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thrombomodulin

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https://www.readbyqxmd.com/read/28645823/recombinant-human-soluble-thrombomodulin-prevents-acute-lung-injury-in-a-rat-cardiopulmonary-bypass-model
#1
Shingo Hirao, Kenji Minakata, Hidetoshi Masumoto, Kazuhiro Yamazaki, Tadashi Ikeda, Kenji Minatoya, Ryuzo Sakata
BACKGROUND: Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate the secretion of inflammatory cytokines and the high-mobility group box 1 (HMGB1) protein, which is critical in controlling systemic inflammation and apoptosis. We investigated the protective effects of rTM on CPB-induced lung injury in a rat model. METHODS: Eighteen male Sprague-Dawley rats were divided into 3 groups: sham, control (CPB alone), and rTM (CPB + rTM)...
May 30, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28640323/lys-42-43-44-and-arg-12-of-thrombin-activable-fibrinolysis-inhibitor-comprise-a-thrombomodulin-exosite-essential-for-its-antifibrinolytic-potential
#2
Chengliang Wu, Alan R Stafford, James C Fredenburgh, Jeffrey I Weitz, Ann Gils, Paul J Declerck, Paul Y Kim
The thrombin-thrombomodulin (TM) complex activates thrombin-activable fibrinolysis inhibitor (TAFI) more efficiently than thrombin alone. The exosite on TAFI required for its TM-dependent activation by thrombin has not been identified. Based on previous work by us and others, we generated TAFI variants with one or more of residues Lys 42, Lys 43, Lys 44 and Arg 12 within the activation peptide mutated to alanine. Mutation of one, two, or three Lys residues or the Arg residue alone decreased the catalytic efficiency of TAFI activation by thrombin-TM by 2...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28628220/importance-of-endothelial-dysfunction-biomarkers-in-patients-with-crimean-congo-hemorrhagic-fever
#3
Mustafa Arslan, Gürdal Yilmaz, Ahmet Mentese, Hülya Yilmaz, S Caner Karahan, Iftihar Koksal
BACKGROUND: The pathogenesis of the Crimean-Congo hemorrhagic fever (CCHF) and the cause of the hemorrhage are not yet fully understood. However, the endothelium plays a key role in the pathogenesis. The purpose of this study was to investigate endothelial dysfunction markers [asymmetrical dimethyl arginine(ADMA), endothelin 1(ET-1), thrombomodulin(TM), von Willebrand factor(vWf) and intercellular adhesion molecule(ICAM-1)] in serum in patients with CCHF and their associations with hemorrhage...
June 19, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28619983/failure-to-replicate-thrombomodulin-genetic-variant-predictors-of-venous-thromboembolism-in-african-americans
#4
Aaron R Folsom, Nicholas S Roetker, Spencer T Kelley, Weihong Tang, Nathan Pankratz
No abstract text is available yet for this article.
