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Coagulation pathways

Maria Sunseri, Tania Ahuja, Tanya Wilcox, David Green
Unfractionated heparin and low-molecular-weight heparins are commonly used as thromboprophylaxis for hospitalized patients. Though generally considered safe at prophylactic doses, cases of catastrophic hemorrhage have been reported. The proposed mechanism involves bioaccumulation of heparin through saturation of the rapid-elimination pathway in its metabolism. We present an unusual case of an average-weight man with metastatic melanoma who suffered hemorrhage with syncope and end-organ damage while on prophylactic three times daily unfractionated heparin...
2018: Case Reports in Hematology
Hui Zhong, Hidenori Wake, Keyue Liu, Yuan Gao, Kiyoshi Teshigawara, Masakiyo Sakaguchi, Shuji Mori, Masahiro Nishibori
The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells...
November 24, 2017: Journal of Pharmacological Sciences
Ilaria Cavazzana, Laura Andreoli, Maarteen Limper, Franco Franceschini, Angela Tincani
PURPOSE OF REVIEW: This review focuses on new clinical aspects of antiphospholipid syndrome (APS) in the last 5 years. RECENT FINDINGS: The pathogenesis of APS is related to endothelial activation by mechanisms other than autoantibody-mediated massive coagulation. These include Toll-like receptors, the m-TORC pathway, and neutrophil activation, inducing an uncontrolled inflammatory cascade. Given these new pathogenetic hypotheses, the treatment of APS could be directed towards a fine balance between anticoagulation and immunomodulation...
March 15, 2018: Current Rheumatology Reports
Jaya Kumar, Srijit Das, Seong Lin Teoh
Acrylamide (AA) is a water soluble white crystalline solid commonly used in industries. It was listed as an industrial chemical with potential carcinogenic properties. However to date, AA was used to produce polyacrylamide polymer, which was widely used as a coagulant in water treatment; additives during papermaking; grouting material for dams, tunnels, and other underground building constructions. AA in food could be formed during high-temperature cooking via several mechanisms, i.e., formation via acrylic acid which may be derived from the degradation of lipid, carbohydrates, or free amino acids; formation via the dehydration/decarboxylation of organic acids (malic acid, lactic acid, and citric acid); and direct formation from amino acids...
2018: Frontiers in Nutrition
Penny S Reynolds, Bernard J Fisher, Jacquelyn McCarter, Christopher Sweeney, Erika J Martin, Paul Middleton, Matthew Ellenberg, Evan Fowler, Donald F Brophy, Alpha A Fowler, Bruce D Spiess, Ramesh Natarajan
BACKGROUND: Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the pro-inflammatory and pro-coagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of polytrauma and hemorrhage. METHODS: Male Sinclair swine (n = 24; mean body weight 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiological monitoring...
March 12, 2018: Journal of Trauma and Acute Care Surgery
Gabriel Sollberger, Dorothea Ogmore Tilley, Arturo Zychlinsky
Neutrophils are essential to the homeostatic mission of safeguarding host tissues, responding rapidly and diversely to breaches of the host's barriers to infection, and returning tissues to a sterile state. In response to specific stimuli, neutrophils extrude modified chromatin structures decorated with specific cytoplasmic and granular proteins called neutrophil extracellular traps (NETs). Several pathways lead to this unique form of cell death (NETosis). Extracellular chromatin may have evolved to defend eukaryotic organisms against infection, and its release has at least three functions: trapping and killing of microbes, amplifying immune responses, and inducing coagulation...
March 12, 2018: Developmental Cell
Fucai Tang, Zhaohui He, Hanqi Lei, Yuehan Chen, Zechao Lu, Guohua Zeng, Hangtao Wang
The purpose of the present study was to identify key genes and investigate the related molecular mechanisms of bladder cancer (BC) progression. From the Gene Expression Omnibus database, the gene expression dataset GSE7476 was downloaded, which contained 43 BC samples and 12 normal bladder tissues. GSE7476 was analyzed to screen the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs using the DAVID database, and a protein‑protein interaction (PPI) network was then constructed using Cytoscape software...
March 9, 2018: Molecular Medicine Reports
Cecilia Augustsson, Anders Svensson, Birgitte Kjaer, Tzu-Yuan Chao, Xia Wenjuan, Berit Olsen Krogh, Jens Breinholt, Jes Thorn Clausen, Ida Hilden, Helle Heibroch Petersen, Lars Christian Petersen
BACKGROUND: Initiation of coagulation is induced by binding of activated factor VII (FVIIa) to tissue factor (TF) and activation of factor X (FX) in a process regulated by tissue factor pathway inhibitor (TFPI). TFPI contains three Kunitz-type protease inhibitor domains (K1-K3) of which K1 and K2 block the active sites of FVIIa and FXa respectively. OBJECTIVE: To produce a monoclonal antibody (mAb) directed towards K1, to characterize the binding epitope, and to study its effect on TFPI inhibition...
March 12, 2018: Journal of Thrombosis and Haemostasis: JTH
Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Mahmoud El-Daly, Darrell Belke, Jonathan L E Dean, Edward R O'Brien, Simon A Hirota, Morley D Hollenberg
BACKGROUND AND PURPOSE: Previously, we demonstrated that exogenous Heat Shock Protein 27 (HSP27/gene, HSPB1) treatment of human endothelial progenitor cells (EPCs) increases the synthesis and secretion of VEGF, improves EPC-migration/re-endothelialization and decreases neo-intima formation, suggesting a role for HSPB1 in regulating EPC function. We hypothesized that HSPB1 could also affect mature endothelial cells (ECs) to alter EC-mediated vasoreactivity in vivo. Our work focused on eNOS/NO-dependent relaxation caused by acetylcholine and the coagulation pathway-activated receptor, proteinase-activated receptor-2 (PAR2)...
