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https://www.readbyqxmd.com/read/28102766/soluble-p-selectin-rescues-mice-from-anthrax-lethal-toxin-induced-mortality-through-psgl-1-pathway-mediated-correction-of-hemostasis
#1
Der-Shan Sun, Yao-Wen Chang, Jyh-Hwa Kau, Hsin-Hsien Huang, Pei-Hsun Ho, Yin-Jeh Tzeng, Hsin-Hou Chang
As one of the virulence factors of Bacillus anthracis, lethal toxin (LT) induces various pathogenic responses including the suppression of the coagulation system. In this study, we observed that LT markedly increased the circulating soluble P-selectin (sP-sel) levels and microparticle (MP) count in wild-type but not P-selectin (P-sel, Selp(-)(-)(-)) or P-sel ligand-1 (PSGL-1, Selplg(-)(-)(-)) knockout mice. Because sP-sel induces a hypercoagulable state through PSGL-1 pathway to generate tissue factor-positive MPs, we hypothesized that the increase in plasma sP-sel levels can be a self-rescue response in hosts against the LT-mediated suppression of the coagulation system...
January 19, 2017: Virulence
https://www.readbyqxmd.com/read/28099190/coagulation-imbalance-and-neurocognitive-functioning-in-older-hiv-adults-on-suppressive-antiretroviral-therapy
#2
Jessica L Montoya, Jennifer Iudicello, Hannah A Oppenheim, Pariya L Fazeli, Michael Potter, Qing Ma, Paul J Mills, Ronald J Ellis, Igor Grant, Scott L Letendre, David J Moore
OBJECTIVES: To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. DESIGN: Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. METHODS: Participants completed standardized neurobehavioral and neuromedical assessments...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28097631/force-dependent-calcium-signaling-and-its-pathway-of-human-neutrophils-on-p-selectin-in-flow
#3
Bing Huang, Yingchen Ling, Jiangguo Lin, Xin Du, Ying Fang, Jianhua Wu
P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy...
January 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28097236/lung-vaso-occlusion-in-sickle-cell-disease-mediated-by-arteriolar-neutrophil-platelet-microemboli
#4
Margaret F Bennewitz, Maritza A Jimenez, Ravi Vats, Egemen Tutuncuoglu, Jude Jonassaint, Gregory J Kato, Mark T Gladwin, Prithu Sundd
In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096486/phage-derived-protein-induces-increased-platelet-activation-and-is-associated-with-mortality-in-patients-with-invasive-pneumococcal-disease
#5
Rahajeng N Tunjungputri, Fredrick M Mobegi, Amelieke J Cremers, Christa E van der Gaast-de Jongh, Gerben Ferwerda, Jacques F Meis, Nel Roeleveld, Stephen D Bentley, Alexander S Pastura, Sacha A F T van Hijum, Andre J van der Ven, Quirijn de Mast, Aldert Zomer, Marien I de Jonge
: To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28092426/incomplete-reversibility-of-platelet-inhibition-following-prolonged-exposure-to-ticagrelor
#6
A J Gerrits, J A Jakubowski, A Sugidachi, A D Michelson, A L Frelinger
INTRODUCTION: Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). METHODS: Whole blood was treated in vitro with ~50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28090293/relevance-of-angiopoietin-2-and-soluble-p-selectin-levels-in-patients-with-pulmonary-arterial-hypertension-receiving-combination-therapy-with-oral-treprostinil-a-freedom-c2-biomarker-substudy
#7
Manuel J Richter, Ralph Schermuly, Werner Seeger, Youlan Rao, Hossein A Ghofrani, Henning Gall
: Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin (sP-selectin) as biomarkers of disease severity and treatment response in pulmonary arterial hypertension (PAH), but additional data are required for validation. We evaluated these biomarkers using data from FREEDOM-C2, in which patients with PAH receiving stable monotherapy or combination therapy were randomized to receive additional treatment with oral treprostinil (up-titrated from 0.25 mg twice daily) or placebo for 16 weeks...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28087905/-inflammatory-cytokines-and-oxidative-stress-markers-in-the-inhibition-of-osteoarthritis-by-curcumin
#8
Jun Liu, Xiaole He, Ping Zhen, Shenghu Zhou, Xusheng Li
Objective: To observe the influence of matrix metalloproteinases-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), CD47, L-selectin and advanced oxidation proteinproducts (AOPP) in osteoarthritis and the intervention of curcumin. Methods: A total of 20 male C57BL/6 mice (10.05-15.00 g) were randomly divided into control group, OA group, Cur25 group and Cur50 group (intraperitoneal injected 25 μmol/L or 50 μmol/L of curcumin everyday after modeling). After 4 weeks treatment, we observed the morphological changes of the gross specimen by immunohistochemical method, and observed the ultrastructure of cartilage tissue under electron microscope...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28081301/ethanol-induces-platelet-apoptosis
#9
Lei Liu, Mengxing Chen, Lili Zhao, Qing Zhao, Renping Hu, Jie Zhu, Rong Yan, Kesheng Dai
BACKGROUND: Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis. METHODS: Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected...
