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https://www.readbyqxmd.com/read/28816340/coagulation-factor-xii-regulates-inflammatory-responses-in-human-lungs
#1
Rosanna Hess, Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Gregor Warnecke, Hans-Gerd Fieguth, Steven de Maat, Coen Maas, Francesco Bonella, Klaus T Preissner, Benjamin Weiss, Liliana Schaefer, Wolfgang M Kuebler, Philipp Markart, Malgorzata Wygrecka
Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array...
August 17, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#2
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28804834/one-stage-factor-viii-assays
#3
Elizabeth Duncan, Susan Rodgers
Coagulation factor assays using one-stage methodology are widely used to measure factor levels for the purpose of detecting a deficiency, or to monitor replacement therapy. In this chapter, we focus on a method to measure Factor VIII coagulant activity (FVIII:C) by the one-stage assay (FVIII:C-1), with extra information provided to also allow this method to apply to Factor IX (FIX), Factor XI (FXI), and Factor XII (FXII). From the perspective of laboratory testing, these factors are components of the "intrinsic" coagulation pathway and are all measured in test systems based on the correction of the Activated Partial Thromboplastin Time (APTT)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28798744/the-mast-cell-contact-and-coagulation-system-connection-in-anaphylaxis
#4
REVIEW
Mar Guilarte, Anna Sala-Cunill, Olga Luengo, Moisés Labrador-Horrillo, Victoria Cardona
Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28754139/evidence-of-altered-haemostasis-in-an-ovine-model-of-venovenous-extracorporeal-membrane-oxygenation-support
#5
Margaret R Passmore, Yoke L Fung, Gabriela Simonova, Samuel R Foley, Sara D Diab, Kimble R Dunster, Michelle M Spanevello, Charles I McDonald, John-Paul Tung, Natalie M Pecheniuk, Karen Hay, Kiran Shekar, John F Fraser
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host's haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury...
July 29, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28745506/structure-dependent-hematological-effects-of-per-and-polyfluoroalkyl-substances-on-activation-of-plasma-kallikrein-kinin-system-cascade
#6
Qian S Liu, Yuzhen Sun, Guangbo Qu, Yanmin Long, Xingchen Zhao, Aiqian Zhang, Qunfang Zhou, Ligang Hu, Guibin Jiang
Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28743596/the-plasma-contact-system-a-protease-cascade-at-the-nexus-of-inflammation-coagulation-and-immunity
#7
REVIEW
Henri Weidmann, Laura Heikaus, Andy T Long, Clément Naudin, Hartmut Schlüter, Thomas Renné
The contact system is a potent procoagulant and proinflammatory plasma protease cascade that is initiated by binding ("contact")-induced, auto-activation of factor XII zymogen. Formed active serine protease FXIIa then cleaves plasma prekallikrein to kallikrein that in turn liberates the mediator bradykinin from its precursor high molecular weight kininogen. Bradykinin induces inflammation with implications for host defense and innate immunity. FXIIa also triggers the intrinsic pathway of coagulation that has been shown to critically contribute to thrombosis...
July 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731874/novel-targets-for-anticoagulants-lacking-bleeding-risk
#8
Julia K Bickmann, Trevor Baglin, Joost C M Meijers, Thomas Renné
PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites...
September 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28715096/effect-of-avulsion-storage-media-on-periodontal-ligament-fibroblast-differentiation
#9
İrem Bağ, Sibel Yildirim
BACKGROUND/AIM: An avulsed tooth must be stored in a solution which maintains periodontal ligament (PDL) cell viability. The aim of this study was to compare the effects of Hank's Balanced Salt Solution (HBSS) and milk on the differentiation of PDL fibroblasts. MATERIAL AND METHODS: Eighteen extracted third molars, (n = 3 for each group), were immersed in HBSS, milk, and Dulbecco's Modified Eagle Medium-Ham's F12 (DMEM-F12) at 4 °C for 30-60 min or 12 h. The growth dynamics of PDL fibroblasts were evaluated with cell proliferation graphics and population doubling time (PDT) values...
July 17, 2017: Dental Traumatology: Official Publication of International Association for Dental Traumatology
https://www.readbyqxmd.com/read/28714475/acylated-heptapeptide-binds-albumin-with-high-affinity-and-application-as-tag-furnishes-long-acting-peptides
#10
Alessandro Zorzi, Simon J Middendorp, Jonas Wilbs, Kaycie Deyle, Christian Heinis
The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a 'piggy-back' strategy in which peptides bind via a ligand to the long-lived serum protein albumin. In accordance with this strategy, we developed an easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin (Kd=39 nM)...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28694557/overexpression-of-mir-24-is-involved-in-the-formation-of-hypocoagulation-state-after-severe-trauma-by-inhibiting-the-synthesis-of-coagulation-factor-x
#11
Lu-Jia Chen, Lian Yang, Xing Cheng, Yin-Kai Xue, Li-Bo Chen
BACKGROUND: Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC. METHODS: 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured...
2017: Disease Markers
https://www.readbyqxmd.com/read/28692431/differing-mechanisms-of-thrombin-generation-in-live-haematological-and-solid-cancer-cells-determined-by-calibrated-automated-thrombography
#12
Mufuliat Adeola Adesanya, Anthony Maraveyas, Leigh Madden
: Calibrated automated thrombography (CAT) is emerging as a reliable tool for real-time estimation of thrombin generation potential. There is a clinical need for knowledge about the pathways underlying the thrombotic phenotype of different malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for thrombin generation, using CAT, with the addition of control plasma (NormTrol; Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors VII and XII...
