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https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#1
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28176226/evaluation-of-the-safety-and-efficacy-of-recombinant-soluble-thrombomodulin-for-patients-with-disseminated-intravascular-coagulation-associated-with-acute-leukemia-multicenter-prospective-study-by-the-tohoku-hematology-forum
#2
Hisayuki Yokoyama, Naoto Takahashi, Yuna Katsuoka, Mitsue Inomata, Toshihiro Ito, Kuniaki Meguro, Yoshihiro Kameoka, Riko Tsumanuma, Kazunori Murai, Hideyoshi Noji, Kenichi Ishizawa, Shigeki Ito, Yasushi Onishi, Hideo Harigae
It has been suggested that use of recombinant soluble thrombomodulin (rTM) is superior to conventional drugs in treatment of disseminated intravascular coagulation (DIC) complicating acute leukemia. However, its safety and efficacy have not been fully examined in prospective studies. Here, we performed a multicenter prospective study to examine outcomes of rTM treatment for DIC in patients with acute leukemia. Of 33 patients registered in this study, 13 had acute myeloid leukemia (AML), three had acute lymphoblastic leukemia (ALL), and 17 had acute promyelocytic leukemia (APL)...
February 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28167153/the-fifth-egf-like-region-of-thrombomodulin-alleviates-murine-graft-versus-host-disease-in-a-g-protein-coupled-receptor-15-dependent-manner
#3
Bin Pan, Xiangmin Wang, Shinsuke Kojima, Chie Nishioka, Akihito Yokoyama, Goichi Honda, Kailin Xu, Takayuki Ikezoe
Thrombomodulin (TM) exerts anti-inflammatory functions. We previously found that recombinant human soluble thrombomodulin (rTM) alleviated murine graft-versus-host disease (GVHD). Nevertheless, it is unclear how TM mediates its anti-inflammatory functions in GVHD. Here, we identified G-protein coupled receptor 15 (GPR15) expressed on T cells as a receptor/sensor of TM. The fifth region of epidermal growth factor(EGF)-like domain of TM (TME5) bound GPR15 in vitro. TME5 prolonged survival of mice undergoing aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
February 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28150854/imaging-analyses-of-coagulation-dependent-initiation-of-fibrinolysis-on-activated-platelets-and-its-modification-by-thrombin-activatable-fibrinolysis-inhibitor
#4
Tomasz Brzoska, Yuko Suzuki, Hideto Sano, Seiichirou Suzuki, Martyna Tomczyk, Hiroki Tanaka, Tetsumei Urano
Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the center of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28148301/protective-effects-of-molecular-hydrogen-on-steroid-induced-osteonecrosis-in-rabbits-via-reducing-oxidative-stress-and-apoptosis
#5
Jia Li, Zhaogang Ge, Lihong Fan, Kunzheng Wang
BACKGROUND: The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model. METHODS: Sixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28129465/evaluation-of-coagulation-during-treatment-with-directly-acting-antivirals-in-patients-with-hepatitis-c-virus-related-cirrhosis
#6
Armando Tripodi, Roberta D'Ambrosio, Lidia Padovan, Giulia Tosetti, Alessio Aghemo, Massimo Primignani, Veena Chantarangkul, Flora Peyvandi, Massimo Colombo
BACKGROUND & AIMS: The effect of direct-acting-antivirals (DAA) on coagulation of hepatitis-C-virus (HCV)-related cirrhosis is unknown. METHODS: We investigated 28 patients on DAA treatment and performed prothrombin-time, thrombin-generation with and without thrombomodulin, whole-blood thromboelastometry, as well as the individual procoagulants (II, VIII, XIII, von-Willebrand) and anticoagulants, antithrombin and protein-C. RESULTS: Patients had undetectable HCV-RNA at the end-of- treatment and at 12-weeks after end-of-treatment (sustained-virological-response)...
January 27, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28124276/activated-thrombin-activatable-fibrinolysis-inhibitor-attenuates-the-angiogenic-potential-of-endothelial-cells-potential-relevance-to-the-breast-tumour-microenvironment
#7
Zainab A Bazzi, Jennifer Balun, Dora Cavallo-Medved, Lisa A Porter, Michael B Boffa
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a basic carboxypeptidase zymogen present in blood plasma. Proteolytic activation of TAFI by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin, or plasmin results in an enzyme (TAFIa) that removes carboxyl-terminal lysine residues from protein and peptide substrates, including cell-surface plasminogen receptors. TAFIa is therefore capable of inhibiting plasminogen activation in the pericellular milieu. Since plasminogen activation has been linked to angiogenesis, TAFIa could therefore have anti-angiogenic properties, and indeed TAFIa has been shown to inhibit endothelial tube formation in a fibrin matrix...
January 25, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28122514/indoxyl-sulfate-the-uremic-toxin-linking-hemostatic-system-disturbances-with-the-prevalence-of-cardiovascular-disease-in-patients-with-chronic-kidney-disease
#8
Tomasz W Kamiński, Krystyna Pawlak, Małgorzata Karbowska, Michał Myśliwiec, Dariusz Pawlak
BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study...
January 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28121350/thrombomodulin-regulates-doxorubicin-sensitivity-through-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer
#9
Y Yang, B-J Cheng, S Lu
OBJECTIVE: Lung cancer has remained the highest about cancer-related mortality and drug resistance is involved in the recurrence of the disease. Thrombomodulin (TM) is down-regulated in several malignant tumors, but its role in drug resistance has not been elucidated in lung cancer. We aimed to investigate the role of TM in drug resistance to lung cancer. MATERIALS AND METHODS: The mRNA and protein expression of TM were determined by real-time PCR and Western blot, respectively...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28114372/bubble-induced-endothelial-microparticles-promote-endothelial-dysfunction
#10
Xuhua Yu, Jiajun Xu, Guoyang Huang, Kun Zhang, Long Qing, Wenwu Liu, Weigang Xu
Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28109962/endothelial-permeability-and-hemostasis-in-septic-shock-results-from-the-process-trial
#11
Peter Hou, Michael Filbin, Henry Wang, Long Ngo, David T Huang, William C Aird, Donald M Yealy, Derek C Angus, John A Kellum, Nathan I Shapiro
BACKGROUND: We studied patients from the Protocolized Care in Early Septic Shock (ProCESS) trial to determine: the effects of alternative resuscitation strategies on circulating markers of endothelial cell permeability and hemostasis, and; the association between biomarkers and mortality. METHODS: Prospective study of biomarkers of endothelial cell permeability (vegf, sflt-1, ang-2) and hemostasis (vwf, thrombomodulin, tpa) in 605 of the 1341 ProCESS participants in a derivation cohort and 305 in validation...
January 18, 2017: Chest
https://www.readbyqxmd.com/read/28099190/coagulation-imbalance-and-neurocognitive-functioning-in-older-hiv-adults-on-suppressive-antiretroviral-therapy
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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