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https://www.readbyqxmd.com/read/29757405/platelets-drive-inflammation-and-target-gray-matter-and-the-retina-in-autoimmune-mediated-encephalomyelitis
#1
Claretta Sonia D'Souza, Zenjiang Li, Dain Luke Maxwell, Oliver Trusler, Melanie Murphy, Sheila Crewther, Karlheinz Peter, Jacqueline Monique Orian
Despite growing evidence for platelets as active players in infection and immunity, it remains unresolved whether platelets contribute to, or are key elements in the development of neuroinflammation. Using the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we identified platelet accumulation in the circulation by 7-day postinduction (dpi), ahead of clinical onset which occurs at 13-14 dpi. By inducing platelet depletion between 7 and 16 dpi, we demonstrate an association between platelet accumulation in the spinal cord and disease development...
May 10, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29756276/a-novel-diagnostic-algorithm-for-heparin-induced-thrombocytopenia
#2
G Zheng, M B Streiff, D Allison, C M Takemoto, K Salimian, P Morris, J Jani, R McCord, T S Kickler
INTRODUCTION: While diagnostic algorithm using PF4-heparin enzyme-linked immunosorbent assay (ELISA) optical density (OD), and heparin neutralization assay (HNA), or 4T score have been proposed to replace serotonin-release assay (SRA) for heparin-induced thrombocytopenia (HIT), their performance against SRA is unclear. In this study, we proposed and validated the performance of a new algorithm combining PF4-heparin ELISA optical density (OD), HNA and 4T score against SRA for HIT diagnosis...
May 13, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29754444/peptidome-analysis-reveals-novel-serum-biomarkers-for-children-with-autism-spectrum-disorder-in-china
#3
Juan Yang, Yanni Chen, Xiaofan Xiong, Xiaobo Zhou, Lin Han, Ei Ni, Wenjing Wang, Xiaofei Wang, Lingyu Zhao, Dongdong Shao, Chen Huang
PURPOSE: Autism spectrum disorder (ASD) is a neurological and developmental disorder that begins early in childhood and lasts throughout one's life. Early diagnosis is essential for ASD since early treatment can enable children with ASD to make significant gains in language and social skills, but remains challenging since there are currently no specific biomarkers of ASD. The study aimed to identify serum biomarkers for ASD. EXPERIMENTAL DESIGN: Serum of Han Chinese children with ASD (n = 68) and age-matched healthy controls (n = 80) was analyzed using magnetic bead-based separation combined with mass spectrum...
May 13, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29723924/cellular-immune-responses-to-platelet-factor-4-and-heparin-complexes-in-patients-with-heparin-induced-thrombocytopenia
#4
Ishac Nazy, Rumi Clare, Phillip Staibano, Theodore E Warkentin, Mark Larche, Jane C Moore, James W Smith, Richard P Whitlock, John G Kelton, Donald M Arnold
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin characterized by thrombocytopenia and thrombotic complications. HIT is caused by pathogenic antibodies that bind to complexes of platelet factor 4 and heparin (PF4/heparin) leading to platelet activation and inducing a hypercoagulable state. Previous studies have shown immunity to PF4/heparin occurs early in life even before heparin exposure; however, the immunogenesis of HIT is not well characterized...
May 3, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29713904/gene-expression-changes-in-the-retina-after-systemic-administration-of-aldosterone
#5
Aoi Ono, Kazuyuki Hirooka, Yuki Nakano, Eri Nitta, Akira Nishiyama, Akitaka Tsujikawa
PURPOSE: Retinal ganglion cell (RGC) loss associated with thinning of the retinal nerve fiber layer without elevated intraocular pressure (IOP) occurs after the systemic administration of aldosterone. Since it is important to determine the mechanism of cell death independent of the IOP, we examined gene expression changes in the retina after the systemic administration of aldosterone. METHODS: Following subcutaneous implantation of an osmotic minipump into the mid-scapular region of rats, we administered an 80 μg/kg/day dose of aldosterone...
April 30, 2018: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29698332/serum-proteomics-in-african-american-female-patients-with-irritable-bowel-syndrome-an-exploratory-study
#6
Kristen R Weaver, Gail D' Eramo Melkus, Jason Fletcher, Wendy A Henderson
BACKGROUND: Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. OBJECTIVES: The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology...