July 7, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28688220/assessment-of-the-protein-interaction-between-coagulation-factor-xii-and-corn-trypsin-inhibitor-by-molecular-docking-and-biochemical-validation
#13
Badraldin K Hamad, Monika Pathak, Rosa Manna, Peter M Fischer, Jonas Emsley, Lodewijk V Dekker
BACKGROUND: Corn trypsin inhibitor (CTI) has selectivity for serine proteases coagulation factor XII (FXII) and trypsin. CTI is in widespread use as a reagent that specifically inhibits the intrinsic pathway of blood coagulation but not the extrinsic pathway. OBJECTIVES: To investigate the molecular basis of FXII inhibition by CTI. METHODS: We performed molecular docking of CTI, using its known crystal structure, with a model of the activated FXII (FXIIa) protease domain...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28661939/interactions-of-%C3%AE-amyloid-peptide-with-fibrinogen-and-coagulation-factor-xii-may-contribute-to-alzheimer-s-disease
#14
Hyung J Ahn, Zu-Lin Chen, Daria Zamolodchikov, Erin H Norris, Sidney Strickland
PURPOSE OF REVIEW: To review the evidence that the Alzheimer peptide β-amyloid interacts with the blood coagulation system and influences the pathophysiology of the disease. RECENT FINDINGS: β-amyloid can interact with fibrinogen and blood coagulation factor XII and trigger ischemia and inflammation. SUMMARY: β-amyloid interacts with fibrinogen and factor XII. These interactions can lead to increased clotting, abnormal clot formation, persistent fibrin deposition, and generation of proinflammatory molecules...
September 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28637352/absence-of-conformational-change-in-complement-factor-3-and-factor-xii-adsorbed-to-acrylate-polymers-is-related-to-a-high-degree-of-polymer-backbone-flexibility
#15
Karin Fromell, Yi Yang, Kristina Nilsson Ekdahl, Bo Nilsson, Mattias Berglin, Hans Elwing
In previous investigations, the authors have examined the adsorption of albumin, immunoglobulin, and fibrinogen to a series of acrylate polymers with different backbone and side-group flexibility. The authors showed that protein adsorption to acrylates with high flexibility, such as poly(lauryl methacrylate) (PLMA), tends to preserve native conformation. In the present study, the authors have continued this work by examining the conformational changes that occur during the binding of complement factor 3 (C3) and coagulation factor XII (FXII)...
June 21, 2017: Biointerphases
https://www.readbyqxmd.com/read/28604413/single-chain-factor-xii-a-new-form-of-activated-factor-xii
#16
Ivan Ivanov, Anton Matafonov, David Gailani
PURPOSE OF REVIEW: Exposure of blood to foreign surfaces induces reciprocal conversion of the plasma proteins factor XII (fXII) and plasma prekallikrein (PPK) to the proteases α-fXIIa and α-kallikrein. This process, called contact activation, has a range of effects on host defence mechanisms, including promoting coagulation. The nature of the triggering mechanism for contact activation is debated. One hypothesis predicts that fXII has protease activity, either intrinsically or upon surface-binding, that initiates contact activation...
September 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28601681/mutation-of-angiopoietin-1-gene-associates-with-a-new-type-of-hereditary-angioedema
#17
Valeria Bafunno, Davide Firinu, Maria D'Apolito, Giorgia Cordisco, Stefania Loffredo, Angelica Leccese, Maria Bova, Maria Pina Barca, Rosa Santacroce, Marco Cicardi, Stefano Del Giacco, Maurizio Margaglione
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease usually due to mutation within the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE no causative variants have been described and the pathophysiology of the disease remains unknown (U-HAE). Identification of causative genes in U-HAE is valuable for understanding the cause of the disease. OBJECTIVE: We conducted genetic studies in Italian patients with U-HAE to identify novel causative genes...
June 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28594426/new-developments-in-anticoagulants-past-present-and-future
#18
Jeffrey I Weitz, Job Harenberg
Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients...
June 28, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28593927/laboratory-characterization-of-leukemic-cell-procoagulants
#19
Renáta Hudák, Ildikó Beke Debreceni, Ivett Deák, Gabriella Gál Szabó, Zsuzsanna Hevessy, Péter Antal-Szalmás, Bjarne Osterud, János Kappelmayer
BACKGROUND: In acute myeloid leukemias, there is an increased chance to develop thrombotic disorders. We hypothesized that in addition to leukemic promyelocytes, monocytic leukemia cells may also have a higher procoagulant activity. METHODS: Fibrin formation was assessed by a one-stage clotting assay using a magnetic coagulometer. The thrombin generation test (TGT) of magnetically isolated normal human monocytes, intact leukemic cells and their isolated microparticles was performed by a fluorimetric assay...
July 26, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28552561/fxii-promotes-proteolytic-processing-of-the-lrp1-ectodomain
#20
Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Peter Braubach, Gregor Warnecke, Hans-Gerd Fieguth, Armin Braun, Günter Lochnit, Philipp Markart, Liliana Schaefer, Malgorzata Wygrecka
BACKGROUND: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described. METHODS: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS)...
August 2017: Biochimica et Biophysica Acta
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