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Sample records for anticoagulant activity induced

  1. Does plasmin have anticoagulant activity?

    Directory of Open Access Journals (Sweden)

    Jane Hoover-Plow

    2010-03-01

    Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood

  2. Heparin mimetics with anticoagulant activity.

    Science.gov (United States)

    Nahain, Abdullah Al; Ignjatovic, Vera; Monagle, Paul; Tsanaktsidis, John; Ferro, Vito

    2018-02-15

    Heparin, a sulfated polysaccharide belonging to the glycosaminoglycan family, has been widely used as an anticoagulant drug for decades and remains the most commonly used parenteral anticoagulant in adults and children. However, heparin has important clinical limitations and is derived from animal sources which pose significant safety and supply problems. The ever growing shortage of the raw material for heparin manufacturing may become a very significant issue in the future. These global limitations have prompted much research, especially following the recent well-publicized contamination scandal, into the development of alternative anticoagulants derived from non-animal and/or totally synthetic sources that mimic the structural features and properties of heparin. Such compounds, termed heparin mimetics, are also needed as anticoagulant materials for use in biomedical applications (e.g., stents, grafts, implants etc.). This review encompasses the development of heparin mimetics of various structural classes, including synthetic polymers and non-carbohydrate small molecules as well as sulfated oligo- and polysaccharides, and fondaparinux derivatives and conjugates, with a focus on developments in the past 10 years. © 2018 Wiley Periodicals, Inc.

  3. Antithrombotic/anticoagulant and anticancer activities of selected ...

    African Journals Online (AJOL)

    Nine plants available in the Eastern Cape Province of South Africa were tested for antithrombotic and/or anticoagulant activity. Organic (methanol) and aqueous (distilled water) extractions were performed on the various plant parts. The thrombin assay and clotting time assays (thrombin-induced and CaCl2-induced) were ...

  4. Monitoring Oral Anticoagulant Therapy: Measuring Coagulant Activity

    DEFF Research Database (Denmark)

    Attermann, Jorn

    daily anticoagulant therapy. The therapy necessitates close monitoring of coagulant activity, since excess doses of anticoagulant medicine may lead to life-threatening bleedings. Traditionally, patients on OAT are required to pay regular visits to a physician, who decides on drug dosage adjustments....... There is general agreement that the quality of the therapy is too low, and often unexpected fluctuations in the coagulant activity are seen. Recently, OAT based on patient self-management has become a realistic alternative by the availability of small portable whole blood coagulometers. An important part...... of the new concept is the training and continuous support and monitoring of the patients, and a center with these purposes has been established at Skejby Sygehus. The main instrument for monitoring the coagulant activity is the prothrombin time (PT). This is the time until clotting can be observed...

  5. Anticoagulant activity of ginger ( Zingiber officinale Rosc ...

    African Journals Online (AJOL)

    Background: Herbal medicines with anticoagulant therapeutic claims could serve as veritable sources of new oral anticoagulant drugs with possible wider safety margins than the currently available ones. Objectives: This work was aimed at evaluating a Ginger Rhizome Methanolic Extract in vivo in rats for its potential ...

  6. Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

    Science.gov (United States)

    Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

    2016-05-12

    The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

  7. [Factors influenceing the activity of oral anticoagulants].

    Science.gov (United States)

    González Caamaño, A; Díaz Barreiro, L A

    1976-01-01

    Anticoagulants are drugs capable to retard or even cancell the process of blood coagulation. They are many factors who influences the intensity and duration of oral anticoagulant acitivity, such as drugs, body constitution, physical agents, diseases, etc. The oral anticoagulants interacts with other drugs at differents levels: at the gut, at the plasma, modiffing the protein binding or the metabolism of such drugs, at the enzimatic induction or inhibition, or at unknown places with many other drugs. These paper deals with the description of such interactions.

  8. Anticoagulants

    Science.gov (United States)

    ... they last a long time. You participate in sports or other activities that put you at risk for bleeding or bruising. What are the side effects? Sometimes a medicine causes unwanted effects. These are ...

