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https://www.readbyqxmd.com/read/28538012/antiphospholipid-syndrome-an-update-for-clinicians-and-scientists
#1
Andrew P Vreede, Paula L Bockenstedt, Jason S Knight
PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is unlikely to be made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28533669/prognostic-value-of-the-neutrophil-to-lymphocyte-ratio-for-hepatocellular-carcinoma-patients-with-portal-hepatic-vein-tumor-thrombosis
#2
Shao-Hua Li, Qiao-Xuan Wang, Zhong-Yuan Yang, Wu Jiang, Cong Li, Peng Sun, Wei Wei, Ming Shi, Rong-Ping Guo
AIM: To investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict the prognosis of hepatocellular carcinoma (HCC) patients with portal/hepatic vein tumor thrombosis (PVTT/HVTT) after hepatectomy. METHODS: The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: Overall survival (OS) and disease-free survival (DFS) were determined in the patients with a high (> 2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#3
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28504650/neutrophil-derived-s100-calcium-binding-proteins-a8-a9-promote-reticulated-thrombocytosis-and-atherogenesis-in-diabetes
#4
Michael J Kraakman, Man K S Lee, Annas Al-Sharea, Dragana Dragoljevic, Tessa J Barrett, Emilie Montenont, Debapriya Basu, Sarah Heywood, Helene L Kammoun, Michelle Flynn, Alexandra Whillas, Nordin M J Hanssen, Mark A Febbraio, Erik Westein, Edward A Fisher, Jaye Chin-Dusting, Mark E Cooper, Jeffrey S Berger, Ira J Goldberg, Prabhakara R Nagareddy, Andrew J Murphy
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28465447/human-blood-monocytes-are-able-to-form-extracellular-traps
#5
Vanessa Granger, Dorothée Faille, Vanessa Marani, Benoît Noël, Yann Gallais, Natacha Szely, Héloïse Flament, Marc Pallardy, Sylvie Chollet-Martin, Luc de Chaisemartin
Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase...
May 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28442532/anti-inflammatory-effects-of-simvastatin-during-the-resolution-phase-of-experimentally-formed-venous-thrombi
#6
Yaping Feng, Bo Lei, Fuxian Zhang, Luyuan Niu, Huan Zhang, Mingyi Zhang
Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days...
April 25, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28435267/the-acute-pulmonary-and-thrombotic-effects-of-cerium-oxide-nanoparticles-after-intratracheal-instillation-in-mice
#7
Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H Ali
Cerium oxide nanoparticles (CeO2 NPs), used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours) effect of intratracheal (IT) instillation of either CeO2 NPs (0.1 or 0.5 mg/kg) or saline (control) on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#8
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew P Cole, Marina Beltrami Moreira, Yiannis Chatzizisis, Thibaut Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin Croce, Peter Libby
Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis...
April 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#9
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#10
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28370080/evaluation-of-assays-for-quantification-of-dna-in-canine-plasma-as-an-indirect-marker-of-netosis
#11
Stephanie A Smith, Corinne M Lawson, Maureen A McMichael, Katrina Jung, Mauria O'Brien, Ron Achiel
BACKGROUND: Neutrophil extracellular traps (NET), consisting of a filamentous DNA/chromatin-histone scaffold originating from neutrophils are part of the innate immune response, may be released under a variety of inflammatory conditions and are associated with an increased risk for thrombosis. OBJECTIVES: The purpose of this study was to evaluate a SYTOX green fluorescence assay and a histone-DNA complex (hisDNA) ELISA for quantification of NET-related DNA in canine plasma...
April 3, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28359134/circulating-extracellular-dna-cause-or-consequence-of-thrombosis
#12
Miguel Jiménez-Alcázar, Natalie Kim, Tobias A Fuchs
Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism...
