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https://www.readbyqxmd.com/read/28109047/novel-antiplatelet-role-for-a-protein-disulfide-isomerase-targeted-peptide-evidence-of-covalent-binding-to-c-terminal-cghc-redox-motif
#1
H R Sousa, R S Gaspar, E M L Sena, S A da Silva, J L de L Fontelles, T L S Araújo, M Mastrogiovanni, D M Fries, A P S Azevedo-Santos, F R M Laurindo, A Trostchansky, A M Paes
Protein disulfide isomerase (PDI) plays a major role in platelet aggregation and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized this peptide would also inhibit platelet aggregation by association to surface PDI. Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109042/expression-and-characterization-of-a-codon-optimized-blood-coagulation-factor-viii
#2
S A Shestopal, J-J Hao, E Karnaukhova, Y Liang, M V Ovanesov, M Lin, J H Kurasawa, T K Lee, J H McVey, A G Sarafanov
BACKGROUND: Production of recombinant factor VIII (FVIII) is challenging due to its low expression. It was previously shown that codon-optimization of a B domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well-recognized that synonymous mutations may affect the protein structure and function. OBJECTIVES: To compare biochemical properties of a BDD-FVIII expressed from codon-optimized (CO) and the wild-type (WT) cDNAs. METHODS: Each variant of the BDD-FVIII was expressed in several independent CHO cell lines, generated using a lentiviral platform...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28108578/the-activated-clotting-time-in-cardiac-surgery-should-celite-or-kaolin-be-used
#3
Adrianus J De Vries, Annemieke Oude Lansink-Hartgring, Freek-Jan Fernhout, Rolf C G Huet, Edwin R van den Heuvel
OBJECTIVES: Both kaolin- and Celite-activated clotting times (ACT) are used to guide anticoagulation during cardiopulmonary bypass. It is unknown whether these methods lead to similar management procedures for anticoagulation in patients and are thus interchangeable in terms of bias, precision and variability. METHODS: We randomized 97 patients undergoing coronary artery bypass grafting or aortic valve replacement to either kaolin- or Celite-guided anticoagulation...
January 20, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28107924/effective-covalent-immobilization-of-quinone-and-aptamer-onto-a-gold-electrode-via-thiol-addition-for-sensitive-and-selective-protein-biosensing
#4
Zhaohong Su, Haitao Xu, Xiaolin Xu, Yi Zhang, Yan Ma, Chaorong Li, Qingji Xie
Effective covalent immobilization of quinone and aptamer onto a gold electrode via thiol addition (a Michael addition) for sensitive and selective protein (with thrombin as the model) biosensing is reported, with a detection limit down to 20 fM for thrombin. Briefly, the thiol addition reaction of a gold electrode-supported 1,6-hexanedithiol (HDT) with p-benzoquinone (BQ) yielded BQ-HDT/Au, and the similar reaction of thiolated thrombin aptamer (TTA) with activated BQ-HDT/Au under 0.3V led to formation of a gold electrode-supported novel electrochemical probe TTA-BQ-HDT/Au...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28105835/silver-nanoclusters-beacon-as-stimuli-responsive-versatile-platform-for-multiplex-dnas-detection-and-aptamer-substrate-complexes-sensing
#5
Guoliang Liu, Jingjing Li, Da-Qian Feng, Jun-Jie Zhu, Wei Wang
An activatable silver nanoclusters beacon (ASNCB) was synthesized through a facile one-pot approach and applied for multiplex DNAs, small molecule, and protein sensing. Multifunctional single-stranded DNA sequences are rationally designed and used for ASNCB in situ synthesis. Via target-responsive structure transformation of ASNCB, target recognition induced ASNCB conformational transition and lit up the fluorescent signal of silver nanoclusters. By further implementing two different color ASNCBs (520 and 600 nm), the parallel multiplexed analysis of two target genes (Influenza A virus genes H1N1 and H5N1) is achieved...