  9. Fibrinolytic and anticoagulative activities from the earthworm Eisenia foetida.

    Science.gov (United States)

    Hrzenjak, T; Popović, M; Bozić, T; Grdisa, M; Kobrehel, D; Tiska-Rudman, L

    1998-04-01

    Biologically active glycolipoprotein complex (G-90) isolated from whole earthworm tissue extract shows anticoagulative and fibrinolytic activities. We isolated two tyrosine like serine peptidases with molecular masses of 34 kDa (P I) and 23 kDa (P II), respectively. P I peptidase is autocatalytically degraded to P II. Both peptidases exhibit fibrinolytic and anticoagulative activities. The activity of P I is much higher. P I in concentration of 10(5) ng ml-1 of plasma shortened the physiological time of fibrin clot lysis by 54% and completely inhibited blood clotting at a concentration of 10(3) ng ml-1 of venous blood.

  10. Anticoagulant activity of a natural protein purified from Hypomesus olidus.

    Science.gov (United States)

    Gou, Mengxing; Wang, Liyan; Liu, Xuejun

    2017-05-01

    A novel anticoagulant protein (E-II-1) was separated and purified from Hypomesus olidus, a unique freshwater fish in northern China. E-II-1 had a molecular mass of approximately 40 kDa with no subunits. The high content of hydrophobic amino acids and negatively charged amino acids in E-II-1 demonstrated that the amino acid compositions might contribute to the anticoagulant activity. E-II-1 contained α-helices 16.75%, β-sheets 42.67%, β-turn 25.58% and random coil 15.00%. In vitro blood coagulation time assay, E-II-1 significantly prolonged the activated partial thrombin time in a dose-dependent manner. Results indicated that E-II-1 acted as anticoagulants through the endogenous pathway with an inhibition of FXa. The specific activity of E-II-1 was 103.50 U/mg at a concentration of 1.00 mg/mL. Therefore, E-II-1 might be one of the promising anticoagulants originated from natural food sources with more safety and less side effects.

  11. Synthesis and anticoagulant activity of the quaternary ammonium chitosan sulfates.

    Science.gov (United States)

    Fan, Lihong; Wu, Penghui; Zhang, Jinrong; Gao, Song; Wang, Libo; Li, Mingjia; Sha, Mingming; Xie, Weiguo; Nie, Min

    2012-01-01

    Quaternary ammonium chitosan sulfates with diverse degrees of substitution (DS) ascribed to sulfate groups between 0.52 and 1.55 were synthesized by reacting quaternary ammonium chitosan with an uncommon sulfating agent (N(SO(3)Na)(3)) that was prepared from sodium bisulfite (NaHSO(3)) through reaction with sodium nitrite (NaNO(2)) in the aqueous system homogeneous. The structures of the derivatives were characterized by FTIR, (1)H NMR and (13)C NMR. The factors affecting DS of quaternary ammonium chitosan sulfates which included the molar ratio of NaNO(2) to quaternary ammonium chitosan, sulfated temperature, sulfated time and pH of sulfated reaction solution were investigated in detail. Its anticoagulation activity in vitro was determined by an activated partial thromboplastin time (APTT) assay, a thrombin time (TT) assay and a prothrombin time (PT) assay. Results of anticoagulation assays showed quaternary ammonium chitosan sulfates significantly prolonged APTT and TT, but not PT, and demonstrated that the introduction of sulfate groups into the quaternary ammonium chitosan structure improved its anticoagulant activity obviously. The study showed its anticoagulant properties strongly depended on its DS, concentration and molecular weight. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  12. Anticoagulant activity of Moon jellyfish (Aurelia aurita) tentacle extract.