January 12, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28067100/effects-of-a-single-bout-of-strenuous-exercise-on-platelet-activation-in-female-apoe-ldlr-mice
#10
K Przyborowski, H Kassassir, M Wojewoda, K Kmiecik, B Sitek, K Siewiera, A Zakrzewska, A M Rudolf, R Kostogrys, C Watala, J A Zoladz, S Chlopicki
Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI2) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR(-)(/-) mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice...
January 9, 2017: Platelets
https://www.readbyqxmd.com/read/28052584/activated-platelet-derived-and-leukocyte-derived-circulating-microparticles-and-the-risk-of-thrombosis-in-heparin-induced-thrombocytopenia-a-role-for-pf4-bearing-microparticles
#11
Elena Campello, Claudia M Radu, Elena Duner, Anna M Lombardi, Luca Spiezia, Raffaele Bendo, Silvia Ferrari, Paolo Simioni, Fabrizio Fabris
BACKGROUND: Though the presence of platelets-derived microparticles (MPs) have previously been described in heparin-induced thrombocytopenia (HIT), the mechanism of thrombosis in HIT remains poorly understood. We aimed to asses the presence and origin of MPs in patients with HIT and their possible contribution to HIT with thrombosis (HITT). METHODS: Forty-five patients with HIT and 45 matched hospitalized patients with not confirmed HIT (HIT-negative) were enrolled...
January 3, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28051279/carotid-intima-media-thickness-and-blood-biomarkers-of-atherosclerosis-in-patients-after-stroke-or-myocardial-infarction
#12
Iwona Kurkowska-Jastrzebska, Michał A Karlinski, Beata Błazejewska-Hyzorek, Iwona Sarzynska-Dlugosz, Krzysztof J Filipiak, Anna Czlonkowska
AIM: To test if circulating levels of markers of inflammation, endothelial function, and chronic infections, as well as association between these markers and carotid intima media thickness (CIMT), depend on the stage of atherosclerosis expressed as a history of a major vascular event. METHODS: The associations were analyzed separately in 75 healthy controls, 79 patients 3-6 months after the first-ever non-cardioembolic ischemic stroke (IS), and 37 patients 3-6 months after the first-ever myocardial infarction (MI)...
December 31, 2016: Croatian Medical Journal
https://www.readbyqxmd.com/read/28045880/targeted-complement-inhibition-protects-vascularized-composite-allografts-from-acute-graft-injury-and-prolongs-graft-survival-when-combined-with-subtherapeutic-cyclosporine-a-therapy
#13
Peng Zhu, Stefanie R Bailey, Biao Lei, Chrystal M Paulos, Carl Atkinson, Stephen Tomlinson
BACKGROUND: Recipients of vascularized composite allografts require aggressive and life-long immunosuppression, and since the surgery is usually performed in nonlife threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. METHODS: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry)...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28044245/mri-detection-of-endothelial-cell-inflammation-using-targeted-superparamagnetic-particles-of-iron-oxide-spio
#14
Joyce M S Chan, Maggie S H Cheung, Richard G J Gibbs, Kishore K Bhakoo
BACKGROUND: There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells. METHODS: The in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28041985/associations-between-inflammation-related-biomarkers-and-depressive-symptoms-in-individuals-with-recently-diagnosed-type-1-and-type-2-diabetes
#15
Christian Herder, Jan-Felix Fürstos, Bettina Nowotny, Alexander Begun, Klaus Strassburger, Karsten Müssig, Julia Szendroedi, Andrea Icks, Michael Roden
Depressive disorders represent a frequent comorbidity of both type 1 (T1D) and type 2 diabetes (T2D). Inflammation-related processes have been implicated in the development of both diabetes and depression. This study aimed to investigate whether biomarkers of subclinical inflammation were associated with depressive symptoms in individuals with recently diagnosed diabetes and if such associations differed by diabetes type. This cross-sectional study was based on 295 individuals with T2D (67% men, mean age 53years) and 139 individuals with T1D (60% men, mean age 36years) of the German Diabetes Study...
