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https://www.readbyqxmd.com/read/28340300/synthesis-of-3-o-sulfated-oligosaccharides-to-understand-the-relationship-between-structures-and-functions-of-heparan-sulfate
#1
Zhangjie Wang, Po-Hung Hsieh, Yongmei Xu, David Thieker, Evangeline Juan En Chai, Shaoshuai Xie, Brian Cooley, Robert Woods, Lianli Chi, Jian Liu
The sulfation at the 3-OH position of glucosamine is an important modification in forming structural domains for heparan sulfate to enable its biological functions. Seven 3-O-sulfotransferase isoforms in the human genome are involved in the biosynthesis of 3-O-sulfated heparan sulfate. As a rare modification present in heparan sulfate, the availability of 3-O-sulfated oligosaccharides is very limited. Here, we report the use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides...
March 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28337077/antithrombin-iii-doses-rounded-to-available-vial-sizes-in-critically-ill-pediatric-patients
#2
Winifred M Stockton, Eimeira Padilla-Tolentino, Carolyn E Ragsdale
OBJECTIVES: Children have decreased levels of antithrombin III (AT III) compared to adults. These levels may be further decreased during acute illness. Administration of exogenous AT III can increase anticoagulant efficacy. The objective of this study was to evaluate AT III doses rounded to available vial sizes compared to partial vial doses in critically ill pediatric patients, including patients receiving extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT)...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28332273/reducing-the-incidence-of-hepatic-artery-thrombosis-in-pediatric-liver-transplantation-effect-of-microvascular-techniques-and-a-customized-anticoagulation-protocol
#3
William A Ziaziaris, Alexandre Darani, Andrew J A Holland, Angus Alexander, Jonathan Karpelowsky, Pasquale Barbaro, Michael Stormon, Edward O'Loughlin, Albert Shun, Gordon Thomas
We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986-2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008-2012, microvascular techniques were introduced...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28330182/efficient-single-step-chromatographic-purification-of-recombinant-human-antithrombin-rhat-from-saccharomyces-cerevisiae
#4
Maheswara Reddy Mallu, Sandeep Vemula, Srinivasa Reddy Ronda
Antithrombin (AT) is a glycoprotein that inactivates the several physiological target enzymes of coagulation system. The effect of purification strategies plays a crucial role in getting maximum recovery of yield, purity and biological activity of recombinant human antithrombin (rhAT). In the present work, the task of purifying rhAT from Saccharomyces cerevisiae BY4741 has been carried out using two different approaches such as cross flow filtration (CFF) system and chromatography methods. In the first approach, the protein was concentrated and partially purified through CFF to achieve maximum recovery yield and purity of 87 and 94 %, respectively...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28323357/characterisation-of-clotting-factors-anticoagulant-protein-activities-and-viscoelastic-analysis-in-healthy-donkeys
#5
A Perez-Ecija, F J Mendoza
BACKGROUND: Studies have demonstrated differences in commonly measured hemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. OBJECTIVES: To characterize hemostatic parameters in healthy donkeys and compare them to those of horses. STUDY DESIGN: Cross-sectional study. METHODS: Clotting Factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas...
March 21, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28322799/novel-method-for-measurement-of-heparin-anticoagulant-activity-using-spr
#6
Jing Zhao, Xinyue Liu, Anju Malhotra, Quanhong Li, Fuming Zhang, Robert J Linhardt
A novel method has been developed for the easy measurement of heparin's anticoagulant activity using surface plasmon resonance. The anticoagulant activity of target heparin was evaluated by measuring the competitive antithrombin III binding of analyte heparin in the solution phase and USP heparin immobilized on chip surface. Heparins, obtained from different animal sources, and low molecular weight heparins were analyzed. The results were reproducible and correlated well with the results of chromogenic assays (correlation coefficient r = 0...
March 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28319440/markers-of-blood-coagulation-and-fibrinolysis-in-patients-with-early-and-delayed-microsurgical-reconstructions-in-the-lower-extremities
#7
Oliver Kloeters, Dalibor Vasilic, Pieter Hupkens, Dietmar Ulrich
BACKGROUND: In this study, markers of coagulation and fibrinolysis were assessed during early and delayed microsurgical reconstruction in patients with traumatic defects of their lower legs to analyse whether an imbalance of the hemostasis after trauma might predispose the development of vascular complications. METHODS: The prospective study included 70 patients. In 35 patients, surgery was performed within 72 hours after injury. In 35 other patients, delayed free flap transfer was performed between 14-21 days after trauma...
