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Coagulation cascade

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https://www.readbyqxmd.com/read/28213103/expression-and-characterization-of-haemathrins-madanin-like-thrombin-inhibitors-isolated-from-the-salivary-gland-of-tick-haemaphysalis-bispinosa-acari-ixodidae
#1
Rajeev Kungur Brahma, Guillaume Blanchet, Simran Kaur, R Manjunatha Kini, Robin Doley
Saliva of hematophagous animals, such as ticks, is an excellent source of anticoagulant proteins and polypeptides. Here we describe the identification and characterization of two thrombin inhibitors named as haemathrin 1 and 2 from the salivary gland of tick Haemaphysalis bispinosa using genomic approach. Haemathrins are cysteine-less peptide anticoagulants, which share about 65-70% identity with madanins, and belong to inhibitor I53 superfamily of inhibitors of the MEROPS database. Haemathrins were overexpressed in E...
January 31, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28199731/proteomic-profiling-analysis-reveals-a-link-between-experimental-autoimmune-uveitis-and-complement-activation-in-rats
#2
Dadong Guo, Bing Hu, Hongying Tang, Yuanyuan Sun, Bin Liu, Qingmei Tian, Hongsheng Bi
Uveitis is an autoimmune disease that usually damages the vision function, leading to poor visual quality in patients. As an autoimmune ocular inflammatory disease, the pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signaling pathways. Nevertheless, the detailed mechanism remains unclear. In this study, we induced an experimental autoimmune uveitis (EAU) model in rats. We determined the levels of C3a and membrane attack complex C5b-9 (soluble C5b-9, sC5b-9) in both plasma and aqueous humor, identified the differentially expressed proteins in plasma by liquid chromatography-tandem mass spectrometry, and employed bioinformatics algorithms to analyze differentially expressed proteins in EAU rat plasma...
February 15, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28196659/sutures-impregnated-with-carbazate-activated-polyvinyl-alcohol-reduce-intraperitoneal-adhesions
#3
F Fredriksson, F Sellberg, T Bowden, T Engstrand, D Berglund, H E Lilja
BACKGROUND: Intraperitoneal adhesions cause significant morbidity. They occur after peritoneal trauma, which induces oxidative stress with production of inflammatory cytokines, peroxidized proteins (carbonyls) and lipids (aldehydes). This study aimed to investigate if carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl inhibitor, can reduce intraperitoneal adhesions in an experimental model. MATERIAL AND METHODS: Male Sprague-Dawley rats (n=110) underwent laparotomy, cecal abrasion and construction of a small bowel anastomosis...
February 1, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28181317/ace-inhibitors-may-interfere-with-omalizumab-in-chronic-spontaneous-urticaria
#4
Riccardo Asero
The extrinsic pathway of coagulation cascade is activated in chronic spontaneous urticaria (CSU), and such activation parallels disease severity (1). D-dimer levels are elevated in cases resistant to antihistamines (2) and/or cyclosporine (3). Omalizumab is highly effective in most patients with severe, antihistamine-resistant CSU. Two cases of severe CSU in which ACE-inhibitor was associated with the loss of response to omalizumab are reported. This article is protected by copyright. All rights reserved.
February 9, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28176468/correlation-of-pre-operative-plasma-protein-concentrations-in-cardiac-surgery-patients-with-bleeding-outcomes-using-a-targeted-quantitative-proteomics-approach
#5
Nathan Clendenen, Ashley Tollefson, Monika Dzieciatkowska, Alice Cambiaghi, Manuela Ferrario, Miranda Kroehl, Anirban Banerjee, Angelo D'Alessandro, Kirk C Hansen, Nathaen Weitzel
PURPOSE: Despite recent advancements in the use of thrombelastography (TEG) in the surgical setting, adequate technology to accurately predict bleeding phenotypes for patients undergoing cardiopulmonary bypass on the basis of non-mechanical parameters is lacking. While basic science and translational studies have provided key mechanistic insights about the protein components of coagulation cascades and regulatory mediators of hemostasis and fibrinolysis, targeted protein assays are still missing and the association of protein profiles to bleeding phenotypes and TEG readouts have yet to be discovered...