January 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28105561/the-rise-and-fall-of-anticoagulation-with-bivalirudin-during-percutaneous-coronary-interventions-a-review-article
#6
REVIEW
Constantinos Andreou, Christos Maniotis, Michael Koutouzis
Bivalirudin is a direct thrombin inhibitor used during percutaneous coronary intervention (PCI). Treatment with bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPI) reduced bleeding complications, but resulted in higher rates of ischemic events, including acute stent thrombosis in ST segment elevation myocardial infarction (STEMI) patients. Thus, it may be considered a reasonable alternative antithrombotic agent in patients at high risk of bleeding undergoing PCI. However its superiority over heparin alone is questioned particularly in the era of novel antiplatelet agents and transradial PCI...
January 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28103989/-experimental-research-on-the-effects-of-different-activators-on-the-formation-of-platelet-rich-gel-and-the-release-of-bioactive-substances-in-human-platelet-rich-plasma
#7
Y Yang, W Zhang, B Cheng
Objective: To explore the effects of calcium gluconate and thrombin on the formation of platelet-rich gel (PRG) and the release of bioactive substances in human platelet-rich plasma (PRP) and the clinical significance. Methods: Six healthy blood donors who met the inclusion criteria were recruited in our unit from May to August in 2016. Platelet samples of each donor were collected for preparation of PRP. (1) PRP in the volume of 10 mL was collected from each donor and divided into thrombin activation group (TA, added with 0...
January 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28103832/thromboelastometry-analysis-of-thrombocytopenic-dengue-patients-a-cross-sectional-study
#8
Felipe Maia de Toledo Piza, Thiago Domingos Corrêa, Alexandre Rodrigues Marra, João Carlos Campos Guerra, Roseny Dos Reis Rodrigues, Andrea Aparecida Rocco Villarinho, Valdir Fernandes de Aranda, Sandra Christina Pereira Lima Shiramizo, Maria Roza de Jesus de Lima, Esper Georges Kallas, Alexandre Biasi Cavalcanti
BACKGROUND: Dengue virus infection (DVI) is a prevalent and potentially fatal viral disease associated with coagulopathy. So far, the coagulation profile of DVI patients with thrombocytopenia has not been assessed through a viscoelastic test such as rotational thromboelastometry. We aimed to describe the prevalence and characteristics of coagulation abnormalities in dengue fever outpatients with thrombocytopenia, addressed by both rotational thromboelastometry and conventional coagulation tests...
January 19, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28102751/extracellular-vesicles-from-activated-platelets-a-semiquantitative-cryo-electron-microscopy-and-immuno-gold-labeling-study
#9
Alain R Brisson, Sisareuth Tan, Romain Linares, Céline Gounou, Nicolas Arraud
Cells release membrane vesicles in their surrounding medium either constitutively or in response to activating signals. Two main types of extracellular vesicles (EVs) are commonly distinguished based on their mechanism of formation, membrane composition and size. According to the current model, EVs shed from the plasma membrane, often called microvesicles, expose phosphatidylserine (PS) and range in size from 100 nm to 1 µm, while EVs originating from endosomal multi-vesicular bodies, called exosomes, contain tetraspanin proteins, including CD63, and range in size from 50 to 100 nm...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28102740/update-on-functional-and-genetic-laboratory-assays-for-the-detection-of-platelet-microvesicles
#10
Maxime Laroche, Claire Dunois, Anne Marie Vissac, Jean Amiral
Functional and genetic assays for measuring platelet microvesicles (PMVs) are presented and discussed. Functional assays concern two groups of methods: a) homogeneous assays using the cofactor activity of phospholipids (PPLs) contained in PMVs and present in assayed plasmas, and a coagulation or a thrombin generation assay (TGA) as "end points"; b) capture-based assays, in which PMVs bind to an immobilized ligand, such as Annexin V in the presence of calcium, or monoclonal antibodies (MoAbs) specific for membrane proteins...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28101869/fibrin-formation-structure-and-properties
#11
John W Weisel, Rustem I Litvinov
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28100695/mapping-the-affinity-landscape-of-thrombin-binding-aptamers-on-2-f-ana-dna-chimeric-g-quadruplex-microarrays
#12
Jory Lietard, Hala Abou Assi, Irene Gómez-Pinto, Carlos González, Mark M Somoza, Masad J Damha
In situ fabricated nucleic acids microarrays are versatile and very high-throughput platforms for aptamer optimization and discovery, but the chemical space that can be probed against a given target has largely been confined to DNA, while RNA and non-natural nucleic acid microarrays are still an essentially uncharted territory. 2'-Fluoroarabinonucleic acid (2'F-ANA) is a prime candidate for such use in microarrays. Indeed, 2'F-ANA chemistry is readily amenable to photolithographic microarray synthesis and its potential in high affinity aptamers has been recently discovered...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28098698/clinical-and-practical-aspects-of-restoring-thrombin-generation-in-acute-coagulopathic-bleeding
#13
Kenichi A Tanaka, Daniel Bolliger, Nina A Guzzetta
No abstract text is available yet for this article.
