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thrombomodulin

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https://www.readbyqxmd.com/read/28099190/coagulation-imbalance-and-neurocognitive-functioning-in-older-hiv-adults-on-suppressive-antiretroviral-therapy
#1
Jessica L Montoya, Jennifer Iudicello, Hannah A Oppenheim, Pariya L Fazeli, Michael Potter, Qing Ma, Paul J Mills, Ronald J Ellis, Igor Grant, Scott L Letendre, David J Moore
OBJECTIVES: To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. DESIGN: Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. METHODS: Participants completed standardized neurobehavioral and neuromedical assessments...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28094003/recombinant-thrombomodulin-suppresses-tumor-growth-of-pancreatic-cancer-by-blocking-thrombin-induced-par1-and-nf-%C3%AE%C2%BAb-activation
#2
Yoshihiro Shirai, Tadashi Uwagawa, Hiroaki Shiba, Yohta Shimada, Takashi Horiuchi, Nobuhiro Saito, Kenei Furukawa, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Thrombomodulin, an anticoagulant that inhibits thrombin-induced growth factor promotion, also has an anti-inflammatory effect. Furthermore, thrombomodulin inhibits nuclear factor-kappa B activation, which plays a crucial role in cancer progression. We assessed the antitumor activity of recombinant thrombomodulin for pancreatic cancer. METHODS: A xenograft orthotopic model was established in mice by implantation of human pancreatic cancer cells. The animals were treated with intraperitoneal injection of recombinant thrombomodulin 5 times a week for 4 weeks...
January 13, 2017: Surgery
https://www.readbyqxmd.com/read/28078348/the-fifth-epidermal-growth-factor-like-region-of-thrombomodulin-alleviates-lps-induced-sepsis-through-interacting-with-g-protein-coupled-receptor-15
#3
Bin Pan, Xiangmin Wang, Shinsuke Kojima, Chie Nishioka, Akihito Yokoyama, Goichi Honda, Kailin Xu, Takayuki Ikezoe
Thrombomodulin (TM) exerts cytoprotection via the fifth region of epidermal growth factor (EGF)-like domain of TM (TME5) by interacting with G-protein coupled receptor 15 (GPR15) expressed on cell surface of vascular endothelial cells. TM is also implied to mediate anti-inflammatory functions by unknown mechanism. By applying a lipopolysaccharide (LPS)-induced murine sepsis model, we assessed the role of TME5 in septic inflammation and coagulation. We found that TME5 treatment protected mice in association with ameliorating inflammation and coagulopathy in LPS-induced sepsis...
January 12, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28049360/identification-of-genetic-aberrations-in-thrombomodulin-gene-in-patients-with-recurrent-venous-thromboembolism
#4
Abrar Ahmad, Kristina Sundquist, Bengt Zöller, Peter J Svensson, Jan Sundquist, Ashfaque A Memon
Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation of anticoagulant protein C pathway. Genetic aberrations in THBD have been studied in arterial and venous thrombosis. However, genetic changes in THBD and their role in the risk assessment of recurrent venous thromboembolism (VTE) are not well understood. The aim of the present study was to identify the genetic aberrations in THBD and their association with the risk of VTE recurrence in a prospective population-based study. We sequenced the entire THBD gene, first in selected patients with VTE (n = 95) by Sanger sequencing and later validated those polymorphisms with minor allele frequency (MAF) ≥5% in the whole study population (n = 1465 with the follow-up period of 1998-2008) by Taqman polymerase chain reaction...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28039291/can-recombinant-human-thrombomodulin-increase-survival-among-patients-with-severe-septic-induced-disseminated-intravascular-coagulation-a-single-centre-open-label-randomised-controlled-trial
#5
Akiyoshi Hagiwara, Noriko Tanaka, Tatsuki Uemura, Wataru Matsuda, Akio Kimura
OBJECTIVE: To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC). DESIGN: Single-centre, open-label, randomised controlled trial. SETTING: Single tertiary hospital. PARTICIPANT: 92 patients with severe septic-induced DIC. INTERVENTIONS: Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC...
December 30, 2016: BMJ Open
https://www.readbyqxmd.com/read/28002748/a-mathematical-model-of-venous-thrombosis-initiation
#6
Priscilla Elizondo, Aaron L Fogelson
We present a mathematical model for the initiation of venous thrombosis (VT) due to slow flow and the consequent activation of the endothelial cells (ECs) lining the vein, in the absence of overt mechanical disruption of the EC layer. It includes all reactions of the tissue factor (TF) pathway of coagulation through fibrin formation, incorporates the accumulation of blood cells on activated ECs, accounts for the flow-mediated delivery and removal of coagulation proteins and blood cells from the locus of the reactions, and accounts for the activity of major inhibitors including heparan-sulfate-accelerated antithrombin and activated protein C...