May 2018: Nursing Research
https://www.readbyqxmd.com/read/29678479/hit-or-miss-a-comprehensive-contemporary-investigation-of-laboratory-tests-for-heparin-induced-thrombocytopenia
#7
Emmanuel J Favaloro, Georgia McCaughan, Soma Mohammed, Kun Kan Edwin Lau, Rosalie Gemmell, Lauren Cavanaugh, Dea Donikian, Mayuko Kondo, Timothy Brighton, Leonardo Pasalic
Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG(PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]...
April 17, 2018: Pathology
https://www.readbyqxmd.com/read/29661682/absolute-immature-platelet-counts-in-the-setting-of-suspected-heparin-induced-thrombocytopenia-may-predict-anti-pf4-heparin-immunoassay-testing-results
#8
Wei Chen, Jennifer P Ha, Hong Hong, Robert W Maitta
BACKGROUND: Heparin-induced-thrombocytopenia (HIT) is a disease mediated by antibodies to platelet factor 4 (PF4)-heparin complexes. Immature platelet fraction (%-IPF) and absolute immature platelet count (A-IPC) measure newly-released platelets into circulation and can prove useful in differentiating patients with thrombocytopenic presentations due to consumptive or hypoproduction processes. Therefore, we evaluated utility of A-IPC in a cohort of thrombocytopenic patients suspected of HIT...
April 11, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29628468/induction-of-anti-pf4-heparin-antibodies-after-arthroplasty-for-rheumatic-diseases
#9
Kiyoshi Migita, Tomoyuki Asano, Shuzo Sato, Satoru Motokawa
Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. These pathogenic antibodies against PF4/heparin bind and activate cellular FcγRIIa on platelets to induce a hypercoagulable state culminating in thrombosis. Recent studies indicate several conditions, including joint surgery, induce spontaneous HIT, which can occur without exposure to heparin. To determine the real-world evidences concerning the incidences of venous thromboembolism (VTE) after total joint arthroplasty for rheumatic disease, we conducted a multicenter cohort study (J-PSVT) designed to document the VTE and seroconversion rates of anti-PF4/heparin antibody in 34 Japanese National hospital organization (NHO) hospitals...
April 7, 2018: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/29617417/role-of-protein-kinase-c-delta-in-regulating-platelet-activation-and-platelet-leukocyte-interaction-during-sepsis
#10
Elisabetta Liverani, Mark J Mondrinos, Shuang Sun, Satya P Kunapuli, Laurie E Kilpatrick
Sepsis is characterized by an intense systemic inflammatory response activating a cascade of proinflammatory events resulting in leukocyte dysregulation and host tissue damage. The lung is particularly susceptible to systemic inflammation, leading to acute lung injury. Key to inflammation-induced lung damage is the excessive migration of neutrophils across the vascular endothelium. The mechanisms which regulate neutrophil activation and migration in sepsis are not well defined but there is growing evidence that platelets are actively involved and play a key role in microvascular permeability and neutrophil-mediated organ damage...
2018: PloS One
https://www.readbyqxmd.com/read/29616043/lineage-specific-analysis-of-syk-function-in-autoantibody-induced-arthritis
#11
Tamás Németh, Krisztina Futosi, Kata Szilveszter, Olivér Vilinovszki, Levente Kiss-Pápai, Attila Mócsai
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29614814/the-role-of-single-molecule-force-spectroscopy-in-unraveling-typical-and-autoimmune-heparin-induced-thrombocytopenia
#12
REVIEW
Van-Chien Bui, Thi-Huong Nguyen
For the last two decades, heparins have been widely used as anticoagulants. Besides numerous advantages, up to 5% patients with heparin administration suffer from a major adverse drug effect known as heparin-induced thrombocytopenia (HIT). This typical HIT can result in deep vein thrombosis, pulmonary embolism, occlusion of a limb artery, acute myocardial infarct, stroke, and a systemic reaction or skin necrosis. The basis of HIT may lead to clinical insights. Recent studies using single-molecule force spectroscopy (SMFS)-based atomic force microscopy revealed detailed binding mechanisms of the interactions between platelet factor 4 (PF4) and heparins of different lengths in typical HIT...