March 30, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28346125/canine-neutrophil-extracellular-traps-enhance-clot-formation-and-delay-lysis
#13
Unity Jeffery, Dana N LeVine
Autoimmune diseases increase the risk of thrombosis. Neutrophil extracellular traps (NETs) are webs of DNA and protein that may mediate thrombosis in autoimmune diseases. Human and murine studies show NET-releasing neutrophils within a thrombus promote its growth, but it is unclear to what extent NET fragments released into circulation during inflammation are prothrombotic. This study hypothesized that canine NETs promote clot formation and impair lysis even in the absence of neutrophils. NETs were prepared from PMA-stimulated neutrophils and added to fibrinogen and thrombin or to recalcified pooled canine platelet-poor plasma, tissue factor, and tissue plasminogen activator...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28331857/thrombosis-neuroinflammation-and-poststroke-infection-the-multifaceted-role-of-neutrophils-in-stroke
#14
REVIEW
Johanna Ruhnau, Juliane Schulze, Alexander Dressel, Antje Vogelgesang
Immune cells can significantly predict and affect the clinical outcome of stroke. In particular, the neutrophil-to-lymphocyte ratio was shown to predict hemorrhagic transformation and the clinical outcome of stroke; however, the immunological mechanisms underlying these effects are poorly understood. Neutrophils are the first cells to invade injured tissue following focal brain ischemia. In these conditions, their proinflammatory properties enhance tissue damage and may promote ischemic incidences by inducing thrombus formation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28329607/multiple-mucocutaneous-ulcers-associated-with-cocaine-induced-midline-destructive-lesions
#15
Brittany Blaise, Lucinda Buescher, Morgan L Wilson
Cocaine-induced midline destructive lesions (CIMDL) occur in a small subset of cocaine users, who clinically present with inflammation and necrosis of facial midline structures such as the palate, nasal septum, turbinates, and sinuses. We present a patient with CIMDL occurring concomitantly with ulcers on the cheek and upper trunk. Multiple biopsy specimens from the cutaneous and mucosal lesions consistently showed a dense dermal/submucosal infiltrate of neutrophils and plasma cells, without vasculitis or thrombosis...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28318536/chromobacterium-violaceum-infection-in-a-horse
#16
Márcia Elisa Hammerschmitt, Veronica Machado Rolim, Gustavo Geraldo Medina Snel, Franciele Maboni Siqueira, David Driemeier, Saulo Petinatti Pavarini
Chromobacterium violaceum is an opportunistic pathogen of mammals that produces characteristic violet pigment in bacterial culture. We report pneumonia and septicaemia caused by C. violaceum in a horse. Necropsy examination was performed on a 3-year-old Quarter Horse stallion with a history of recurrent episodes of pneumonia, fever, dyspnoea and sanguineous nasal discharge. The lungs were not collapsed, but they contained dark red foci mixed with white areas, and multiple nodules of firm consistency. Within the liver and kidney there were randomly distributed, multifocal, white pinpoint lesions (0...
March 16, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28303662/mean-platelets-volume-and-neutrophil-to-lymphocyte-ratio-as-predictors-of-stroke
#17
Raymond Farah, Nava Samra
BACKGROUND: Mean platelets volume (MPV) is a marker, which indicates platelet function, and is a potential link between inflammation and thrombosis. Previous studies have found a relation between high MPV levels and high risk of stroke. Another factor that has been associated with the risk of stroke is neutrophil to lymphocyte ratio (NLR). Several studies have reported an association between increased NLR and increased risk of cerebrovascular disease. It was found that NLR levels have a relation to the prognosis as well...
March 17, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28300869/e-selectin-inhibition-with-gmi-1271-decreases-venous-thrombosis-without-profoundly-affecting-tail-vein-bleeding-in-a-mouse-model
#18
Dorian L Culmer, Misha L Dunbar, Angela E Hawley, Suman Sood, Robert E Sigler, Peter K Henke, Thomas W Wakefield, John L Magnani, Daniel D Myers
Selectins, such as E-selectin (CD62E), function in venous thrombosis by binding and activating immune cells to initiate the coagulation cascade. GMI-1271 is a small molecule antagonist that inhibits E-selectin activity. Here we determine whether inhibition of E-selectin is sufficient to decrease acute venous thrombosis and associated inflammatory events in both prophylactic and treatment protocols without significantly affecting haemostasis. Male C57BL/6 mice underwent surgery for experimental thrombosis induction and were harvested at peak thrombus formation in our animal model, two days post induction...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28270931/design-and-methods-of-the-pan-canadian-applying-biomarkers-to-minimize-long-term-effects-of-childhood-adolescent-cancer-treatment-able-nephrotoxicity-study-a-prospective-observational-cohort-study
#19
Kelly R McMahon, Shahrad Rod Rassekh, Kirk R Schultz, Maury Pinsk, Tom Blydt-Hansen, Cherry Mammen, Ross T Tsuyuki, Prasad Devarajan, Geoff D E Cuvelier, Lesley G Mitchell, Sylvain Baruchel, Ana Palijan, Bruce C Carleton, Colin J D Ross, Michael Zappitelli
BACKGROUND: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28245630/structural-basis-of-native-cxcl7-monomer-binding-to-cxcr2-receptor-n-domain-and-glycosaminoglycan-heparin
#20
Aaron J Brown, Krishna Mohan Sepuru, Krishna Rajarathnam
CXCL7, a chemokine highly expressed in platelets, orchestrates neutrophil recruitment during thrombosis and related pathophysiological processes by interacting with CXCR2 receptor and sulfated glycosaminoglycans (GAG). CXCL7 exists as monomers and dimers, and dimerization (~50 μM) and CXCR2 binding (~10 nM) constants indicate that CXCL7 is a potent agonist as a monomer. Currently, nothing is known regarding the structural basis by which receptor and GAG interactions mediate CXCL7 function. Using solution nuclear magnetic resonance (NMR) spectroscopy, we characterized the binding of CXCL7 monomer to the CXCR2 N-terminal domain (CXCR2Nd) that constitutes a critical docking site and to GAG heparin...
February 26, 2017: International Journal of Molecular Sciences
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