February 8, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28166139/novel-injury-site-targeted-fusion-protein-comprising-annexin-v-and-kunitz-inhibitor-domains-ameliorates-ischemia-reperfusion-injury-and-promotes-survival-of-ischemic-rat-abdominal-skin-flaps
#6
Victor Bong-Hang Shyu, Chung En Hsu, Chih-Jen Wen, Tze-Chein Wun, Rui Tang, Samuel Achilefu, Fu-Chan Wei, Hui-Yun Cheng
: Appropriate antithrombotic therapy is critical for successful outcomes in reconstructive microsurgical procedures involving free tissue transfer. The annexin V-6L15 (ANV-6L15) fusion protein was developed as a targeted antithrombotic reagent. Annexin V specifically binds to exposed phosphatidylserine on apoptotic or injured cells, and prevents coagulation and cell adhesion, whereas 6L15 inhibits tissue factor-VIIa pathway within the coagulation cascade. The treatment efficacy of ANV-6L15 on rat island muscle and pedicled abdominal fasciocutaneous flaps following ischemic injury and ischemia-reperfusion injury (IRI) was evaluated...
February 4, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28161438/molecular-and-evolutionary-perspectives-of-the-renin-angiotensin-system-from-lamprey
#7
Marty K S Wong, Yoshio Takei
The recent advance and revision on the renin-angiotensin system in lamprey were summarized and we emphasized that presence of two types of angiotensins (Angs) in lamprey. Due to the parasitic nature on fish blood, teleost-type Angs were produced in their buccal gland and secreted into the lamphredin to evade the host immunorejection. A native lamprey angiotensinogen (AGT) was identified in genome and it retains serine-protease inhibitor activity for thrombin that regulates the blood coagulation pathway. The native lamprey angiotensin II (Lp-Ang II) is hypotensive instead of hypertensive, suggesting a functional divergence on cardiovascular regulation from the main vertebrate groups...
February 2, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28160197/much-more-than-trousseau-syndrome-the-broad-spectrum-of-the-pancreatic-paraneoplastic-syndromes
#8
REVIEW
Attila Zalatnai, Eszter Perjési, Eszter Galambos
When 150 years ago Armand Trousseau proposed that some thrombotic events might be the first sign of concealed visceral malignancies, these findings seemed to be just of anecdotal interest. Since then, however, we have learned that adenocarcinomas, including pancreatic cancers could be associated with a wide spectrum of paraneoplastic syndromes. They may precede the detection of the tumor, may occur simultaneously or may develop during its progression. Due to various hematologic, endocrine, cutaneous, articular, neuromuscular, renal or even psychiatric syndromes, their correct interpretation is intriguing, and because their early signs are not necessarily recognized first by oncologists, the paraneoplastic syndromes pose a diagnostic challenge...
February 3, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28159709/role-of-the-plasma-cascade-systems-in-ischemia-reperfusion-injury-of-bone
#9
Shengye Zhang, Carlos Wotzkow, Anjan K Bongoni, Jane Shaw-Boden, Mark Siegrist, Adriano Taddeo, Fabian Blank, Willy Hofstetter, Robert Rieben
Ischemia/reperfusion (I/R) injury has been extensively studied in organs such as heart, brain, liver, kidney, and lung. As a vascularized organ, bone is known to be susceptible to I/R injury too, but the respective mechanisms are not well understood to date. We therefore hypothesized that, similar to other organs, plasma cascade-induced inflammation also plays a role in bone I/R injury. Reperfusion injury in rat tibia was induced by unilateral clamping of the femoral artery and additional use of a tourniquet, while keeping the femoral vein patent to prevent venous congestion...
January 31, 2017: Bone
https://www.readbyqxmd.com/read/28150568/structural-modulation-of-factor-viia-by-full-length-tissue-factor-tf1-263-implication-of-novel-interactions-between-egf2-domain-and-tf
#10
Ramesh Prasad, Prosenjit Sen
Tissue factor (TF)-mediated factor VII (FVII) activation and subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As the result of unresolved crystal structure of the full-length TF1-263-FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear...
