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https://www.readbyqxmd.com/read/27913422/factor-xi-deficiency-enhances-the-pulmonary-allergic-response-to-house-dust-mite-in-mice-independent-of-factor-xii
#1
Ingrid Stroo, Jack Yang, Johannes Daan de Boer, Joris J T H Roelofs, Cornelis van 't Veer, Francis J Castellino, Sacha Zeerleder, Tom van der Poll
Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system, and its possible route of activation, in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO) and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27888641/carotid-artery-and-lower-cranial-nerve-exposure-with-increasing-surgical-complexity-to-the-parapharyngeal-space
#2
Ana M Lemos-Rodriguez, Satyan B Sreenath, Rounak B Rawal, Lewis J Overton, Zainab Farzal, Adam M Zanation
OBJECTIVES/HYPOTHESIS: To investigate the extent of carotid artery exposure attained, including the identification of the external carotid branches and lower cranial nerves in five sequential external approaches to the parapharyngeal space, and to provide an anatomical algorithm. STUDY DESIGN: Anatomical study. METHODS: Six latex-injected adult cadaver heads were dissected in five consecutive approaches: transcervical approach with submandibular gland removal, posterior extension of the transcervical approach, transcervical approach with parotidectomy, parotidectomy with lateral mandibulotomy, and parotidectomy with mandibulectomy...
November 26, 2016: Laryngoscope
https://www.readbyqxmd.com/read/27867935/processing-of-factor-xii-during-inflammatory-reactions
#3
REVIEW
Bernard Nico Jukema, Steven de Maat, Coen Maas
The contact system was originally identified as an obsolete part of the coagulation system, but it has been repeatedly implicated in inflammatory states, such as infection, as well as in allergic- and chronic inflammatory disease. Under these conditions, there is surprisingly little evidence that factor XII (FXII) acts as a coagulation factor, and its activity appears to be mainly directed toward activation of the kallikrein-kinin system. The contact system factors interact with pathogens as well as cells of the (innate) immune system on several levels...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27862752/improving-the-binding-affinity-of-in-vitro-evolved-cyclic-peptides-by-inserting-atoms-into-the-macrocycle-backbone
#4
Jonas Wilbs, Simon J Middendorp, Christian Heinis
Cyclic peptides binding to targets of interest can be generated efficiently with powerful in vitro display techniques, such as phage display or mRNA display. The cyclic peptide libraries screened with these methods are generated by altering in a combinatorial fashion the amino acid sequence of the peptides, the number of amino acids in the macrocycle rings, and the cyclization chemistry. A structural element that cannot easily be varied in the cyclic peptides is the backbone, which is built from amino acids, each of which contributes three atoms to the macrocyclic ring structure...
November 11, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27848184/the-initiation-and-effects-of-plasma-contact-activation-an-overview
#5
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...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27836023/coagulation-factor-abnormalities-related-to-discordance-between-anti-factor-xa-and-activated-partial-thromboplastin-time-in-patients-supported-with-continuous-flow-left-ventricular-assist-devices
#6
Sirtaz Adatya, Roy Sunny, Megan J Fitzpatrick, Monica Colvin, Thennapan Thennapan, Ranjit John, Nicole Dodge Zantek, Marc Pritzker, Peter Eckman, Nir Uriel
BACKGROUND: High levels of discordance between activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-FXa) have been reported in patients with continuous-flow left ventricular assist devices (CF-LVADs). We sought to determine the biochemical basis for discordance by simultaneous measurement of coagulation factors with aPTT and anti-FXa. METHODS: Consecutive CF-LVAD patients admitted for intravenous unfractionated heparin (IV-UFH) therapy were studied...
