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"Contact pathway"

Ran Li, Yi-Ming Kuo, Wen-Wen Liu, Cheng-Shin Jang, Enmin Zhao, Liquan Yao
Groundwater contamination with high arsenic (As) levels has caused serious health problem in Jianghan Plain. This study presents a framework to evaluate the results and their probable influencing factors of non-carcinogenic risk and carcinogenic risk in Shahu Village. An appropriate health risk assessment for residents exposing to As through ingestion and dermal contact pathways is also discussed in the paper. Hazard quotient (HQ) and target cancer risk (TR) are adopted to compute the non-carcinogenic and carcinogenic effects for residents, respectively...
February 1, 2018: Environmental Geochemistry and Health
E Campello, M W Henderson, D F Noubouossie, P Simioni, N S Key
Cancer induces a systemic hypercoagulable state that elevates the baseline thrombotic risk of affected patients. This hypercoagulable state reflects a complex interplay between cancer cells and host cells and the coagulation system as part of the host response to cancer. Although the tissue factor (TF)/factor VIIa pathway is proposed to be the principal initiator of fibrin formation in cancer patients, clinical studies have not shown a consistent relationship between circulating TF levels (often measured as plasma microvesicle-associated TF) and the risk of thrombosis...
February 2018: Thrombosis and Haemostasis
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
Maryam Badv, Iqbal H Jaffer, Jeffrey I Weitz, Tohid F Didar
Catheter associated thrombosis is an ongoing problem. Omniphobic coatings based on tethering biocompatible liquid lubricants on self-assembled monolayers of hydrophobic organosilanes attenuate clotting on surfaces. Herein we report an efficient, non-invasive and robust process for coating catheters with an antithrombotic, omniphobic lubricant-infused coating produced using chemical vapor deposition (CVD) of hydrophobic fluorine-based organosilanes. Compared with uncoated catheters, CVD coated catheters significantly attenuated thrombosis via the contact pathway of coagulation...
September 14, 2017: Scientific Reports
Charlotte Bouckaert, Shu Zhu, José W P Govers-Riemslag, Maxime Depoorter, Scott L Diamond, Lionel Pochet
Over the last decade, the coagulation factor XIIa (FXIIa) has seen renewed interest as a therapeutic target. Indeed, its inhibition could offer a protection against thrombosis without increasing the risk of bleeding. Moreover, it could answer the need for a safe prevention of blood-contacting medical devices-related thrombosis. Among the FXII and FXIIa inhibitors already described in literature, organic small-molecular-weight inhibitors are rather left behind. In this study, we were focused on the discovery and assessment of water soluble small molecules...
July 19, 2017: Thrombosis Research
Caroline Gravastrand, Shamal Hamad, Hilde Fure, Bjørg Steinkjer, Liv Ryan, Josè Oberholzer, John D Lambris, Igor Lacík, Tom Eirik Mollnes, Terje Espevik, Ole-Lars Brekke, Anne Mari Rokstad
Alginate microspheres are presently under evaluation for future cell-based therapy. Their ability to induce harmful host reactions needs to be identified for developing the most suitable devices and efficient prevention strategies. We used a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbeads (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules)...
August 2017: Acta Biomaterialia
S Ariane Christie, Lucy Z Kornblith, Benjamin M Howard, Amanda S Conroy, Ryan C Kunitake, Mary F Nelson, Carolyn M Hendrickson, Carolyn S Calfee, Rachael A Callcut, Mitchell Jay Cohen
BACKGROUND: International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation...
June 2017: Journal of Trauma and Acute Care Surgery
Katrijn R Six, Rosalie Devloo, Britt Van Aelst, Philippe Vandekerckhove, Hendrik B Feys, Veerle Compernolle
Microfluidic models of hemostasis assess platelet function under conditions of hydrodynamic shear, but in the presence of anticoagulants, this analysis is restricted to platelet deposition only. The intricate relationship between Ca(2+)-dependent coagulation and platelet function requires careful and controlled recalcification of blood prior to analysis. Our setup uses a Y-shaped mixing channel, which supplies concentrated Ca(2+)/Mg(2+) buffer to flowing blood just prior to perfusion, enabling rapid recalcification without sample stasis...
February 14, 2017: Journal of Visualized Experiments: JoVE
Jeffrey I Weitz, James C Fredenburgh
Compared with vitamin K antagonists, the direct oral anticoagulants (DOACs) are simpler to administer and are associated with less intracranial bleeding. Nonetheless, even with the DOACs, bleeding still occurs and many patients with atrial fibrillation fail to receive anticoagulant thromboprophylaxis because of the fear of bleeding. Therefore, there is an urgent need for safer anticoagulants. Recent investigations into the biochemistry of hemostasis and thrombosis have identified new targets for development of novel anticoagulants...