December 29, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28034759/targeting-p-selectin-glycoprotein-ligand-1-p-selectin-interactions-as-a-novel-therapy-for-metabolic-syndrome
#16
REVIEW
Madhukar S Patel, David Miranda-Nieves, Jiaxuan Chen, Carolyn A Haller, Elliot L Chaikof
Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28033029/higher-platelet-reactivity-and-platelet-monocyte-complex-formation-in-gram-positive-sepsis-compared-to-gram-negative-sepsis
#17
Rahajeng N Tunjungputri, Wouter van de Heijden, Rolf T Urbanus, Philip G de Groot, Andre van der Ven, Quirijn de Mast
Platelets may play a role in the high risk for vascular complications in Gram-positive sepsis. We compared the platelet reactivity of 15 patients with Gram-positive sepsis, 17 with Gram-negative sepsis and 20 healthy controls using a whole blood flow cytometry-based assay. Patients with Gram-positive sepsis had the highest median fluorescence intensity (MFI) of the platelet membrane expression of P-selectin upon stimulation with high dose adenosine diphosphate (ADP; P = 0.002 vs. Gram-negative and P = 0.005 vs...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28031335/nkg2c-e-marks-the-unique-cytotoxic-cd4-t-cell-subset-thctl-generated-by-influenza-infection
#18
Nikki B Marshall, Allen M Vong, Priyadharshini Devarajan, Matthew D Brauner, Yi Kuang, Ribhu Nayar, Elizabeth A Schutten, Catherine H Castonguay, Leslie J Berg, Stephen L Nutt, Susan L Swain
CD4 T cells can differentiate into multiple effector subsets, including ThCTL that mediate MHC class II-restricted cytotoxicity. Although CD4 T cell-mediated cytotoxicity has been reported in multiple viral infections, their characteristics and the factors regulating their generation are unclear, in part due to a lack of a signature marker. We show in this article that, in mice, NKG2C/E identifies the ThCTL that develop in the lung during influenza A virus infection. ThCTL express the NKG2X/CD94 complex, in particular the NKG2C/E isoforms...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28031221/molecular-magnetic-resonance-imaging-discloses-endothelial-activation-after-transient-ischaemic-attack
#19
Aurélien Quenault, Sara Martinez de Lizarrondo, Olivier Etard, Maxime Gauberti, Cyrille Orset, Benoît Haelewyn, Helen C Segal, Peter M Rothwell, Denis Vivien, Emmanuel Touzé, Carine Ali
SEE SUN ET AL DOI101093/AWW306 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: About 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack...
January 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28029329/tissue-factor-as-a-predictor-of-recurrent-venous-thromboembolism-in-malignancy-biomarker-analyses-of-the-catch-trial
#20
Alok A Khorana, Pieter W Kamphuisen, Guy Meyer, Rupert Bauersachs, Mette S Janas, Mikala F Jarner, Agnes Y Y Lee
Purpose Circulating tissue factor (TF) has been studied as a biomarker for predicting initial, but not recurrent, venous thromboembolism (VTE) in cancer, a setting in which predictors are incompletely understood. We evaluated the association of TF, clinical risk factors, and other biomarkers measured at the time of initial VTE with recurrent VTE in a prespecified analysis of the CATCH (Comparison of Acute Treatments in Cancer Hemostasis) trial. Methods CATCH was a randomized, multicenter trial that investigated tinzaparin 175 IU/kg once daily or dose-adjusted warfarin for 6 months in patients with cancer and acute, symptomatic VTE...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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