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https://www.readbyqxmd.com/read/28098353/the-role-of-various-peroxisome-proliferator-activated-receptors-and-their-ligands-in-clinical-practice
#1
REVIEW
Giuseppe Derosa, Amirhossein Sahebkar, Pamela Maffioli
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in several physiological processes including modulation of cellular differentiation, development, metabolism of carbohydrates, lipids, proteins, and tumorigenesis. The aim of this review is to examine how different PPAR ligands act, and discuss their use in clinical practice. PPAR ligands have a lot of effects and applications in clinical practice. Some PPAR ligands such as fibrates (PPAR-α ligands) are currently used for the treatment of dyslipidemia, while pioglitazone and rosiglitazone (PPAR-γ ligands) are anti-diabetic and insulin-sensitizing agents...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#2
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28091816/pediatric-cerebral-sinovenous-thrombosis-following-cranial-surgery
#3
Dmitriy Petrov, Michael Y Uohara, Rebecca Ichord, Zarina Ali, Laura Jastrzab, Shih-Shan Lang, Lori Billinghurst
PURPOSE: Pediatric cerebral sinovenous thrombosis (CSVT) is an important, though less common subtype of pediatric stroke. It has been linked to several risk factors, including cranial procedures, with few studies highlighting this relationship. The aim of this study was to characterize the diagnosis and treatment of CSVT after cranial surgery. METHODS: An institutional pediatric stroke research database was used to identify all CSVT cases diagnosed within 30 days of cranial surgery from November 2004 to December 2014...
January 14, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28091396/anti-angiogenic-activity-and-antitumor-efficacy-of-amphiphilic-twin-drug-from-ursolic-acid-and-low-molecular-weight-heparin
#4
Wenming Cheng, Fatima Zohra Dahmani, Juan Zhang, Hui Xiong, Yuanyuan Wu, Lifang Yin, Jianping Zhou, Jing Yao
Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH...
January 16, 2017: Nanotechnology
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
#5
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/28076631/targeting-stroke-risk-and-improving-outcomes-in-patients-with-atrial-fibrillation-in-latin-america
#6
Bruce Stambler, Fernando Scazzuso
CONTEXT AND OBJECTIVE: To examine stroke risk factors, including atrial fibrillation, management and prevention, and stroke outcomes across Latin America. DESIGN AND SETTING: Narrative review conducted at Piedmont Heart Institute, United States. METHODS: The PubMed, Embase and Cochrane databases were searched for stroke AND "Latin America" AND epidemiology (between January 2009 and March 2015). Further studies in the SciELO, World Health Organization and Pan-American Health Organization databases were used to address specific points...
November 2016: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28074788/comparison-of-two-doses-of-heparin-on-outcome-in-off-pump-coronary-artery-bypass-surgery-patients-a-prospective-randomized-control-study
#7
Murali Chakravarthy, Dattatreya Prabhakumar, Patil Thimmannagowda, Jayaprakash Krishnamoorthy, Antony George, Vivek Jawali
INTRODUCTION: While off pump coronary artery bypass surgery is practiced with an intention to reduce the morbidity associated with cardiopulmonary bypass, the resultant 'hypercoagulability' needs to be addressed. Complications such as cavitary thrombus possibly due to the hyper coagulability after off pump coronary artery bypass surgery have been described. Many clinicians use higher doses of heparin - up to 5 mg/kg in order to thwart this fear. Overall, there appears to be no consensus on the dose of heparin in off pump coronary artery bypass surgeries...
January 2017: Annals of Cardiac Anaesthesia
https://www.readbyqxmd.com/read/28073784/platelets-and-neutrophil-extracellular-traps-collaborate-to-promote-intravascular-coagulation-during-sepsis-in-mice
#8
Braedon McDonald, Rachelle P Davis, Seok-Joo Kim, Mandy Tse, Charles T Esmon, Elzbieta Kolaczkowska, Craig N Jenne
Neutrophil extracellular traps (NETs; webs of DNA coated in anti-microbial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multi-color confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28069838/incidence-of-atrial-fibrillation-detected-by-continuous-rhythm-monitoring-after-acute-myocardial-infarction-in-patients-with-preserved-left-ventricular-ejection-fraction-results-of-the-arrest-study
#9
Alexander Romanov, Martin Martinek, Helmut Pürerfellner, Shaojie Chen, Mirko De Melis, Igor Grazhdankin, Dmitry Ponomarev, Denis Losik, Artem Strelnikov, Vitaliy Shabanov, Alexander Karaskov, Evgeny Pokushalov
AIMS: Cardiac arrhythmias following acute myocardial infarction (AMI) can be associated with major adverse cardiovascular events. Data on the "real incidence" of post-MI arrhythmias are limited. We aimed to determine the rate and burden of cardiac arrhythmias by the use of insertable cardiac monitors (ICM) in patients with preserved left ventricular ejection fraction (LVEF) after AMI. METHODS AND RESULTS: In this prospective observational study, patients with LVEF ≥40% who underwent PCI within 7 days following AMI were enrolled to receive an ICM...
