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Anti platelet

Dong Liu, Jie-Lu Zhou, Fashui Hong, Yu-Qing Zhang
Titanium dioxide nanoparticles (TiO2 NPs) are used in many fields, such as paints, medicine additives, food additives, sunscreens and agriculture. The aim of this study was to investgate the mechanism behind the formation of inflammation induced by TiO2 NPs. ICR mice were exposed to TiO2 NPs through intragastric administration at 2.5, 5 and 10 mg/kg body weight every day for 90 consecutive days. The experiment suggested that long-term exposure to TiO2 NPs resulted in an obvious inflammatory response in mice lung tissues, which led to a thickened alveoli septum, lung hyperaemia, and titanium accumulation...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Da-Shi Qi, Jin-Hao Tao, Lian-Qin Zhang, Mei Wang, Rui Qu, Lian-Qin Zhang, Pei Liu, Jian-Cheng Miu, Jing-Yi Ma, Xin-Yu Mei
Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats...
October 18, 2016: Brain Research
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
María T Álvarez-Román, Ihosvany Fernández-Bello, Víctor Jiménez-Yuste, Mónica Martín-Salces, Elena G Arias-Salgado, María I Rivas Pollmar, Raúl Justo Sanz, Nora V Butta
Despite their low platelet count some immune thrombocytopenia (ITP) patients seldom bleed, indicating the presence of factors to compensate thrombocytopenia. Moreover, ITP patients may have an increased risk for thrombosis. These facts suggest the presence of procoagulant mechanisms that have not been clarified yet. The aim of this study was to identify these possible factors. Moreover, the utility of rotational thromboelastometry (ROTEM(®) ) to test haemostasis in these patients was also evaluated. Patients with ITP presented a procoagulant profile due to an increased amount of platelet- and red cell-microparticles, an increased resistance to protein C and the formation of a clot more resistant to fibrinolysis due to augmented levels of plasminogen activator inhibitor-1, which might reflect an endothelial damage/activation in ITP patients...
October 21, 2016: British Journal of Haematology
Janina Jamasbi, Remco T A Megens, Mariaelvy Bianchini, Kerstin Uhland, Götz Münch, Martin Ungerer, Shachar Sherman, Alexander Faussner, Richard Brandl, Christine John, Johannes Buchner, Christian Weber, Reinhard Lorenz, Natalie Elia, Wolfgang Siess
To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc), the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG). Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes...
April 2016: JACC. Basic to Translational Science
Carol H Miao
Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect...
2016: Thrombosis Journal
Xiaohong Ruby Xu, Naadiya Carrim, Miguel Antonio Dias Neves, Thomas McKeown, Tyler W Stratton, Rodrigo Matos Pinto Coelho, Xi Lei, Pingguo Chen, Jianhua Xu, Xiangrong Dai, Benjamin Xiaoyi Li, Heyu Ni
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i...
2016: Thrombosis Journal
Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
Nicholas W Russo, Giovanna Petrucci, Bianca Rocca
Low-dose aspirin, alone or in combination, is recommended for the secondary prevention of acute non-cardioembolic ischemic stroke and transient ischemic attack, starting soon after the acute event. Clinically-relevant drug-drug interactions (DDIs) are a major concern of regulatory agencies and practicing physicians. Drug's pharmacodynamics and/or pharmacokinetics account for clinically-relevant DDIs that modify efficacy and/or safety of one or more of the co-administered drugs. Some non-steroidal anti-inflammatory drugs interact with aspirin pharmacodynamics by competing on the drug target, i...
