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Brice Nativel, Audrey Figuester, Jessica Andries, Cynthia Planesse, Joël Couprie, Philippe Gasque, Wildriss Viranaicken, Thomas Iwema
CD93 belongs to the group XIV C-type lectin like domain (CTLD) and is closely related to thrombomodulin (CD141). Although CD93 is known to be involved in the regulation of cell adhesion and phagocytosis, its role in innate immunity remains to be fully investigated. Critically, published data about CD141 suggest that CD93 CTLD could be involved in the control of inflammation. In order to address further functional and structural analyses, we expressed human CD93 CTLD with several disulfide bonds in an E. coli expression system...
October 12, 2016: Journal of Immunological Methods
Masanobu Takeuchi, Reo Tanoshima, Naoyuki Miyagawa, Takeo Sarashina, Hiromi Kato, Ryosuke Kajiwara, Shinya Ito, Hiroaki Goto
BACKGROUND: Thrombomodulin alfa (TM-α) is a new class of anticoagulant drug for patients with disseminated intravascular coagulation (DIC). This study aimed to determine the pharmacokinetics of TM-α and determine the optimal dose in pediatric patients with hematological malignancy and DIC. PROCEDURE: Pediatric patients with hematological malignancy and DIC were administered TM-α at a dose of 0.06 mg/kg (380 U/kg) over 30 min every 24 hr. Blood samples were taken at steady state before the start, immediately after the end, and 24 hr after the start of the sixth administration...
October 12, 2016: Pediatric Blood & Cancer
Ammar W Ashor, Shakir Chowdhury, Clio Oggioni, Othman Qadir, Kirsten Brandt, Abbas Ishaq, John C Mathers, Gabriele Saretzki, Mario Siervo
BACKGROUND: Aging and obesity are associated with raised oxidative stress and a reduction of nitric oxide (NO) bioavailability, with subsequent decline in insulin sensitivity and endothelial function. Inorganic nitrate is converted into NO via a 2-step reduction process and may be an effective nutritional intervention to modify vascular and metabolic functions. OBJECTIVES: This study tested whether inorganic nitrate supplementation improved glucose disposal and attenuated the acute effects of hyperglycemia on oxidative stress, inflammation, and vascular function in young and old obese participants...
October 12, 2016: Journal of Nutrition
Per Lehnert, Pär I Johansson, Sisse R Ostrowski, Christian H Møller, Lia E Bang, Peter Skov Olsen, Jørn Carlsen
Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones)...
October 11, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Maria Renata Sales Nogueira, Ana Carla Pereira Latini, Maria Esther Salles Nogueira
Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls...
October 3, 2016: Memórias do Instituto Oswaldo Cruz
Shunsuke Tawara, Takumi Sakai, Osamu Matsuzaki
BACKGROUND: Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro...
September 17, 2016: Thrombosis Research
Daiji Takeuchi, Kei Inai, Tokuko Shinohara, Toshio Nakanishi, In-Sam Park
BACKGROUND: Coagulation abnormality is associated with a high incidence of intracardiac thrombus (ICT) and systemic thromboembolism in Fontan patients. The biomarker for detecting ICT is currently unknown. METHODS: We retrospectively investigated the underlying coagulation abnormality and useful biomarkers to screen for ICT in adult Fontan patients. We measured various biomarkers of blood coagulation, fibrinolysis, and platelet activity in 122 Fontan patients (Fontan group: median age [P25-P75]: 27 [20-34] years) and compared them to those in 50 patients with atrial septal defect (ASD group: 31 [24-40] years)...
September 12, 2016: International Journal of Cardiology
T Ikezoe, J Yang, C Nishioka, K Umezawa, A Yokoyama
Recombinant human soluble thrombomodulin (rTM) counteracted capillary leakage and alleviated edema in individuals with sinusoidal obstruction syndrome and engraftment syndrome after hematopoietic stem cell transplantation. We previously showed that rTM increased levels of antiapoptotic protein Mcl-1 and protected endothelial cells from calcineurin inhibitor cyclosporine A (CsA)-induced apoptosis. However, the molecular mechanisms by which rTM enhances barrier function in vascular endothelial cells remain unknown...
September 19, 2016: Bone Marrow Transplantation
Toshiaki Iba, Marcello Di Nisio, Jecko Thachil, Hideo Wada, Hidesaku Asakura, Koichi Sato, Naoya Kitamura, Daizoh Saitoh
BACKGROUND: With advances in the treatment of sepsis, the systemic inflammatory response syndrome (SIRS) has been losing its prognostic power. Since the SIRS category is no longer used for the diagnosis of sepsis, the disseminated intravascular coagulation (DIC) diagnostic criteria released by Japanese Association for Acute Medicine (JAAM) should be modified. Thus, the purpose of this study was to examine the appropriateness of replacing the SIRS score with antithrombin activity in JAAM-DIC diagnostic criteria...
2016: Critical Care: the Official Journal of the Critical Care Forum
Hiroyuki Ohbe, Daisuke Kudo, Satoshi Yamanouchi, Shigeki Kushimoto
PURPOSE: The purpose of this study is to investigate the association between a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and neurologic outcome in patients with resuscitation of out-of-hospital cardiac arrest (R-OHCA). MATERIALS AND METHODS: A prospective observational study of adult patients with R-OHCA was conducted. Plasma activity of ADAMTS13 and inflammatory markers, an immunologic marker, and a marker of endothelial damage were measured on admission and day 2...