December 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27976836/soluble-thrombomodulin-in-bronchoalveolar-lavage-fluid-is-an-independent-predictor-of-severe-drug-induced-lung-injury
#7
Atsushi Suzuki, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masahiko Ando, Naohiro Watanabe, Tomoki Kimura, Kensuke Kataoka, Toshiki Yokoyama, Koji Sakamoto, Yoshinori Hasegawa
BACKGROUND AND OBJECTIVE: Drug-induced lung injury (DLI) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome (ARDS). Previous studies have reported that circulating levels of soluble thrombomodulin (TM) reflect endothelial injuries, which play key roles in the development of ARDS. We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe DLI. The primary aim of this study was to examine the associations between soluble TM and disease severity in DLI patients...
December 15, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27975099/paradoxical-bleeding-and-thrombotic-episodes-of-dysprothrombinaemia-due-to-a-homozygous-arg382his-mutation
#8
Qiulan Ding, Likui Yang, Xiaoqing Zhao, Wenman Wu, Xuefeng Wang, Alireza R Rezaie
We have characterised the pathogenic basis of dysprothrombinaemia in a patient exhibiting paradoxical bleeding and thrombotic defects during pregnancy and postpartum. Genetic analysis revealed that the proband is homozygous for the prothrombin Arg382His mutation, possessing only ~1 % clotting activity. The proband experienced severe bleeding episodes during her pregnancy, which required treatment with prothrombin complex concentrates, and then pulmonary embolism and deep-vein thrombosis at 28 days postpartum, which required treatment with LMWH and fresh frozen plasma...
December 15, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27931131/baseline-and-treatment-related-changes-in-thrombin-generation-in-patients-with-multiple-myeloma
#9
Ing S Tiong, Susan E Rodgers, Cindy H S Lee, Simon J McRae
The prothrombotic risk in multiple myeloma (MM) could be potentially assessed by thrombin generation (TG) assays. TG was performed using Calibrated Automated Thrombography with 5 and 1 pM tissue factor. We compared baseline TG among 24 MM patients, 19 MGUS, and 50 healthy controls, and assessed change in TG in MM patients during the initial treatment period at 1, 2, and 3 months. MM subjects demonstrated increased FVIII and VWF:Ag levels pretreatment, and a prothrombotic TG phenotype with increased velocity index, reduced lag time and time-to-peak, and increased resistance to thrombomodulin inhibition...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27928886/f376a-m388a-solulin-a-new-promising-antifibrinolytic-for-severe-haemophilia-a
#10
J Parcq, K U Petersen, A Borel-Derlon, P Gautier, M Ebel, D Vivien, Y Repessé
INTRODUCTION: Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics...
December 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27926661/the-effect-of-intraoperative-and-6-h-postoperative-intravenous-administration-of-low-dose-prostacyclin-on-the-endothelium-hemostasis-and-hemodynamics-in-patients-undergoing-a-pancreaticoduodenoctemy-a-randomized-controlled-pilot-study
#11
Pär I Johansson, Christian R Mortensen, Tatiana Nielsen, Carsten Tollund, Jakob Stensballe, Carsten P Hansen, Hans J Frederiksen, Sisse R Ostrowski
BACKGROUND: Capillary leakage, secondary to endothelial breakdown, is common in patients undergoing major surgical procedures with extensive tissue injury and this is associated with increased morbidity and mortality. Prostacyclin has been ascribed cytoprotective properties together with its vasodilatory and antiplatelet effects. The present pilot study investigated the safety and endothelial protective effects of low-dose prostacyclin infusion. PATIENTS AND METHODS: A randomized placebo-controlled pilot study evaluating the effect of prostacyclin (iloprost) infusion (1...