November 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27834692/factor-xii-as-a-therapeutic-target-in-thromboembolic-and-inflammatory-diseases
#7
REVIEW
Katrin F Nickel, Andy T Long, Tobias A Fuchs, Lynn M Butler, Thomas Renné
Coagulation factor XII (FXII, Hageman factor) is a plasma protease that in its active form (FXIIa) initiates the procoagulant and proinflammatory contact system. This name arises from FXII's unique mechanism of activation that is induced by binding (contact) to negatively charged surfaces. Various substances have the capacity to trigger FXII contact-activation in vivo including mast cell-derived heparin, misfolded protein aggregates, collagen, nucleic acids, and polyphosphate. FXII deficiency is not associated with bleeding, and for decades, the factor was considered to be dispensable for coagulation in vivo...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27829580/inhibitory-effect-of-ethinylestradiol-on-coagulation-factors-in-rats
#8
Yanira Franco-Murillo, Ruth Jaimez
Epidemiological and experimental data have indicated the beneficial and adverse effects of estrogenic replacement therapy. In the present study, we explored the effect of ethinylestradiol (EE) and 17β-estradiol (E2) on screening tests, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as the activity of coagulation factors (FVII, FX, FXI, and FXII) in male Wistar rats. Animals were injected subcutaneously during three consecutive days with EE or E2 (1, 3, 10, and 30 mg/kg) and propylene glycol (0...
November 9, 2016: Experimental Animals
https://www.readbyqxmd.com/read/27829262/-upper-airway-stimulation-in-osa
#9
B Bender
Anatomical basis of obstructive sleep apnea (OSA) is the collapse of the pharynx during sleep. It is considered as a result of complex interactions of structural and neuromuscular factors. Depth of sleep and body position have modulating effects. Although different areas of obstruction were identified, studies show that the sleep-mediated obstruction frequently occurs in the base of tongue area.Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea syndrome (OSAS) since more than 30 years...
November 2016: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/27826093/cytokine-and-estrogen-stimulation-of-endothelial-cells-augment-activation-of-the-prekallikrein-high-molecular-weight-kininogen-complex-implications-for-hereditary-angioedema-hae
#10
Kusumam Joseph, Baby G Tholanikunnel, Allen P Kaplan
BACKGROUND: When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein due to release of heat shock protein-90 (Hsp90). While bradykinin formation is typically initiated by factor XII autoactivation it is also possible to activate factor XII either by kallikrein, thus formed, or plasmin. RATIONALE: Since attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation...
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27786338/coagulation-factor-xii-induces-pro-inflammatory-cytokine-responses-in-macrophages-and-promotes-atherosclerosis-in-mice
#11
Sandra Vorlova, Miriam Koch, Helga D Manthey, Clement Cochain, Martin Busch, Sweena M Chaudhari, David Stegner, Manuel Yepes, Kristina Lorenz, Marc W Nolte, Bernhard Nieswandt, Alma Zernecke
Atherosclerosis is considered a chronic inflammatory disease of the vessel wall. Coagulation pathways and immune responses contribute to disease development. The role of coagulation factor XII (FXII) in vascular inflammation, however, remains controversial. We here investigated the function of FXII in atherosclerosis using apolipoprotein E and FXII-deficient (F12(-/-)Apoe(-/-)) mice. Compared to F12(+/+)Apoe(-/-) controls, atherosclerotic lesion formation was reduced in F12(-/-)Apoe(-/-) mice. This was associated with a decrease in serum interleukin (IL)-1β and IL-12 levels and reduced expression of pro-inflammatory cytokines in the aorta in atherosclerotic F12(-/-)Apoe(-/-) mice, as well as diminished Th1-cell differentiation in the aorta, blood, and lymphoid organs...
October 27, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27782339/the-complement-and-contact-activation-systems-partnership-in-pathogenesis-beyond-angioedema
#12
REVIEW
Berhane Ghebrehiwet, Allen P Kaplan, Kusumam Joseph, Ellinor I B Peerschke
The blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar "initiating trigger" followed by sequential and cascade-like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein-kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross-talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27780803/emerging-anticoagulant-strategies
#13
James C Fredenburgh, Peter L Gross, Jeffrey I Weitz
Despite the introduction of direct oral anticoagulants (DOACs), the search for more effective and safer antithrombotic strategies continues. Better understanding of the pathogenesis of thrombosis has fostered two new approaches to achieving this goal. First, evidence that thrombin may be as important as platelets to thrombosis at sites of arterial injury and that platelets contribute to venous thrombosis has prompted trials comparing anticoagulants with aspirin for secondary prevention in arterial thrombosis and aspirin with anticoagulants for primary and secondary prevention of venous thrombosis...