April 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29605959/heparin-induced-thrombocytopenia-in-infants-after-heart-surgery
#13
Juma N Abdillah, Qinghua Hu, Xuliang Chen, Xing Chen, Wu Zhou, Wanjun Luo, Lingjin Huang
BACKGROUND:  Heparin-induced thrombocytopenia (HIT) in infants is a rare disorder, and the diagnosis and management of HIT still remains challenging. Argatroban is a synthetic direct thrombin inhibitor (DTI) that is widely used for treating HIT. However, little is known about the efficacy of the activated clotting time (ACT) test in monitoring DTI treatment as an alternative to the routinely used activated partial thromboplastin time (aPTT). METHODS:  Between July 2013 and January 2015, four infants were diagnosed with HIT after surgical correction of congenital anomalies...
April 1, 2018: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/29599195/2-o-3-o-desulfated-heparin-mitigates-murine-chemotherapy-and-radiation-induced-thrombocytopenia
#14
Elizabeth Tkaczynski, Abinaya Arulselvan, John Tkaczynski, Stephen Avery, Liqing Xiao, Beverly Torok-Storb, Kraig Abrams, Narayanam V Rao, Gregory Johnson, Thomas P Kennedy, Mortimer Poncz, Michele P Lambert
Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery...
April 10, 2018: Blood Advances
https://www.readbyqxmd.com/read/29582551/bacterial-killing-by-platelets-making-sense-of-h-it
#15
M F Hoylaerts, T Vanassche, P Verhamme
No abstract text is available yet for this article.
March 27, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29563120/platelet-hmgb1-is-required-for-efficient-bacterial-clearance-in-intra-abdominal-bacterial-sepsis-in-mice
#16
Hui Zhou, Meihong Deng, Yingjie Liu, Chenxuan Yang, Rosemary Hoffman, Jingjiao Zhou, Patricia A Loughran, Melanie J Scott, Matthew D Neal, Timothy R Billiar
Thrombocytopenia impairs host defense and hemostasis in sepsis. However, the mechanisms of how platelets regulate host defense are not fully understood. High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis. Platelets express HMGB1, which is released on activation and has been shown to play a critical role in thrombosis, monocyte recruitment, and neutrophil extracellular trap (NET) production. However, the contribution of platelet HMGB1 to host defense is unknown...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29540475/leukocyte-integrin-mac-1-cd11b-cd18-%C3%AE-m-%C3%AE-2-cr3-acts-as-a-functional-receptor-for-platelet-factor-4
#17
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29531454/the-fondaparinux-paradox-fondaparinux-related-heparin-induced-thrombocytopenia
#18
Sonali Vadi, Vishal Peshattiwar
Fondaparinux, a pentasaccharide administered for heparin-induced thrombocytopenia (HIT), can lead to the occurrence of thrombocytopenia. This patient underwent aortic stent graft placement for Salmonella paratyphi A-infected abdominal aortic aneurysm. Fondaparinux was administered for anticoagulation that led to a dramatic decline in his platelet counts. Investigations revealed HIT profile, PF4/heparin by particle gel immunoassay to be positive. Fondaparinux, a prescribed anticoagulant for HIT can paradoxically predispose to thrombocytopenia...
February 2018: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/29522771/the-contribution-of-chronic-intermittent-hypoxia-to-osahs-from-the-perspective-of-serum-extracellular-microvesicle-proteins
#19
REVIEW
Huina Zhang, Fan Yang, Yichen Guo, Li Wang, Fang Fang, Hao Wu, Shaoping Nie, Yifan Wang, Man-Lung Fung, Yu Huang, Haiteng Deng, Yanwen Qin, Xinliang Ma, Yongxiang Wei
OBJECTIVE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for many clinical complications. However, how OSAHS cause multiple organ injury and initiate inter-organ communication remains unclear. Moreover, despite it is well-recognized that chronic intermittent hypoxia (CIH) is a main feature of OSAHS, specific contribution of CIH to overall OSAHS-initiated pathological complications remains unclear. This study aimed to use an unbiased proteomic approach to determine whether OSAHS alters protein profiles of serum extracellular microvesicles (SEMVs) and how CIH contributes to such alterations...
March 6, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29519941/kinesin-1-is-a-new-actor-involved-in-platelet-secretion-and-thrombus-stability
#20
Frédéric Adam, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-Claude Bordet, Jian-Dong Huang, Marijke Bryckaert, Alain Fischer, Delphine Borgel, Geneviève de Saint Basile, Olivier D Christophe, Gaël Ménasché
OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model...
May 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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