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thrombomodulin

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https://www.readbyqxmd.com/read/28930996/assessment-of-the-anticoagulant-and-anti-inflammatory-properties-of-endothelial-cells-using-3d-cell-culture-and-non-anticoagulated-whole-blood
#1
Riccardo Sfriso, Anjan Bongoni, Yara Banz, Nikolai Klymiuk, Eckhard Wolf, Robert Rieben
In vivo, endothelial cells are crucial for the natural anticoagulation of circulating blood. Consequently, endothelial cell activation leads to blood coagulation. This phenomenon is observed in many clinical situations, like organ transplantation in the presence of pre-formed anti-donor antibodies, including xenotransplantation, as well as in ischemia/reperfusion injury. In order to reduce animal experimentation according to the 3R standards (reduction, replacement and refinement), in vitro models to study the effect of endothelial cell activation on blood coagulation would be highly desirable...
September 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930238/a-thrombomodulin-gene-polymorphism-c1418t-is-associated-with-early-outcomes-in-patients-undergoing-coronary-artery-bypass-graft-surgery-with-a-conventional-cardiopulmonary-bypass-during-hospitalization
#2
Ching-Chou Pai, Yi-Wen Lin, Yi-Ting Tsai, Shih-Hurng Loh, Chih-Yuan Lin, Chin-Sheng Lin, Yi-Chang Lin, Hung-Yen Ke, Feng-Yen Lin, Chien-Sung Tsai
Background: Thrombomodulin (TM) is a type of cell membrane-bound anticoagulant protein cofactor in the thrombin-mediated activation of protein C. Previous evidence has shown an association between TM polymorphisms and systemic inflammation. Conventional cardiopulmonary bypass (CPB), beating-heart CPB, and off-pump techniques have been widely used in cardiac surgery. However, these techniques may also cause systemic inflammatory responses in the patients. Whether TM polymorphisms are associated with systemic inflammation after cardiac surgery is still unclear...
April 23, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28920104/variable-phenotypic-penetrance-of-thrombosis-in-adult-mice-after-tissue-selective-and-temporally-controlled-thbd-gene-inactivation
#3
Thijs E van Mens, Hai-Po H Liang, Sreemanti Basu, Irene Hernandez, Mark Zogg, Jennifer May, Min Zhan, Qiuhui Yang, Jamie Foeckler, Shawn Kalloway, Rashmi Sood, Caren Sue Karlson, Hartmut Weiler
Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/28888219/factor-xa-inhibition-by-rivaroxaban-in-the-trough-steady-state-can-significantly-reduce-thrombin-generation
#4
Shigeo Horinaka, Rie Sugawara, Yutaka Yonezawa, Toshihiko Ishimitsu
AIMS: The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. METHODS: A single-centre, prospective, non-randomised, drug intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with non-valvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and anti-factor Xa chromogenic assay...
September 9, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28885470/poor-microcirculatory-flow-dynamics-are-associated-with-endothelial-cell-damage-and-glycocalyx-shedding-following-traumatic-hemorrhagic-shock
#5
David N Naumann, Jon Hazeldine, Mark J Midwinter, Sam D Hutchings, Paul Harrison
BACKGROUND: Endothelial cell damage and glycocalyx shedding following trauma can increase the risk of inflammation, coagulopathy, vascular permeability and death. Bedside sublingual video-microscopy may detect worse flow and perfusion associated with this endotheliopathy. We compared markers of endotheliopathy with physical flow dynamics following traumatic hemorrhagic shock (THS). METHODS: Sublingual incident dark field video-microscopy was performed at three time-points following injury (<10h; 10-30h; and 30-50h)...
September 5, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28872471/lung-xenotransplantation
#6
Hisashi Sahara, Hironosuke Watanabe, Thomas Pomposelli, Kazuhiko Yamada
PURPOSE OF REVIEW: This review describes the most recent progress in xeno lung transplantation (XLTx) to date. It describes the potential mechanisms of early xeno lung graft loss, as well as the latest therapeutic strategies to overcome them. RECENT FINDINGS: Using ex-vivo perfusion models of porcine lungs with human blood, the use of genetically modified pig lungs along with novel pharmaceutical approaches has recently been studied. Strategies that have demonstrated improved lung survival include the knockout of known xenoantigens (GalTKO and N-glycolylneuraminic acid-KO), genes that regulate complement activation (hCD46 and hCD55), as well as the inflammation/coagulation cascade (human leukocyte antigen-E, human thrombomodulin, human endothelial protein C receptor, hCD47, hCD39, hCD73 and heme oxygenase-1)...
September 1, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28868636/plasma-levels-of-haemostatic-factors-in-patients-with-pulmonary-embolism-on-admission-and-seven-months-later
#7
M Sane, M Granér, J A Laukkanen, V-P Harjola, P Mustonen
INTRODUCTION: With the exception of D-dimer, not much is known about the plasma levels of haemostatic factors during acute venous thromboembolism (VTE) compared to their basic levels in a stable phase. The goal of this study was to examine how plasma levels of factor V, VIII, XIIIa, von Willebrand factor antigen (vWF:Ag), fibrinogen, thrombomodulin evolve from the point of diagnosis of acute VTE to the end of standard treatment period. METHODS: Sixty-three consecutive patients (mean 57, range 18-86 years, 33 females) with acute pulmonary embolism (PE) were included...