January 8, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#10
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28062209/thromboelastogram-does-not-detect-pre-injury-anticoagulation-in-acute-trauma-patients
#11
Jawad T Ali, Mitchell J Daley, Nina Vadiei, Zachary Enright, Joseph Nguyen, Sadia Ali, Jayson D Aydelotte, Pedro G Teixeira, Thomas B Coopwood, Carlos Vr Brown
PURPOSE: Thromboelastography (TEG) has been recommended to characterize post-traumatic coagulopathy, yet no study has evaluated the impact of pre-injury anticoagulation (AC) on TEG variables. We hypothesized patients on pre-injury AC have a greater incidence of coagulopathy on TEG compared to those without AC. METHODS: This retrospective chart review evaluated all trauma patients admitted to an urban, level one trauma center from February 2011 to September 2014 who received a TEG within the first 24h...
December 26, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28062137/direct-oral-anti-coagulants-compared-with-vitamin-k-inhibitors-and-low-molecular-weight-heparin-for-the-prevention-of-venous-thromboembolism-in-patients-with-cancer-a-meta-analysis-study
#12
REVIEW
Natale Daniele Brunetti, Enrico Gesuete, Luisa De Gennaro, Michele Correale, Pasquale Caldarola, Antonio Gaglione, Matteo Di Biase
BACKGROUND: Prior meta-analysis studies showed that direct oral anticoagulants (DOAs) are as effective and safe as warfarin for the prevention of recurrences in patients with venous thrombo-embolism(VTE) and cancer. However, randomized studies also showed that low-molecular-weight-heparin (LMWH) performs better than warfarin in subjects with cancer. We therefore aimed to assess whether, even after pooling data with warfarin and LMWH, the use of DOAs remains safe and effective. METHODS: We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer...
December 27, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28060970/-evaluation-of-oral-anticoagulation-with-rivaroxaban-in-patients-with-new-onset-non-valvular-atrial-fibrillation
#13
Víctor Neira, Ramón Corbalán, Jaime Pereira, Olga Panes, Bernardita Garayar, Andrés Aizman, Silvana Llevaneras, Luis Villarroel
BACKGROUND: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. AIM: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. PATIENTS AND METHODS: Prospective study in patients with indication of anticoagulation...
September 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28060313/generation-of-human-monocyte-derived-dendritic-cells-from-whole-blood
#14
Wilfried Posch, Cornelia Lass-Flörl, Doris Wilflingseder
Dendritic cells (DCs) recognize foreign structures of different pathogens, such as viruses, bacteria, and fungi, via a variety of pattern recognition receptors (PRRs) expressed on their cell surface and thereby activate and regulate immunity. The major function of DCs is the induction of adaptive immunity in the lymph nodes by presenting antigens via MHC I and MHC II molecules to naïve T lymphocytes. Therefore, DCs have to migrate from the periphery to the lymph nodes after the recognition of pathogens at the sites of infection...
December 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28058802/increased-thrombin-generation-in-a-mouse-model-of-cancer-cachexia-is-partially-interleukin-6-dependent
#15
Caroline J Reddel, John D Allen, Anahid Ehteda, Ryland Taylor, Vivien M Y Chen, Jennifer L Curnow, Leonard Kritharides, Graham Robertson
BACKGROUND: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. OBJECTIVES: To assess if cancer cachexia altered coagulation state and if this was attributable to tumor IL-6 production...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28056565/characterization-of-aav-mediated-human-factor-viii-gene-therapy-in-hemophilia-a-mice
#16
Jenny A Greig, Qiang Wang, Amanda L Reicherter, Shu-Jen Chen, Alexandra L Hanlon, Christopher H Tipper, K Reed Clark, Samuel Wadsworth, Lili Wang, James M Wilson
Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, we performed an extensive study with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type...
January 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#17
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052306/laboratory-monitoring-of-parenteral-direct-thrombin-inhibitors
#18
Elizabeth M Van Cott, A Joshua Roberts, William E Dager
Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion...
January 4, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28045760/bleeding-risk-of-anti-thrombotic-treatment-in-patients-on-haemodialysis
#19
Eduardo Vázquez, Carmen Sánchez-Perales, Sonia Ortega, Teresa Vázquez-Sánchez, Enrique Quesada, Daniel Salas, Juan Carlos Fernández-Guerrero
BACKGROUND: The risk-benefit of anti-thrombotic treatment (ATT) has not been established in patients on dialysis. Our objective was to determine the influence of ATT on the risk of haemorrhage in patients on haemodialysis. METHODS: We included patients who began dialysis between 2003 and 2007. We determined the rates of fatal bleeding or bleeding leading to hospitalisation or transfusion. RESULTS: 221 patients were included. Over the follow-up period (45...
December 28, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28044251/novel-diagnostic-and-therapeutic-frontiers-in-thrombotic-anti-phospholipid-syndrome
#20
REVIEW
Savino Sciascia, Massimo Radin, Mario Bazzan, Dario Roccatello
The anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity, associated with a persistent positivity for anti-phospholipid antibodies (aPL). The current classification criteria for APS include three laboratory tests: lupus anti-coagulant (LA), anti-cardiolipin (aCL), and anti-β2 glycoprotein-I (β2GPI). To date, the therapeutic approach for thrombotic APS mainly centers on long-term anti-coagulation with a vitamin K antagonist (VKA). APS management may represent a challenge for the treating physicians...
January 2, 2017: Internal and Emergency Medicine
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