February 2, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28150310/plasma-treated-with-amotosalen-and-ultraviolet-a-light-retains-activity-for-hemostasis-after-5-days-post-thaw-storage-at-1-to-6-o-c
#11
Anna Erickson, Katie Waldhaus, Tovo David, Norman Huang, Salvador Rico, Laurence Corash, Nina Mufti, Richard J Benjamin
BACKGROUND: Plasma thawed and stored at 1 to 6(°) C for up to 5 days (thawed plasma [TP]) provides rapid availability in emergencies and reduces plasma waste, but it carries risks of coagulation factor loss or activation, bacterial outgrowth, and viral contamination. We characterized changes in amotosalen/ultraviolet A (UVA) light pathogen-reduced, fresh-frozen plasma (FFP) and plasma frozen within 24 hours (PF24) with post-thaw storage. STUDY DESIGN AND METHODS: Amotosalen/UVA light-treated FFP and PF24 were thawed after approximately 3 to more than 12 months of frozen storage and held at 1 to 6(°) C for 5 days...
February 1, 2017: Transfusion
https://www.readbyqxmd.com/read/28144242/complement-in-pancreatic-disease-perpetrator-or-savior
#12
REVIEW
Lucas Bettac, Stephanie Denk, Thomas Seufferlein, Markus Huber-Lang
The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28130261/impact-of-thrombosis-on-pulmonary-endothelial-injury-and-repair-following-sepsis
#13
Colin Evans, You-Yang Zhao
The prevailing morbidity and mortality in sepsis are largely due to multiple organ dysfunction (MOD), most commonly lung injury, as well as renal and cardiac dysfunction. Despite recent advances in defining many aspects of the pathogenesis of sepsis-related MOD, including acute respiratory distress syndrome (ARDS), there are currently no effective pharmacological or cell-based treatments for the disease. Human and animal studies have shown that pulmonary thrombosis is common in sepsis-induced ARDS, and pre-clinical studies have shown that anti-coagulation may improve outcome following sepsis challenge...
January 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28123102/the-minipig-is-a-suitable-non-rodent-model-in-the-safety-assessment-of-single-stranded-oligonucleotides
#14
A Braendli-Baiocco, M Festag, K Dumong-Erichsen, R Persson, M J Mihatsch, N Fisker, J Funk, S Mohr, R Constien, C Ploix, K Brady, M Berrera, B Altmann, B Lenz, M Albassam, G Schmitt, T Weiser, F Schuler, T Singer, Y Tessier
Non-human primates (NHPs) are currently considered to be the non-rodent species of choice for the preclinical safety assessment of single-stranded oligonucleotide (SSO) drugs. We evaluated minipigs as a potential alternative to NHPs to test the safety of this class of compounds. Four different phosphorothioated locked nucleic acid (LNA)-based SSOs (three antisense and one anti-miR), all with known safety profiles, were administered to minipigs using similar study designs and read-outs as in earlier NHP studies with the same compounds...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28120727/antiplatelet-agents-and-anticoagulants-from-pharmacology-to-clinical-practice
#15
Maria E Tsoumani, Alexandros D Tselepis
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#16
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28102737/platelet-microvesicles-in-health-and-disease
#17
Imene Melki, Nicolas Tessandier, Anne Zufferey, Eric Boilard
Interest in cell-derived extracellular vesicles and their physiological and pathological implications is constantly growing. Microvesicles, also known as microparticles, are small extracellular vesicles released by cells in response to activation or apoptosis. Among the different microvesicles present in the blood of healthy individuals, platelet-derived microvesicles (PMVs) are the most abundant. Their characterization has revealed a heterogeneous cargo that includes a set of adhesion molecules. Similarly to platelets, PMVs are also involved in thrombosis through support of the coagulation cascade...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28095402/a-general-shear-dependent-model-for-thrombus-formation
#18
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/28089408/the-various-assays-for-measuring-activity-states-of-factor-viia-in-plasma-and-therapeutic-products-diagnostic-value-and-analytical-usefulness-in-various-pathophysiological-states
#19
REVIEW
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms...
December 29, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28079978/targeting-coagulation-factor-receptors-protease-activated-receptors-in-idiopathic-pulmonary-fibrosis
#20
REVIEW
C Lin, K Borensztajn, C A Spek
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate of > 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, i.e. nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease, and do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF have identified several possible targets for therapeutic interventions...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
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