September 4, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28852519/fatal-diffuse-alveolar-haemorrhage-mimicking-acute-exacerbation-in-idiopathic-pulmonary-fibrosis-treated-with-nintedanib
#8
Keishi Sugino, Yasuhiko Nakamura, Muneyuki Sekiya, Hiroshi Kobayashi, Kazutoshi Shibuya, Sakae Homma
A 75-year-old man was referred to our hospital with a 1-year history of persistent dry cough and progressive dyspnoea on exertion. He was treated with aspirin due to thrombosis of internal carotid artery. He was diagnosed with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), and started on inhaled N-acetylcysteine therapy and pirfenidone. Since his clinical condition progressively deteriorated after 6 months, he was switched from pirfenidone to nintedanib. As a result, his general condition worsened rapidly...
November 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28843665/balanced-haemostasis-with-both-hypo-and-hyper-coagulable-features-in-critically-ill-patients-with-acute-on-chronic-liver-failure
#9
Caleb Fisher, Vishal C Patel, Sidsel Hyldgaard Stoy, Arjuna Singanayagam, Jelle Adelmeijer, Julia Wendon, Debbie L Shawcross, Ton Lisman, William Bernal
BACKGROUND: Cirrhotic patients have complex haemostatic abnormalities. Current evidence suggests stable cirrhotic (SC) patients have a "re-balanced" haemostatic state. However, limited data exists in acute decompensated (AD) or acute on chronic liver failure (ACLF) patients. METHODS: We utilised thrombin generation analysis, fibrinolysis assessment, and evaluation of haemostatic parameters to assess haemostasis in liver disease of progressive severity. RESULTS: The study cohorts were comprised of: SC, n=8; AD n=44; ACLF, n=17; and Healthy Control (HC), n=35...
August 17, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28841902/markers-of-acute-kidney-injury-in-patients-with-sepsis-the-role-of-soluble-thrombomodulin
#10
Shinshu Katayama, Shin Nunomiya, Kansuke Koyama, Masahiko Wada, Toshitaka Koinuma, Yuya Goto, Ken Tonai, Jun Shima
BACKGROUND: Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. METHODS: We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016...
August 25, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28834363/decreased-expression-of-thrombomodulin-in-endothelial-cells-by-fibroblast-growth-factor-23-%C3%AE-klotho
#11
Kenji Tanaka, Tancharoen Salunya, Yoshihiro Motomiya, Yasuki Motomiya, Yoko Oyama, Munekazu Yamakuchi, Ikuro Maruyama
Chronic kidney disease (CKD) has been known to be a state of excessive fibroblast growth factor-23 (FGF23) and α-Klotho deficiency. Patients undergoing hemodialysis have an increased mortality risk associated with cardiovascular disease and endothelial dysfunction. The mechanism responsible for the relationship of FGF23 to endothelial damage in these patients has been unclear. On the other hands, increasing evidences have demonstrated that thrombomodulin (TM) plays an important role in the endothelial barrier...
August 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28829810/extracellular-overhydration-linked-with-endothelial-dysfunction-in-the-context-of-inflammation-in-haemodialysis-dependent-chronic-kidney-disease
#12
Nicos Mitsides, Tom Cornelis, Natascha J H Broers, Nanda M P Diederen, Paul Brenchley, Frank M van der Sande, Casper G Schalkwijk, Jeroen P Kooman, Sandip Mitra
BACKGROUND: Haemodialysis (HD) patients are predisposed to dysregulated fluid balance leading to extracellular water (ECW) expansion. Fluid overload has been closely linked with outcome in these patients. This has mainly been attributed to cardiac volume overload, but the relation between abnormalities in fluid status with micro- and macrovascular dysfunction has not been studied in detail. We studied the interaction of macro- and microvascular factors in states of normal and over- hydration in HD-dependent CKD...
2017: PloS One
https://www.readbyqxmd.com/read/28827518/activated-protein-c-protects-from-gvhd-via-par2-par3-signalling-in-regulatory-t-cells
#13
Satish Ranjan, Alexander Goihl, Shrey Kohli, Ihsan Gadi, Mandy Pierau, Khurrum Shahzad, Dheerendra Gupta, Fabian Bock, Hongjie Wang, Haroon Shaikh, Thilo Kähne, Dirk Reinhold, Ute Bank, Ana C Zenclussen, Jana Niemz, Tina M Schnöder, Monika Brunner-Weinzierl, Thomas Fischer, Thomas Kalinski, Burkhart Schraven, Thomas Luft, Jochen Huehn, Michael Naumann, Florian H Heidel, Berend Isermann
Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4(+)FOXP3(+))...