2017: Frontiers in Medicine
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
Veronique Ollivier, Caroline Roques, Nicolas Receveur, Matthias Gratz, Laurent Feldman, Didier Letourneur, Christian Gachet, Pierre H Mangin, Martine Jandrot-Perrus
Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants...
September 2017: Platelets
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
February 3, 2017: Journal of Biological Chemistry
S M Hassanian, A Avan, A Ardeshirylajimi
Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mammalian target of rapamycin complex-1 (mTORC1) and mTORC2 pathways, respectively. Through interaction with receptor for advanced glycation end products (RAGE) and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins...
February 2017: Journal of Thrombosis and Haemostasis: JTH
Denis F Noubouossie, Matthew F Whelihan, Yuan-Bin Yu, Erica Sparkenbaugh, Rafal Pawlinski, Dougald M Monroe, Nigel S Key
NETosis is a physiologic process in which neutrophils release their nuclear material in the form of neutrophil extracellular traps (NETs). NETs have been reported to directly promote thrombosis in animal models. Although the effects of purified NET components including DNA, histone proteins, and neutrophil enzymes on coagulation have been characterized, the mechanism by which intact NETs promote thrombosis is largely unknown. In this study, human neutrophils were stimulated to produce NETs in platelet-free plasma (PFP) or in buffer using phorbol myristate actetate or calcium ionophore...
February 23, 2017: Blood
Yuanzheng Zhai, Xiaobing Zhao, Yanguo Teng, Xiao Li, Junjun Zhang, Jin Wu, Rui Zuo
In order to learn the pollution circumstance of groundwater nitrate detailedly in Songnen Plain of Northeast China and estimate its potential risk to human health of local residents, a total of 389 groundwater samples were collected in 2014 and studied from residential areas and public water supply wells in 11 cities and counties in southeastern of Songnen Plain. The analysis results showed that the spatial distributions of main chemical components in groundwater had great variations with statistical concentrations in the order of TDS> HCO3> Ca> NO3> Cl> Na> SO4> Mg> K> NH4> NO2...
March 2017: Ecotoxicology and Environmental Safety
Lisha Lin, Mingyi Wu, Jinhua Zhao
The plasma contact system sits atop the intrinsic coagulation cascade and plasma kallikrein-kinin pathway, and in vivo its activation contributes, respectively, to coagulation and inflammation mainly via two downstream pathways. This system has been widely investigated, its activation mechanisms by negatively charged surfaces and the interactions within its components, factor XII, prekallikrein and high molecular weight kininogen are well understood at the biochemical level. However, as most of the activators that have been discovered by in vitro experiments are exogenous, the physiological activators and roles of the contact system have remained unclear and controversial...
March 2017: International Journal of Hematology
M Gissel, K E Brummel-Ziedins, S Butenas, A E Pusateri, K G Mann, T Orfeo
BACKGROUND: Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood lead to aberrant coagulation require further elucidation. OBJECTIVE: To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. METHODS: Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: 1) Tissue factor (TF)-initiated coagulation proteome mixtures (± factor (F)XI, ± fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; 2) Enzyme/inhibitor reactions; 3) TF-dependent or -independent clot dynamics in contact pathway inhibited blood via viscoelastometry...
July 19, 2016: Journal of Thrombosis and Haemostasis: JTH
Haiyun Wu, Qilin Liao, Steven N Chillrud, Qiang Yang, Lei Huang, Jun Bi, Beizhan Yan
Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks...
July 14, 2016: Scientific Reports
Alexander J Donovan, Joseph Kalkowski, Magdalena Szymusiak, Canhui Wang, Stephanie A Smith, Robert F Klie, James H Morrissey, Ying Liu
Granular platelet-sized polyphosphate nanoparticles (polyP NPs) were encapsulated in sterically stabilized liposomes, forming a potential, targeted procoagulant nanotherapy resembling human platelet dense granules in both structure and functionality. Dynamic light scattering (DLS) measurements reveal that artificial dense granules (ADGs) are colloidally stable and that the granular polyP NPs are encapsulated at high efficiencies. High-resolution scanning transmission electron microscopy (HR-STEM) indicates that the ADGs are monodisperse particles with a 150 nm diameter dense core consisting of P, Ca, and O surrounded by a corrugated 25 nm thick shell containing P, C, and O...
August 8, 2016: Biomacromolecules
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