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28607460/recombinant-thrombomodulin-exerts-anti-autophagic-action-in-endothelial-cells-and-provides-anti-atherosclerosis-effect-in-apolipoprotein-e-deficient-mice
#5
Po-Sheng Chen, Kuan-Chieh Wang, Ting-Hsing Chao, Hsing-Chun Chung, Shi-Ya Tseng, Chawn-Yau Luo, Guey-Yueh Shi, Hua-Lin Wu, Yi-Heng Li
Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592770/dic-an-update-on-diagnosis-and-treatment
#6
Hideo Wada, Kei Hasegawa, Maki Watanabe
Disseminated intravascular coagulation (DIC) was considered to be a fatal disease. However, it has recently been suggested that very early DIC protects the host against microthrombosis and infection localization. Therefore, early treatment of DIC may be contraindicated in patients with sepsis. These factors suggest that the diagnosis and treatment of DIC will gain further importance. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG2016), which include details regarding the management of DIC, have been recently published...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28587368/evaluation-of-the-effect-of-recombinant-thrombomodulin-on-a-lipopolysaccharide-induced-murine-sepsis-model
#7
Kazuhiro Takehara, Taisuke Murakami, Kyoko Kuwahara-Arai, Toshiaki Iba, Isao Nagaoka, Kazuhiro Sakamoto
To evaluate the effect of recombinant human thrombomodulin (rTM) on sepsis, the levels of nucleosome as well as high-mobility group box 1 (HMGB1) and cytokines in sera and peritoneal fluids were measured in a mouse model of lipopolysaccharide (LPS)-induced sepsis after administration of rTM. C57BL/6 mice were intraperitoneally injected with LPS (15 mg/kg; Escherichia coli O111:B4) with or without the intravenous administration of rTM (3 mg/kg; 30 min prior to or 2 h after LPS injection). The survival rates were evaluated and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, HMGB1 and nucleosome in sera and peritoneal fluids were analyzed by ELISA...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28579548/syndecan-1-a-quantitative-marker-for-the-endotheliopathy-of-trauma
#8
Erika Gonzalez Rodriguez, Sisse R Ostrowski, Jessica C Cardenas, Lisa A Baer, Jeffrey S Tomasek, Hanne H Henriksen, Jakob Stensballe, Bryan A Cotton, John B Holcomb, Pär I Johansson, Charles E Wade
BACKGROUND: Endothelial glycocalyx breakdown elicits syndecan-1 shedding, and traumatic endotheliopathy (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. STUDY DESIGN: Prospective observational study; trauma patients with the highest level of activation admitted during July 2011-September 2013 were eligible. We recorded demographics, injury type/severity (ISS), physiology and outcome data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs...
June 1, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28578476/lipopolysaccharide-downregulates-kruppel-like-factor-2-klf2-via-inducing-dnmt1-mediated-hypermethylation-in-endothelial-cells
#9
Zhonghai Yan, Yan Deng, Fei Jiao, Junqi Guo, Hailong Ou
KLF2 plays a protective role in antiinflammation and endothelial function, and can be regulated by promoter methylation alteration. Lipopolysaccharide (LPS) is a mediator of inflammatory responses, which causes epigenetic change of certain genes in host cells. We thus aimed to determine whether LPS could control the KLF2 expression by inducing methylation in promoter region. DNA methylation of 16 CpG sites within KLF2 promoter region was detected by bisulfite sequencing PCR. Results showed that methylation at 12 CpG sites were significantly increased in HUVECs after exposure to LPS among the total 16 sites, and the average level was increased by 57%...
June 3, 2017: Inflammation
https://www.readbyqxmd.com/read/28572981/the-application-of-anticoagulant-therapy-to-sepsis
#10
Jecko Thachil, Toshiaki Iba
Since the withdrawal of recombinant-activated protein C, the anticoagulant therapy for sepsis was taken no notice. For instance, the international sepsis guidelines did not share a space for this therapy. However, we can see the signs of change recently. The Surviving Sepsis Campaign Guidelines 2016 introduced the development of recombinant thrombomodulin, and the European Society of Intensive Care Medicine released comments on this subject. However, since small but important discrepancy was recognized between the standpoints of Japan (more aggressive) and other countries (rather conservative), we intend to discuss on this point...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28571971/biological-reproducibility-of-circulating-p-selectin-thrombopoietin-gpiib-iiia-and-thrombomodulin-over-one-year
#11
Mirja E Graf, Disorn Sookthai, Theron Johnson, Ruth Schübel, Verena Katzke, Peter Bugert, Michael Hoffmeister, Rudolf Kaaks, Tilman Kühn
BACKGROUND: Enhanced platelet activation has been implicated in several pathophysiological processes. Here, we evaluated the biological reproducibility of circulating P-Selectin, Thrombomodulin (TM), Thrombopoietin (TPO), and Glycoprotein IIb/IIIa (GPIIb/IIIa) to assess whether these analytes can be used as reliable biomarkers of platelet activation in epidemiological studies. METHODS: We measured circulating P-Selectin, TM, TPO and GPIIb/IIIa by immunoassays in two blood samples of 78 participants of the EPIC Heidelberg study (47-80years, 50% female) that were collected one year apart...
