerebral hemorrhage by blood-brain barrier breakdown through an increase in matrix metalloproteinases (MMPs). Previously, we showed that isoflurane postconditioning reduced intracranial hemorrhage following tPA treatment after cerebral ischemia. Here, we investigated the mechanism by which isoflurane postconditioning reduces tPA-induced MMP-2 and MMP-9 activation following hypoxia/reoxygenation (H/R) in brain endothelial cells...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28303356/the-association-of-plasminogen-activator-inhibitor-type-1-pai-1-level-and-pai-1-4g-5g-gene-polymorphism-with-the-formation-and-the-grade-of-endometrial-cancer
#11
Malik Ejder Yıldırım, Savas Karakuş, Hande Küçük Kurtulgan, Hasan Kılıçgün, Serpil Erşan, Sevtap Bakır
Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism...
March 16, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28302915/sex-differences-in-ischaemic-stroke-potential-cellular-mechanisms
#12
REVIEW
Anjali Chauhan, Hope Moser, Louise D McCullough
Stroke remains a leading cause of mortality and disability worldwide. More women than men have strokes each year, in part because women live longer. Women have poorer functional outcomes, are more likely to need nursing home care and have higher rates of recurrent stroke compared with men. Despite continued advancements in primary prevention, innovative acute therapies and ongoing developments in neurorehabilitation, stroke incidence and mortality continue to increase due to the aging of the U.S. POPULATION: Sex chromosomes (XX compared with XY), sex hormones (oestrogen and androgen), epigenetic regulation and environmental factors all contribute to sex differences...
April 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28301587/the-duplication-mutation-of-quebec-platelet-disorder-dysregulates-plau-but-not-c10orf55-selectively-increasing-production-of-normal-plau-transcripts-by-megakaryocytes-but-not-granulocytes
#13
Catherine P M Hayward, Minggao Liang, Subia Tasneem, Asim Soomro, John S Waye, Andrew D Paterson, Georges E Rivard, Michael D Wilson
Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 78 kb region of chromosome 10 containing PLAU (the uPA gene) and C10orf55, a gene of unknown function. QPD increases uPA in platelets and megakaryocytes >100 fold, far more than expected for a gene duplication. To investigate the tissue-specific effect that PLAU duplication has on gene expression and transcript structure in QPD, we tested if QPD leads to: 1) overexpression of normal or unique PLAU transcripts; 2) increased uPA in leukocytes; 3) altered levels of C10orf55 mRNA and/or protein in megakaryocytes and leukocytes; and 4) global changes in megakaryocyte gene expression...
2017: PloS One
https://www.readbyqxmd.com/read/28298840/the-need-for-a-population-based-dose-optimization-study-for-recombinant-tissue-plasminogen-activator-in-acute-ischemic-stroke-a-study-from-a-tertiary-care-teaching-hospital-from-south-india
#14
Siju V Abraham, Fazil Thaha, S Vimal Krishnan, Athulya Shajan, Jayaraj Mymbilly Balakrishnan, Babu Urumese Palatty
CONTEXT: The guideline recommended dose of intravenous (i.v) recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke is 0.9 mg/kg in the European and American populations. In Asiatic population, some studies have shown that a lower dose of i.v rt-PA is equally efficacious. AIMS: To assess if there is a need for a dose optimization for i.v rt-PA study among Indians. SETTING AND DESIGN: A prospective, observational database of acute stroke cases that presented to a tertiary care institute over a period of 1 year was made...
January 2017: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/28298456/microglial-complement-receptor-3-regulates-brain-a%C3%AE-levels-through-secreted-proteolytic-activity
#15
Eva Czirr, Nicholas A Castello, Kira I Mosher, Joseph M Castellano, Izumi V Hinkson, Kurt M Lucin, Bernat Baeza-Raja, Jae Kyu Ryu, Lulin Li, Sasha N Farina, Nadia P Belichenko, Frank M Longo, Katerina Akassoglou, Markus Britschgi, John R Cirrito, Tony Wyss-Coray
Recent genetic evidence supports a link between microglia and the complement system in Alzheimer's disease (AD). In this study, we uncovered a novel role for the microglial complement receptor 3 (CR3) in the regulation of soluble β-amyloid (Aβ) clearance independent of phagocytosis. Unexpectedly, ablation of CR3 in human amyloid precursor protein-transgenic mice results in decreased, rather than increased, Aβ accumulation. In line with these findings, cultured microglia lacking CR3 are more efficient than wild-type cells at degrading extracellular Aβ by secreting enzymatic factors, including tissue plasminogen activator...
March 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28298247/tissue-specific-inhibition-of-urokinase-type-plasminogen-activator-expression-in-the-testes-of-mice-by-inducible-lentiviral-rna-interference-causes-male-infertility
#16
Kai Zhao, Yan Liu, Zhe Xiong, Lian Hu, Cheng-Liang Xiong
Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1μgmL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6/TR) were co-microinjected into mouse testes to produce TetR&shuPA mice model. Though oral gavage by 0...
March 16, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28298139/emergent-carotid-stenting-and-intra-arterial-abciximab-in-acute-ischemic-stroke-due-to-tandem-occlusion
#17
Fawaz Al-Mufti, Krishna Amuluru, Nathan W Manning, Imad Khan, Lissa Peeling, Chirag D Gandhi, Charles J Prestigiacomo, Galyna Pushchinska, David Fiorella, Henry H Woo
OBJECTIVE: Acute occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. The aim of our study was to retrospectively delineate the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) Abciximab with intracranial revascularization in the setting of acute ischemic stroke and carotid occlusions at our institution. METHODS: Eleven patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit...
March 15, 2017: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/28297015/mortality-following-cardiovascular-and-bleeding-events-occurring-beyond-1-year-after-coronary-stenting-a-secondary-analysis-of-the-dual-antiplatelet-therapy-dapt-study
#18
Eric A Secemsky, Robert W Yeh, Dean J Kereiakes, Donald E Cutlip, David J Cohen, P Gabriel Steg, Christopher P Cannon, Patricia K Apruzzese, Ralph B D'Agostino, Joseph M Massaro, Laura Mauri
Importance: Early cardiovascular and bleeding events after coronary stenting are associated with high risk of morbidity and mortality. Objective: To assess the prognosis of cardiovascular and bleeding events occurring beyond 1 year after coronary stenting. Design, Setting, and Participants: This secondary analysis is derived from data from the Dual Antiplatelet Therapy (DAPT) Study, a multicenter trial involving 220 US and international clinical sites from 11 countries...
March 15, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28296671/the-use-of-thrombolytic-therapy-in-the-treatment-of-frostbite-injury
#19
Allyson Wexler, Sarah Zavala
Frostbite can lead to severe consequences including loss of digits and limbs. One of the mechanisms of frostbite includes vascular thrombosis. The use of tissue plasminogen activator (tPA) in frostbite has been shown to be effective in case reports and small prospective studies. A retrospective chart review was performed on all patients admitted for frostbite between January 2008 and April 2015, and six patients were identified as having received treatment with intravenous tPA. Patients received an initial bolus dose followed by a 6-hour infusion of tPA...
March 3, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28295306/osteoactivin-regulates-head-and-neck-squamous-cell-carcinoma-invasion-by-modulating-matrix-metalloproteases
#20
Oneida A Arosarena, Eric W Barr, Ryan Thorpe, Hilary Yankey, Joseph T Tarr, Fayez F Safadi
Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. OBJECTIVES: To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion...
March 10, 2017: Journal of Cellular Physiology
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