March 12, 2018: British Journal of Pharmacology
Nihui Zhang, Ruijuan Yao, Jianglong Guo, Jing He, Guolong Meng, Fang Wu
Chitosan as a natural cationic polysaccharide has drawn wide interests as surface modification materials in orthopedic applications, with the potential to achieve combined osteogenic, antimicrobial and haemostatic functions. The cationicity of chitosan has been reported to play an important role in modifying the osteoblastic cell responses and the antibacterial activities, while its effect on the haemostatic properties has been rarely studied. To this aim, we prepared carboxymethyl chitosan hydrogels with different cationicity through crosslinking with different concentrations of genipin (1%, 2...
February 25, 2018: Colloids and Surfaces. B, Biointerfaces
Paul C Norris, Charles N Serhan
Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels...
March 7, 2018: Biochemical and Biophysical Research Communications
Jenny Chia, Jade Louber, Isabelle Glauser, Shirley Taylor, Greg T Bass, Steve K Dower, Paul A Gleeson, Anne M Verhagen
The neonatal Fc receptor (FcRn) has a pivotal role in albumin and IgG homeostasis. Internalized IgG captured by FcRn under acidic endosomal conditions is recycled to the cell surface where exocytosis and a shift to neutral pH promote extracellular IgG release. Although a similar mechanism is proposed for FcRn-mediated albumin intracellular trafficking and recycling, this pathway is less well defined, but is relevant to the development of therapeutics exploiting FcRn to extend the half-life of short-lived plasma proteins...
March 9, 2018: Journal of Biological Chemistry
Erica Silvestris, Giovanni de Pergola, Raffaele Rosania, Giuseppe Loverro
Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation...
March 9, 2018: Reproductive Biology and Endocrinology: RB&E
Tahereh Mohammadi Majd, Shiva Kalantari, Hadi Raeisi Shahraki, Mohsen Nafar, Afshin Almasi, Shiva Samavat, Mahmoud Parvin, Amirhossein Hashemian
Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study...
March 10, 2018: Iranian Biomedical Journal
Ombretta Repetto, Stefania Maiero, Raffaella Magris, Gianmaria Miolo, Maria Rita Cozzi, Agostino Steffan, Vincenzo Canzonieri, Renato Cannizzaro, Valli De Re
Elevated plasma fibrinogen levels and tumor progression in patients with gastric cancer (GC) have been largely reported. However, distinct fibrinogen chains and domains have different effects on coagulation, inflammation, and angiogenesis. The aim of this study was to characterize fibrinogen β chain (FGB) in GC tissues. Retrospectively we analyzed the data of matched pairs of normal (N) and malignant tissues (T) of 28 consecutive patients with GC at diagnosis by combining one- and two-dimensional electrophoresis (1DE and 2DE) with immunoblotting and mass spectrometry together with two-dimensional difference in gel electrophoresis (2D-DIGE)...
March 7, 2018: International Journal of Molecular Sciences
Massimo Franchini, Pier Mannuccio Mannucci
One of the most challenging issues facing us in the treatment of haemophilia is the development of alloantibodies against infused factor VIII (FVIII) or factor IX (FIX). Inhibitors render factor replacement therapy ineffective, exposing patients to an unacceptably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in a new class of therapeutic agents which act by enhancing coagulation (i...
February 14, 2018: Blood Transfusion, Trasfusione del Sangue
Indranee Rajapreyar, Deepak Acharya, José Tallaj, Lauren Hornbuckle, Jessica Sharpton, Joanna Joly, Salpy Pamboukian
Ventricular arrhythmias occurs in 20-50% of patients supported with left ventricular assist devices (LVAD). Ventricular arrhythmias are well tolerated with LVAD support but long-term consequences include worsening right ventricular function. Management of ventricular arrhythmias in LVAD patients includes use of antiarrhythmic agents or ablation. Amiodarone has been used a first-line agent to treat ventricular arrhythmias post-LVAD implantation. Chronic treatment with amiodarone for arrhythmias can result in hyperthyroidism and hypothyroidism in 5-10% of patients...
March 5, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Edward M Conway
: Complement and coagulation are evolutionarily related proteolytic cascades in the blood that are critical for effecting an appropriate innate response to injury that limits bleeding and infection, while promoting healing. Although often viewed as distinct, it has long been recognized that cross-talk likely exists between these pathways. Only recently have molecular links been established. These are providing insights that are revealing opportunities for the development of novel therapeutic strategies to better treat a wide range of thrombotic, inflammatory, immune, infectious, and malignant diseases...
March 6, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Hua Ye, Shijun Xiao, Xiaoqing Wang, Zhiyong Wang, Zhengshi Zhang, Chengke Zhu, Bingjie Hu, Changhuan Lv, Shuming Zheng, Hui Luo
Schizothorax prenanti (S. prenanti) is an indigenous fish species and is popularly cultured in southwestern China. In recent years, intensive farming of S. prenanti and water quality deterioration has increased the susceptibility of this fish to various pathogens, including Aeromonas hydrophila (A. hydrophila), which has caused severe damage to S. prenanti production. However, the understanding of molecular immune response of S. prenanti to A. hydrophila infection is still lacking. In order to better comprehend the S...
March 8, 2018: Marine Biotechnology
Aster E Pijning, Joyce Chiu, Reichelle X Yeo, Jason W H Wong, Philip J Hogg
Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray structures from bonds that are present in some molecules of a protein crystal but absent in others, or present in some structures of a protein but absent in others. We reasoned that the labile nature of these disulfides signifies a propensity for cleavage and so possible allosteric regulation of the protein in which the bond resides...
February 2018: Royal Society Open Science
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