October 17, 2016: Vascular Pharmacology
Daniela D'Arcangelo, Francesco Facchiano, Giovanni Nassa, Andrea Stancato, Annalisa Antonini, Stefania Rossi, Cinzia Senatore, Martina Cordella, Claudio Tabolacci, Annamaria Salvati, Roberta Tarallo, Alessandro Weisz, Angelo M Facchiano, Antonio Facchiano
Melanoma is the most aggressive skin-cancer, showing high mortality at advanced stages. Platelet Derived Growth Factor Receptor-alpha (PDGFR-alpha) potently inhibits melanoma- and endothelium-proliferation and its expression is significantly reduced in melanoma-biopsies, suggesting that melanoma progression eliminates cells expressing PDGFR-alpha. In the present study transient overexpression of PDGFR-alpha in endothelial (HUVEC) and melanoma (SKMel-28, A375, Preyer) human-cells shows strong anti-proliferative effects, with profound transcriptome and miRNome deregulation...
October 13, 2016: Oncotarget
Hye Seon Kang, Chin Kook Rhee, Hea Yon Lee, Hyoung Kyu Yoon, Soon Seok Kwon, Sook Young Lee
Background/Aims: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling...
October 20, 2016: Korean Journal of Internal Medicine
Jih-Jung Chen, Tung-Han Tsai, Hsiang-Ruei Liao, Li-Chai Chen, Yueh-Hsiung Kuo, Ping-Jyun Sung, Chun-Lin Chen, Chun-Sheng Wei
Two new sesquiterpenoids-13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)-have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3-15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
J C Menon, J K Joseph, M P Jose, B L Dhananjaya, O V Oommen
INTRODUCTION: Snakebite is an occupational hazard causing considerable morbidity and mortality worldwide, particularly so in tropical countries like India. OBJECTIVE: The aim of this study is to (i) review the demographic, clinical and laboratory findings in patients (1051) admitted with venomous snakebite (ii) to correlate mortality, morbidity and duration of hospital stay with clinical signs, symptoms and laboratory parameters. METHODS: A retrospective study of 1051 patients treated for snakebite over 10 years (2000 - 2009) in Little Flower Hospital, Angamaly, Kerala...
August 2016: Journal of the Association of Physicians of India
Mojtaba Shafiekhani, Pouya Faridi, Javad Kojuri, Soha Namazi
OBJECTIVE: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. MATERIALS AND METHODS: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0...
September 2016: Avicenna Journal of Phytomedicine
H Zöllner, R Jouni, S Panzer, A Khadour, L Janzen, J Wesche, M Ten Berg, S Schellong, A Heinken, A Greinacher, T Bakchoul
BACKGROUND: Protamine (PRT) is used to stabilize insulin in Neutral Protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin-complexes is common in diabetic patients. OBJECTIVES: To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. METHODS: The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays...
October 19, 2016: Journal of Thrombosis and Haemostasis: JTH
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
R Muñoz-Cano, E Ainsua-Enrich, I Torres-Atencio, M Martin, J Sánchez-Lopez, J Bartra, C Picado, J Mullol, A Valero
RATIONALE: Platelet activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, such as the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with demonstrated anti-PAF effect but its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. OBJECTIVE: To investigate the ability of rupatadine to inhibit PAF-induced MC degranulation compared with desloratadine and levocetirizine, to confirm dual rupatadine anti-H1 and anti-PAF activities...
October 19, 2016: Journal of Investigational Allergology & Clinical Immunology
Silvia Riondino, Fiorella Guadagni, Vincenzo Formica, Patrizia Ferroni, Mario Roselli
Venous thromboembolism (VTE) is a commonly diagnosed multifactorial condition with significant morbidity and mortality, occurring in up to 20% of cancer patients. Indeed, patients with cancer are in a higher pro-thrombotic state due to alterations in their haemostatic-coagulative system, stasis and blood flow slowdown, endothelial dysfunction, vascular inflammation and platelet activation. Moreover, several cancer-dependent factors can sum up to trigger a first episode of VTE or to cause its recurrence in the course of anticoagulant treatment...
October 18, 2016: Current Medicinal Chemistry
Mayank Sardana, Matthew Moll, Harrison W Farber
Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
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