October 25, 2016: Blood
https://www.readbyqxmd.com/read/27777753/coagulative-safety-of-epidural-catheters-after-major-upper-gastrointestinal-surgery-advanced-and-routine-coagulation-analysis-in-38-patients
#14
Owain Thomas, Hampus Rein, Karin Strandberg, Ulf Schött
BACKGROUND: The risk of spinal haematoma in patients receiving epidural catheters is estimated using routine coagulation tests, but guidelines are inconsistent in their recommendations on what to do when results indicate slight hypocoagulation. Postoperative patients are prone to thrombosis, and thromboelastometry has previously shown hypercoagulation in this setting. We aimed to better understand perioperative haemostasis by comparing results from routine and advanced tests, hypothesizing that patients undergoing major upper gastrointestinal surgery would be deficient in vitamin K-dependent coagulation factors because of malnutrition, or hypocoagulative because of accumulation of low molecular weight heparin (LMWH)...
2016: Perioperative Medicine
https://www.readbyqxmd.com/read/27694320/polyphosphate-co-localizes-with-factor-xii-on-platelet-bound-fibrin-and-augments-its-plasminogen-activator-activity
#15
Joanne L Mitchell, Ausra S Lionikiene, Georgi Georgiev, Anja Klemmer, Chelsea Brain, Paul Y Kim, Nicola J Mutch
Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared to urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100-mer) and platelet-derived polyP, significantly augment the plasminogen activation capacity of αFXIIa...
September 30, 2016: Blood
https://www.readbyqxmd.com/read/27685458/an-update-on-the-pharmaceutical-management-of-thrombosis
#16
Benilde Cosmi
Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs. Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes...
October 12, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27637310/the-intrinsic-pathway-of-coagulation-as-a-target-for-antithrombotic-therapy
#17
REVIEW
Allison P Wheeler, David Gailani
Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI, and IX. While this series of proteolytic reactions is not an accurate model for hemostasis in vivo, there is mounting evidence that factor XI and factor XII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a small effect on hemostasis. This article discusses the contributions of components of the intrinsic pathway to thrombosis in animal models and humans, and results of early clinical trials of drugs targeting factors IX, XI, and XII...
October 2016: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27609313/disulfide-bond-pattern-of-transforming-growth-factor-%C3%AE-induced-protein
#18
Marie V Lukassen, Carsten Scavenius, Ida B Thøgersen, Jan J Enghild
Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein composed of an NH2-terminal cysteine-rich domain (CRD) annotated as an emilin (EMI) domain and four fasciclin-1 (FAS1-1-FAS1-4) domains. Mutations in the gene cause corneal dystrophies, a group of debilitating protein misfolding diseases that lead to severe visual impairment. Previous studies have shown that TGFBIp in the cornea is cross-linked to type XII collagen through a reducible bond. TGFBIp contains 11 cysteine residues and is thus able to form five intramolecule disulfide bonds, leaving a single cysteine residue available for the collagen cross-link...
October 4, 2016: Biochemistry
https://www.readbyqxmd.com/read/27596064/neutralizing-blood-borne-polyphosphate-in-vivo-provides-safe-thromboprotection
#19
Linda Labberton, Ellinor Kenne, Andy T Long, Katrin F Nickel, Antonio Di Gennaro, Rachel A Rigg, James S Hernandez, Lynn Butler, Coen Maas, Evi X Stavrou, Thomas Renné
Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow...
September 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27581227/von-willebrand-factor-and-prekallikrein-in-plasma-are-associated-with-thrombus-volume-in-abdominal-aortic-aneurysms
#20
Qasam M Ghulam, Kim K Bredahl, Jørgen B Gram, Lars Lönn, Jens P Goetze, Henrik H Sillesen, Jonas P Eiberg
OBJECTIVES: Disruption of the endothelial lining may be one of the events linking intraluminal thrombus and abdominal aortic aneurysm growth. In the present study, we examined whether von Willebrand factor activity in plasma, contact proteins of blood coagulation, and inflammatory biomarkers may be associated with intraluminal thrombus volume in search of a biochemical marker of endothelial damage and thrombus size. DESIGN: Prospective study, correlating potential endothelial biomarkers and intraluminal thrombus volume acquired by computed tomography angiography...
August 2016: Vascular and Endovascular Surgery
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