August 13, 2016: Journal of Critical Care
Laurence Rozen, Denis Noubouossie, Laurence Dedeken, Sophie Huybrechts, Phu Quoc Lê, Alina Ferster, Anne Demulder
BACKGROUND: Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events. OBJECTIVE: Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy. PROCEDURE: Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin...
September 8, 2016: Pediatric Blood & Cancer
Yuki Takagi, Moe Murata, Toshihiro Kozuka, Yukiko Nakata, Ryo Hasebe, Shogo Tamura, Akira Takagi, Tadashi Matsushita, Hidehiko Saito, Tetsuhito Kojima
Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions...
September 8, 2016: Thrombosis and Haemostasis
Yun-Yan Hsu, Guey-Yueh Shi, Kuan-Chieh Wang, Chih-Yuan Ma, Tsung-Lin Cheng, Hua-Lin Wu
Angiogenesis promotes tumor growth and metastasis. Cell adhesion molecules interact with the extracellular matrix (ECM) and increase cell adhesion and migration during angiogenesis. Thrombomodulin (TM) is a cell surface transmembrane glycoprotein expressed in endothelial cells. However, the function and significance of TM in cell-matrix interactions and angiogenesis remain unclear. Here, we first demonstrated that recombinant lectin-like domain of TM interacts with an ECM protein, fibronectin, and identified the N-terminal 70-kDa domain of fibronectin as the TM-binding site...
September 2, 2016: Oncotarget
Alisha McLoughlin, Keith D Rochfort, Cormac J McDonnell, Steven W Kerrigan, Philip M Cummins
Blood-brain barrier (BBB) disruption constitutes a hallmark event during pathogen-mediated neurological disorders such as bacterial meningitis. As a prevalent opportunistic pathogen, Staphylococcus aureus (SA) is of particular interest in this context, although our fundamental understanding of how SA disrupts the BBB is very limited. This paper employs in vitro infection models to address this. Human brain microvascular endothelial cells (HBMvECs) were infected with formaldehyde-fixed (multiplicity of infection [MOI] 0-250, 0-48 hr) and live (MOI 0-100, 0-3 hr) SA cultures...
September 6, 2016: Cellular Microbiology
Juliane Wolter, Lorenz Schild, Fabian Bock, Andrea Hellwig, Ihsan Gadi, Moh D Mohanad Al-Dabet, Satish Ranjan, Raik Rönicke, Peter P Nawroth, Karl-Uwe Petersen, Christian Mawrin, Khurrum Shahzad, Berend Isermann
BACKGROUND: Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases, e.g. in multiple sclerosis (MS) and experimental autoimmune encephalitis (EAE). Surprisingly, approaches to increase aPC plasma levels as well as antibody mediated inhibition of PC/aPC ameliorated EAE in mice. Hence, the role of aPC generation in demyelinating diseases and potential mechanisms involved remain controversial. Furthermore, it is not known whether loss of aPC has pathological consequences at baseline, e...
September 3, 2016: Journal of Thrombosis and Haemostasis: JTH
B Ke
No abstract text is available yet for this article.
September 1, 2016: American Journal of Transplantation
Cheng Hock Toh, Yasir Alhamdi, Simon T Abrams
Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface...
November 2016: Annals of Laboratory Medicine
Akinori Ochi, Taro Adachi, Koichiro Inokuchi, Ko Ogawa, Yuya Nakamura, Yuta Chiba, Shiro Kawasaki, Yoshimi Onishi, Yoshimasa Onuma, Yumi Munetsugu, Hiroyuki Ito, Tatsuya Onuki, Yoshino Minoura, Norikazu Watanabe, Mitsuharu Kawamura, Taku Asano, Youichi Kobayashi
BACKGROUND: Although clinical trials demonstrate that the elderly with atrial fibrillation have risks of thrombosis and bleeding, the relationship between aging and coagulation fibrinolytic system in "real-world" cardiology outpatients is uncertain. METHODS AND RESULTS: We retrospectively evaluated 773 patients (mean age: 58 years; 52% men; Asian ethnicity). To thoroughly investigate markers of coagulation and fibrinolysis, we simultaneously measured levels of D-dimer, prothrombin-fragment1+2 (F1+2), plasmin-α2 plasmin inhibitor complex (PIC), and thrombomodulin (TM)...
September 23, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
N Y Maeda, M M Clavé, S P Bydlowski, A A Lopes
INTRODUCTION: Advanced pulmonary arterial hypertension (PAH) in patients with congenital cardiac communications and right-to-left shunting (Eisenmenger syndrome - PAH-ES) is associated with hypoxemia and decreased circulating levels of thrombomodulin (TM), probably reflecting decreased endothelial TM production. The combination of these two factors has been shown to induce fibrin deposition, with increased risk of thrombosis, a well known complication in this syndrome. PATIENTS AND METHODS: We tested the hypothesis that vasodilator therapy with the phosphodiesterase-5 inhibitor tadalafil, an approved drug for management of PAH could improve endothelial dysfunction markers, in particular plasma TM, in addition to improving the physical capacity (expected effect of pulmonary vasodilatation) in PAH-ES patients...
October 2016: Thrombosis Research
Tom Plug, Joost C M Meijers
BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a proenzyme that, once activated, attenuates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin. TAFI can be activated by thrombin or plasmin via a cleavage at Arg92 that removes the activation peptide from the enzyme, TAFIa. Thrombomodulin enhances thrombin-mediated TAFI activation and glycosaminoglycans enhance plasmin-mediated TAFI activation. The aim of this study was to investigate whether there are other anionic molecules that function as a cofactor for thrombin- or plasmin-mediated TAFI activation...
October 2016: Thrombosis Research
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