February 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#14
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28095402/a-general-shear-dependent-model-for-thrombus-formation
#15
Alireza Yazdani, He Li, Jay D Humphrey, George Em Karniadakis
Modeling the transport, activation, and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions. We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro experimental data and can be used over a wide range of flow shear rates ([Formula: see text]). We introduce an Eulerian-Lagrangian model where hemodynamics is solved on a fixed Eulerian grid, while platelets are tracked using a Lagrangian framework...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28094003/recombinant-thrombomodulin-suppresses-tumor-growth-of-pancreatic-cancer-by-blocking-thrombin-induced-par1-and-nf-%C3%AE%C2%BAb-activation
#16
Yoshihiro Shirai, Tadashi Uwagawa, Hiroaki Shiba, Yohta Shimada, Takashi Horiuchi, Nobuhiro Saito, Kenei Furukawa, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Thrombomodulin, an anticoagulant that inhibits thrombin-induced growth factor promotion, also has an anti-inflammatory effect. Furthermore, thrombomodulin inhibits nuclear factor-kappa B activation, which plays a crucial role in cancer progression. We assessed the antitumor activity of recombinant thrombomodulin for pancreatic cancer. METHODS: A xenograft orthotopic model was established in mice by implantation of human pancreatic cancer cells. The animals were treated with intraperitoneal injection of recombinant thrombomodulin 5 times a week for 4 weeks...
January 13, 2017: Surgery
https://www.readbyqxmd.com/read/28092405/thrombin-contributes-to-protective-immunity-in-pneumonia-derived-sepsis-via-fibrin-polymerization-and-platelet-neutrophil-interactions
#17
Theodora A M Claushuis, Sacha F de Stoppelaar, Ingrid Stroo, Joris J T H Roelofs, Roelof Ottenhoff, Tom van der Poll, Cornelis van 't Veer
BACKGROUND: Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental for outcome due to microvascular failure but can also enhance host defense. The role of thrombin herein has not been fully elucidated. OBJECTIVE: We aimed to investigate the contribution of thrombin to the host response during pneumonia derived sepsis. METHODS: Mice treated with the specific thrombin inhibitor Dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28090594/effects-of-tranexamic-acid-on-platelet-function-and-thrombin-generation-etaplat-woman-trial-sub-study
#18
Kastriot Dallaku, Haleema Shakur, Ian Roberts, Phil Edwards, Danielle Beaumont, Maria Delius, Braun Siegmund, Orion Gliozheni, Ilir Tasha, Saimir Cenameri, Ulrich Mansmann
Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets.  Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH.  Methods. We will conduct a sub-study within the WOMAN trial...
December 15, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28088496/endogenous-thrombin-potential-changes-during-the-first-cycle-of-oral-contraceptive-use
#19
Carolyn L Westhoff, Malcolm C Pike, Serge Cremers, Andrew Eisenberger, Stella Thomassen, Jan Rosing
OBJECTIVES: Venous thromboembolism (VTE) risk increases within months of combination oral contraceptive (COC) initiation. Because elevated endogenous thrombin potential (ETP) has been found in several studies to be a VTE risk factor, we evaluated the extent of ETP changes during the initial cycle of an ethinyl estradiol (EE) and levonorgestrel (LNG) COC. We also assessed the relationship between ETP changes and systemic EE and LNG concentrations. STUDY DESIGN: Participants provided multiple blood samples during a first 21-day cycle of a 30 μg EE/150 μg LNG COC and after a further 7 days without an active COC...
January 11, 2017: Contraception
https://www.readbyqxmd.com/read/28081301/ethanol-induces-platelet-apoptosis
#20
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
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