March 20, 2017: Journal of Plastic Surgery and Hand Surgery
https://www.readbyqxmd.com/read/28317410/sex-hormone-binding-globulin-and-antithrombin-iii-activity-in-women-with-oral-ultra-low-dose-estradiol
#8
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Kanako Yoshida, Takeshi Kato, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki, Minoru Irahara
Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group...
March 20, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28317092/serpinc1-gene-mutations-in-antithrombin-deficiency
#9
René Mulder, F Nanne Croles, André B Mulder, James A Huntington, Karina Meijer, Michaël V Lukens
Existing evidence suggests that in most cases antithrombin deficiency can be explained by mutations in its gene, SERPINC1. We investigated the molecular background of antithrombin deficiency in a single centre family cohort study. We included a total of 21 families comprising 15 original probands and sixty-six relatives, 6 of who were surrogate probands for the genetic analysis. Antithrombin activity and antigen levels were measured. The heparin-antithrombin binding ratio assay was used to distinguish between the different subtypes of type II antithrombin deficiency...
March 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28304137/influence-of-apixaban-on-commonly-used-coagulation-assays-results-from-the-belgian-national-external-quality-assessment-scheme
#10
M Van Blerk, E Bailleul, B Chatelain, A Demulder, K Devreese, J Douxfils, M Jacquemin, K Jochmans, F Mullier, W Wijns, B China, K Vernelen, M R Soumali
INTRODUCTION: The Belgian national External Quality Assessment Scheme performed a survey to assess the effect of the direct oral anticoagulant apixaban on the coagulation assays prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin as performed with a large number of reagent/instrument combinations. METHODS: Four lyophilized plasma samples spiked with apixaban (0, 41, 94 and 225 ng/mL) were sent to the 195 Belgian and Luxembourg clinical laboratories performing coagulation testing...
March 17, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28303970/transient-desialylation-in-combination-with-a-novel-antithrombin-deficiency-causing-a-severe-and-recurrent-thrombosis-despite-anticoagulation-therapy
#11
Nuria Revilla, María Eugenia de la Morena-Barrio, Antonia Miñano, Raquel López-Gálvez, Mara Toderici, José Padilla, Ángel García-Avello, María Luisa Lozano, Dirk J Lefeber, Javier Corral, Vicente Vicente
An in-depth focused study of specific cases of patients with recurrent thrombosis may help to identify novel circumstances, genetic and acquired factors contributing to the development of this disorder. The aim of this study was to carry out a detailed and sequential analysis of samples from a patient suffering from early and recurrent venous and arterial thrombosis. We performed thrombophilic tests, biochemical, functional, genetic and glycomic analysis of antithrombin and other plasma proteins. The patient carried a new type I antithrombin mutation (p...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302625/silencing-of-anticoagulant-protein-c-evokes-low-incident-but-spontaneous-atherothrombosis-in-apolipoprotein-e-deficient-mice
#12
Amber B Ouweneel, Marco Heestermans, Robin A F Verwilligen, Marion J J Gijbels, Pieter H Reitsma, Miranda van Eck, Bart J M van Vlijmen
OBJECTIVE: Murine atherosclerosis models do not spontaneously develop atherothrombotic complications. We investigated whether disruption of natural anticoagulation allows preexisting atherosclerotic plaques to progress toward an atherothrombotic phenotype. APPROACH AND RESULTS: On lowering of plasma protein C levels with small interfering RNA (siProc) in 8-week Western-type diet-fed atherosclerotic apolipoprotein E-deficient mice, one out of 4 mice displayed a large, organized, and fibrin- and leukocyte-rich thrombus on top of an advanced atherosclerotic plaque located in the aortic root...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28301908/identification-of-cost-saving-opportunities-for-the-use-of-antithrombin-iii-in-adult-and-pediatric-patients
#13
Alana Ciolek, John Lindsley, Jessica Crow, Kristen Nelson-McMillan, David Procaccini
Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28300866/thrombotic-risk-according-to-serpinc1-genotype-in-a-large-cohort-of-subjects-with-antithrombin-inherited-deficiency
#14
Martine Alhenc-Gelas, Genevieve Plu-Bureau, Justine Hugon-Rodin, Véronique Picard, Marie-Helene Horellou