August 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811939/abo-gene-polymorphism-and-thrombomodulin-33g-a-polymorphism-were-not-risk-factors-for-myocardial-infarction-in-javanese-men
#14
Mifetika Lukitasari, Ahmad Hamim Sadewa, Mohammad Saifur Rohman
Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism -33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism -33G>A with the incidence of acute myocardial infarction (AMI). A total of 192 subjects were enrolled in this case control study...
2017: International Journal of Vascular Medicine
https://www.readbyqxmd.com/read/28792000/-lower-extremity-varicose-veins-in-childhood-and-at-a-young-age-mechanism-of-development-and-specific-features
#15
V V Studennikova, L O Severgina, A N Dzyundzya, I A Korovin
In Russia more than 125,000 patients with various venous diseases, lower extremity varicose veins (LEVV) being predominant, were annually operated on. In recent years, there has been a trend toward younger patients with signs of LEVV. Screening studies have revealed the signs of the disease in 10-15% of high-school children. The high prevalence of LEVV as a whole and its younger onset in recent decades cause more attention to an investigation of the relationship between the development of varicose veins, in childhood and adolescence in particular, and genomic changes...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28774197/thrombotic-and-hemorrhagic-conditions-due-to-a-gain-of-function-of-coagulation-proteins-a-special-type-of-clotting-disorders
#16
Antonio Girolami, Elisabetta Cosi, Silvia Ferrari, Annamaria Lombardi, Fabrizio Fabris
Coagulation disorders can be classified into 2 types, namely, type I and type II. In the former, there is a concomitant decrease in factor activity and antigen (activity-antigen ratio is 1), whereas in the latter, there is a discrepancy between factor activity which is always low and antigen which is normal or near normal (activity-antigen ratio is <1, eg, 0.5). Recently, several gain-of-function disorders have been described. These are characterized by an increased activity with respect to the antigen level...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28771780/successful-combination-therapy-of-propranolol-and-prednisolone-for-a-case-with-congenital-kasabach-merritt-syndrome
#17
Kento Mizutani, Ai Umaoka, Kenshiro Tsuda, Masato Kakeda, Koji Habe, Keiichi Yamanaka, Megumi Suyama, Hitoshi Mizutani
A male fetus was delivered by cesarean section with a large hemangioma on his right chest and thrombocytopenia. Clinically, Kasabach-Merritt syndrome (KMS) was suspected, and immediately he was treated with daily prednisolone (PSL) 1 mg/kg and recombinant thrombomodulin without response. Additional propranolol (1-3 mg/kg per day) and increased PSL 2 mg/kg per day therapy successfully controlled his disseminated intravascular coagulation and decreased the tumor size without serious side-effects. No relapse of KMS was observed after cease of PSL and propranolol...
August 3, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28771554/increased-serum-thrombomodulin-level-is-associated-with-disease-severity-and-mortality-in-pediatric-sepsis
#18
Jainn-Jim Lin, Hsiang-Ju Hsiao, Oi-Wa Chan, Yu Wang, Shao-Hsuan Hsia, Cheng-Hsun Chiu
BACKGROUND: Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury. OBJECTIVE: The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality. METHODS: We prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children's Hospital in Taoyuan, Taiwan...
2017: PloS One
https://www.readbyqxmd.com/read/28756988/tissue-hemostasis-is-shifted-toward-thrombogenesis-in-the-psoriatic-plaques
#19
Edyta Gębska, Agnieszka Sikora-Żydek, Marek Michalski, Edyta Reichman-Warmusz, Józef Kurek, Damian Dudek, Wiktor Skowron, Jerzy Jarząb, Romuald Wojnicz
BACKGROUND: Psoriasis is a common autoimmune disease of unknown etiology. Recently, much attention has been paid to evidence that a local hypercoagulable state is an important contributing factor to the development of inflammatory skin diseases. Thus, the aim of this study was to characterize the local hemostasis in the affected skin of patients with psoriasis. METHODS: Skin biopsies of psoriatic plaques were obtained from 73 consecutive patients (48M, 25F, average age 45 years) with at least a one year history of the disease...
July 15, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28755135/macrophage-derived-hmgb1-as-a-pain-mediator-in-the-early-stage-of-acute-pancreatitis-in-mice-targeting-rage-and-cxcl12-cxcr4-axis
#20
Yuhei Irie, Maho Tsubota, Hiroyasu Ishikura, Fumiko Sekiguchi, Yuka Terada, Toshifumi Tsujiuchi, Keyue Liu, Masahiro Nishibori, Atsufumi Kawabata
Extracellular high mobility group box 1 (HMGB1) activates the receptor for advanced glycation end products (RAGE) or Toll-like receptor 4 (TLR4) and forms a heterocomplex with CXCL12 that strongly activates CXCR4, promoting inflammatory and pain signals. In the present study, we investigated the role of HMGB1 in pancreatic pain accompanying cerulein-induced acute pancreatitis in mice. Abdominal referred hyperalgesia accompanying acute pancreatitis occurred within 1 h after 6 hourly injections of cerulein. The anti-HMGB1 neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, abolished the cerulein-induced referred hyperalgesia, but not pancreatitis itself...
July 28, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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