December 6, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27925234/puerarin-offsets-the-anticoagulation-effect-of-warfarin-in-rats-by-inducing-rcyps-upregulating-vitamin-k-epoxide-reductase-and-inhibiting-thrombomodulin
#12
Beikang Ge, Zhen Zhang, Teddy Taining Lam, Zhong Zuo
PURPOSE: The current study was conducted to investigate the potential pharmacokinetic and pharmacodynamic interactions between warfarin and puerarin which is the most abundant component in Pueraria lobata (Gegen). In vivo and ex vivo rat models were used to reveal the underlying mechanisms of such interactions. METHODS: Apart from one control group, five groups of Sprague-Dawley rats were treated with warfarin, oral puerarin, oral puerarin with warfarin, intravenous puerarin, intravenous puerarin with warfarin...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27910925/thrombomodulin-regulates-monocye-differentiation-via-pkc%C3%AE-and-erk1-2-pathway-in-vitro-and-in-atherosclerotic-artery
#13
Chien-Sung Tsai, Yi-Wen Lin, Chun-Yao Huang, Chun-Min Shih, Yi-Ting Tsai, Nai-Wen Tsao, Chin-Sheng Lin, Chun-Che Shih, Hellen Jeng, Feng-Yen Lin
Thrombomodulin (TM) modulates the activation of protein C and coagulation. Additionally, TM regulates monocyte migration and inflammation. However, its role on monocyte differentiation is still unknown. We investigated the effects of TM on monocyte differentiation. First, we found that TM was increased when THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA). Overexpression of TM enhanced the macrophage markers, CD14 and CD68 expression in PMA-induced THP-1. TM siRNA depressed the PMA-induced increase of p21(Cip1/WAF1) via ERK1/2-NF-kB p65 signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904864/nephrotic-range-proteinuria-and-peripheral-edema-in-a-child-not-only-idiopathic-nephrotic-syndrome
#14
Valentina Dolcemascolo, Marina Vivarelli, Manuela Colucci, Francesca Diomedi-Camassei, Rossella Piras, Marta Alberti, Francesco Emma
Hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels. Although the most common cause of HUS in children is Shiga toxin-producing Escherichia coli, atypical forms in which Shiga toxin is not the trigger may occur. Research over the last few years has shown that complement dysregulation secondary to mutations of genes coding for proteins involved in the regulation of the alternative pathway of complement account for most forms of atypical HUS (aHUS)...
September 2016: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/27876311/circulating-biomarkers-in-cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-patients
#15
Francesca Pescini, Ida Donnini, Francesca Cesari, Serena Nannucci, Raffaella Valenti, Valentina Rinnoci, Anna Poggesi, Anna Maria Gori, Betti Giusti, Angela Rogolino, Alessandra Carluccio, Silvia Bianchi, Maria Teresa Dotti, Antonio Federico, Maurizio Balestrino, Enrico Adriano, Rosanna Abbate, Domenico Inzitari, Leonardo Pantoni
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease...
November 18, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27871277/pulmonary-endothelial-activation-caused-by-extracellular-histones-contributes-to-neutrophil-activation-in-acute-respiratory-distress-syndrome
#16
Yanlin Zhang, Li Guan, Jie Yu, Zanmei Zhao, Lijun Mao, Shuqiang Li, Jinyuan Zhao
BACKGROUND: During the acute respiratory distress syndrome (ARDS), neutrophils play a central role in the pathogenesis, and their activation requires interaction with the endothelium. Extracellular histones have been recognized as pivotal inflammatory mediators. This study was to investigate the role of pulmonary endothelial activation during the extracellular histone-induced inflammatory response in ARDS. METHODS: ARDS was induced in male C57BL/6 mice by intravenous injection with lipopolysaccharide (LPS) or exogenous histones...
November 21, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27869747/the-vitamin-e-analog-gamma-tocotrienol-gt3-and-statins-synergistically-up-regulate-endothelial-thrombomodulin-tm
#17
Rupak Pathak, Sanchita P Ghosh, Daohong Zhou, Martin Hauer-Jensen
Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) and strongly induce endothelial thrombomodulin (TM); which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3) also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27865966/febuxostat-attenuates-paroxysmal-atrial-fibrillation-induced-regional-endothelial-dysfunction
#18
YanGuang Li, FuKun Chen, Long Deng, Kun Lin, Xiangmin Shi, Shan Zhaoliang, YuTang Wang
BACKGROUND: Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear. OBJECTIVE: We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO). MATERIALS AND METHODS: Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups...
January 2017: Thrombosis Research
https://www.readbyqxmd.com/read/27861629/the-relationship-between-endothelial-dysfunction-and-endothelial-cell-markers-in-peripheral-arterial-disease
#19
Kimihiro Igari, Toshifumi Kudo, Takahiro Toyofuku, Yoshinori Inoue
INTRODUCTION: The endothelial function plays key roles in both promoting and protecting against atherosclerotic disease. Several methods, including peripheral arterial tonometry (PAT), have been reported to be useful for investigating endothelial dysfunction. Furthermore, the level of thrombomodulin (TM) is assumed to reflect the endothelial dysfunction. In the present study, we investigated endothelial dysfunction in patients with peripheral arterial disease (PAD) by measuring their TM levels, and evaluated the correlation between TM and various parameters...
2016: PloS One
https://www.readbyqxmd.com/read/27850308/669-combined-therapy-gas-gangrene-antitoxin-and-recombinant-thrombomodulin-for-clostridium-perfringens
#20
Toru Hifumi, Yasuhiro Kuroda, Kenya Kawakita
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
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