Inherited quantitative (type I) or qualitative (type II) antithrombin deficiency (ATD) due to mutations in the SERPINC1 gene is a well-known risk factor for venous thromboembolism. ATD may also increase risk for arterial thrombosis. Few studies have investigated risk for thrombosis according to mutations. We addressed this topic in a large retrospective cohort study of 540 heterozygous carriers of SERPINC1 mutations and compared risk for first venous or arterial thrombosis associated with carrying of different type II or type I mutations...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28294526/phase-1-dose-escalating-study-of-the-safety-pharmacokinetics-and-pharmacodynamics-of-activated-factor-x-i-16l
#15
Dana Parsons-Rich, Fei Hua, Gang Li, Constantino Kantaridis, Debra D Pittman, Steven Arkin
BACKGROUND: FXa(I16L) (PF-05230907) is a zymogen-like variant of activated coagulation factor X (FXa). It exhibits enhanced resistance to inactivation by endogenous inhibitors compared with wild-type FXa and restores hemostatic activity in nonclinical models of various bleeding conditions. OBJECTIVES: To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of FXa(I16L) , a phase 1, first-in-human, dose escalation clinical trial in healthy adult volunteers was conducted METHODS: Participants were assigned to 1 of 6 ascending single-dose cohorts (0...
March 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28288667/dual-inhibition-of-thrombin-and-activated-factor-x-attenuates-disseminated-intravascular-coagulation-and-protects-organ-function-in-a-baboon-model-of-severe-gram-negative-sepsis
#16
Herbert Schöchl, Martijn van Griensven, Stefan Heitmeier, Volker Laux, Ulrike Kipman, Jan Roodt, Soheyl Bahrami, Heinz Redl
BACKGROUND: Inhibition of procoagulant pathways may improve outcome in sepsis. We examined whether a dual short-acting thrombin (factor II) and factor X (FX)a inhibitor (SATI) ameliorates sepsis-induced disseminated intravascular coagulation (DIC) and is organ-protective. METHODS: Escherichia coli were infused for 2 h in 22 anesthetized baboons. The control (CO) group (n = 8) received sterile isotonic solution only. In the treatment groups, SATI was administered starting 15 minutes after the end of the bacterial exposure...
March 13, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28282887/new-insights-in-thrombin-inhibition-structure-activity-relationships-by-characterization-of-octadecasaccharides-from-low-molecular-weight-heparin
#17
Pierre A J Mourier, Olivier Y Guichard, Fréderic Herman, Philippe Sizun, Christian Viskov
Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin)...
March 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28274560/antithrombin-iii-is-associated-with-acute-liver-failure-in-patients-with-end-stage-heart-failure-undergoing-mechanical-circulatory-support
#18
Judith Hoefer, Hanno Ulmer, Juliane Kilo, Raimund Margreiter, Michael Grimm, Peter Mair, Elfriede Ruttmann
OBJECTIVE: There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. METHODS: A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria...
February 9, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28273401/hemostatic-abnormalities-in-dogs-with-naturally-occurring-heatstroke
#19
Yaron Bruchim, Efrat Kelmer, Adar Cohen, Carolina Codner, Gilad Segev, Itamar Aroch
OBJECTIVE: To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke. DESIGN: Prospective observational study. SETTING: University teaching hospital. ANIMALS: Thirty client-owned dogs with naturally occurring heatstroke. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP)...
March 8, 2017: Journal of Veterinary Emergency and Critical Care
https://www.readbyqxmd.com/read/28264746/extremely-refractory-kawasaki-disease-with-disseminated-intravascular-coagulation
#20
Young Kwon Koh, Jae Hee Lee, Yeong Bong Park
Disseminated intravascular coagulation is a rare complication of Kawasaki disease and appears in <0.1% of Kawasaki disease patients. We report a case of refractory Kawasaki disease complicated with disseminated intravascular coagulation and giant coronary aneurysm. A 5-month-old boy presented with Kawasaki disease with coagulopathy. Although the coagulopathy improved after fresh-frozen plasma and antithrombin-III administration, the fever persisted despite two rounds of intravenous immunoglobulin, along with intravenous methylprednisolone pulse therapy and infliximab administration...
March 7, 2017: Cardiology in the Young
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