May 29, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28569919/elevated-plasma-tfpi-activity-causes-attenuated-tf-dependent-thrombin-generation-in-early-onset-preeclampsia
#12
Karl Egan, Hugh O'Connor, Barry Kevane, Fergal Malone, Aine Lennon, Amani Al Zadjali, Sharon Cooley, Cathy Monteith, Patricia Maguire, Paulina Szklanna, Seamus Allen, Naomi McCallion, Fionnuala Ní Áinle
Early onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin. Twenty-six cases of EOP were recruited over a 21-month period, out of 15,299 deliveries at the Rotunda. Blood samples were collected into sodium citrate plus corn trypsin inhibitor anticoagulated vacutainers, platelet-poor plasma was prepared, and calibrated automated thrombography was used to assess thrombin generation...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28566591/dual-therapy-with-aspirin-and-cilostazol-may-improve-platelet-aggregation-in-noncardioembolic-stroke-patients-a-pilot-study
#13
Yoichi Ohnuki, Yuko Ohnuki, Saori Kohara, Mie Shimizu, Shunya Takizawa
Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone. Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28549218/exosite-2-directed-ligands-attenuate-protein-c-activation-by-the-thrombin-thrombomodulin-complex
#14
Kai Chen, Alan R Stafford, Chengliang Wu, Calvin H Yeh, Paul Y Kim, James C Fredenburgh, Jeffrey I Weitz
Thrombin activity, inhibition, and localization are regulated by two exosites that flank the active site. Substrates, cofactors, and inhibitors bind to exosite 1 to promote active site access, whereas exosite 2 interactions hold thrombin on cells, platelets, and proteins. The exosites also serve allosteric roles, whereby ligand binding alters thrombin activity. Previously, we showed that ligands that bind exosite 2 attenuate the exosite 1-mediated interaction of thrombin with fibrin, demonstrating allosteric connection between the exosites...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28544968/clinical-usefulness-of-videocapillaroscopy-and-selected-endothelial-cell-activation-markers-in-people-with-type-1-diabetes-mellitus-complicated-by-microangiopathy
#15
Anna Kuryliszyn-Moskal, Wieslaw Zarzycki, Artur Dubicki, Diana Moskal, Bozena Kosztyła-Hojna, Anna Hryniewicz
PURPOSE: Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of our study was to compare microvascular changes examined by nailfold videocapillaroscopy (NVC) examination with serum concentrations of vascular endothelial growth factor (VEGF), soluble thrombomodulin (sTM) and endothelin-1 (ET-1) in people with Type 1 diabetes with and without microangiopathy. MATERIAL/METHODS: The study included 106 people with Type 1 diabetes and 40 healthy controls...
May 22, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28540449/epidermoid-cysts-are-a-characteristic-feature-of-intrapancreatic-but-not-of-extrapancreatic-accessory-spleens
#16
Kenichi Hirabayashi, Misuzu Yamada, Hirotaka Kono, Atsuko Hadano, Aya Kawanishi, Yumi Takanashi, Yoshiaki Kawaguchi, Toshio Nakagohri, Tetsuya Mine, Naoya Nakamura
Accessory spleens (ASs), ectopic splenic tissue at intrapancreatic and extrapancreatic sites, rarely contain epidermoid cysts. Our aim was to analyze the incidence of epidermoid cysts in ASs and perform an immunohistochemical analysis of its epithelial lining. We included in the study 148 ASs from 135 patients, for which pathological data were available. Eleven were intrapancreatic ASs (IPASs) and 137 were extrapancreatic ASs (EPASs). Six of the eleven (55%) IPASs contained epidermoid cysts, but they were not detected in EPASs...
May 24, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28538400/carbon-monoxide-releasing-molecule-2-suppresses-thrombomodulin-and-endothelial-protein-c-receptor-expression-of-human-umbilical-vein-endothelial-cells-induced-by-lipopolysaccharide-in-vitro
#17
Xianglin Meng, Dongsheng Fei, Mingming Liu, Songlin Yang, Ning Song, Lei Jiang, Kai Kang, Chuanchuan Nan, Yunpeng Luo, Shangha Pan, Mingyan Zhao
OBJECTIVE: The aim of this study was to observe the counter-effect of carbon monoxide-releasing molecule-2 (CORM-2) on lipopolysaccharide (LPS)-suppressed thrombomodulin (TM) and endothelial protein C receptor (EPCR) expressions from human umbilical vein endothelial cell (HUVEC), and to reveal its mechanisms. METHODS: HUVECs were divided into 5 treatment groups, wherein reagents were added simultaneously. TM and EPCR proteins of the cells and the culture medium levels of soluble TM, soluble EPCR, and matrix metalloproteinase-2 (MMP-2) were detected after administration, whereas mRNA levels of TM and EPCR, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity among groups, were also evaluated...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28525804/recombinant-adeno-associated-virus-vector-carrying-the-thrombomodulin-lectin-like-domain-for-the-treatment-of-abdominal-aortic-aneurysm
#18
Chao-Han Lai, Kuan-Chieh Wang, Cheng-Hsiang Kuo, Fang-Tzu Lee, Tsung-Lin Cheng, Bi-Ing Chang, Yu-Jen Yang, Guey-Yueh Shi, Hua-Lin Wu
BACKGROUND AND AIMS: Thrombomodulin (TM), through its lectin-like domain (TMD1), sequesters proinflammatory high-mobility group box 1 (HMGB1) to prevent it from engaging the receptor for advanced glycation end product (RAGE) that sustains inflammation and tissue damage. Our previous study demonstrated that short-term treatment with recombinant TM containing all the extracellular domains (i.e., rTMD123) inhibits HMGB1-RAGE signaling and confers protection against CaCl2-induced AAA formation...
March 18, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28505627/endothelial-damage-signals-refractory-acute-kidney-injury-in-critically-ill-patients
#19
Theis S Itenov, Jens-Ulrik Jensen, Sisse R Ostrowski, Pär I Johansson, Katrin M Thormar, Jens D Lundgren, Morten H Bestle
Critically ill patients with acute kidney injury (AKI) are heterogeneous on pathophysiology and prognosis. The role of endothelial damage in the pathogenesis of refractory AKI has not been clarified. The aim was to determine if biomarkers of endothelial damage, independently of the inflammatory insult on the kidney, can predict recovery of acute kidney injury. METHODS: From the "Procalcitonin And Survival Study" multicenter intensive care unit cohort, followed for 28 days after admission, we included patients without chronic kidney disease, who survived >24 h after admission and with plasma samples at admission available for biomarker analysis...
June 2017: Shock
https://www.readbyqxmd.com/read/28505525/thrombin-generation-and-intracranial-atherosclerotic-disease-in-patients-with-a-transient-ischaemic-attack
#20
Elisabetta Favaretto, Michelangelo Sartori, Cristina Legnani, Francesca Rondelli, Michela Cini, Maria Guarino, Benilde Cosmi
BACKGROUND: Intracranial atherosclerotic disease (ICAD) is responsible for at least 10% of transient ischaemic attacks (TIA). Thrombin generation has been shown to be associated with several atherosclerotic conditions and may be relevant in the pathogenesis of TIA from ICAD. OBJECTIVE: To evaluate the association between thrombin generation and ICAD in patients with TIA. MATERIALS AND METHODS: Consecutive patients with confirmed diagnosis of TIA by vascular neurologist were enrolled...
May 9, 2017: Thrombosis Research
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