    Science.gov (United States)

    Rastogi, Akriti; Biswas, Sumit; Sarkar, Angshuman; Chakrabarty, Dibakar

    2012-10-01

    Moon jellyfish (Aurelia aurita) tentacle extract was studied for its anticoagulant activity in vitro. The Jellyfish Tentacle Extract (JFTE) showed very strong fibrinogenolytic activity by cleaving Aα and Bβ chain of fibrinogen molecule. The fibrinogenolytic activity was found to be stronger than some snake venom derived anticoagulants. JFTE also completely liquefied fibrin clots in 24 h. JFTE was found to contain both high and low molecular weight proteins/peptides. The fibrinogenolysis appears to be caused by high molecular weight fractions of the extract. It has been also noted that PMSF significantly reduced fibrinogenolytic activity and heating totally abolished it. Autolytic degradation of the high molecular weight protein was also noted. Autolysis slowed down, but did not abolish the fibrinogenolytic activity of the extract. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Anticoagulant activity of a dermatan sulfate from the skin of the shark Scyliorhinus canicula.

    Science.gov (United States)

    Dhahri, Manel; Mansour, Mohamed B; Bertholon, Isabelle; Ollivier, Véronique; Boughattas, Naceur A; Hassine, Mohsen; Jandrot-Perrus, Martine; Chaubet, Frédéric; Maaroufi, Raoui M

    2010-09-01

    A dermatan sulfate isolated from the shark Scyliorhinus canicula skin by enzymatic digestion followed by purification with anion exchange chromatography was identified by chondroitinase and nitrous acid treatment and partially characterized by Fourier-transform infrared spectroscopy. Dermatan sulfate was the major glycosaminoglycan and represented 75% of the polysaccharide fraction in the sharkskin. This dermatan sulfate had a 38.6 kDa average molecular weight and 23% sulfate content. The anticoagulant action of this dermatan sulfate was checked by several coagulometric and colorimetric assays such as the activated partial thromboplastin time, thrombin time, thrombin generation and heparin cofactor II and antithrombin-mediated inhibition of thrombin and compared with that of porcine intestinal mucosa dermatan sulfate. The effects on platelet activation and aggregation were investigated using flow cytometry and aggregometry, respectively. The dermatan sulfate prolonged activated partial thromboplastin time and thrombin time, delayed and inhibited thrombin generation in a concentration-dependent manner. The specific anticoagulant activity of the sharkskin dermatan sulfate was 43 UI/mg. The anticoagulant effect of sharkskin dermatan sulfate was higher than that of the porcine dermatan sulfate and was due to the potentiation of thrombin inhibition by heparin cofactor II. Moreover, it had no effect on platelet aggregation and activation induced by various agonists and thereby constitutes a potentially useful drug of interest in anticoagulant therapy.

  14. Anticoagulant Activity of Low-Molecular Weight Compounds from Heterometrus laoticus Scorpion Venom

    Directory of Open Access Journals (Sweden)

    Thien Vu Tran

    2017-10-01

    Full Text Available Scorpion venoms are complex polypeptide mixtures, the ion channel blockers and antimicrobial peptides being the best studied components. The coagulopathic properties of scorpion venoms are poorly studied and the data about substances exhibiting these properties are very limited. During research on the Heterometrus laoticus scorpion venom, we have isolated low-molecular compounds with anticoagulant activity. Determination of their structure has shown that one of them is adenosine, and two others are dipeptides LeuTrp and IleTrp. The anticoagulant properties of adenosine, an inhibitor of platelet aggregation, are well known, but its presence in scorpion venom is shown for the first time. The dipeptides did not influence the coagulation time in standard plasma coagulation tests. However, similarly to adenosine, both peptides strongly prolonged the bleeding time from mouse tail and in vitro clot formation in whole blood. The dipeptides inhibited the secondary phase in platelet aggregation induced by ADP, and IleTrp decreased an initial rate of platelet aggregation induced by collagen. This suggests that their anticoagulant effects may be realized through the deterioration of platelet function. The ability of short peptides from venom to slow down blood coagulation and their presence in scorpion venom are established for the first time. Further studies are needed to elucidate the precise molecular mechanism of dipeptide anticoagulant activity.

  15. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    Science.gov (United States)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  16. [Dependence of the anticoagulant activity of starch and inulin on their degree of sulfonation].

    Science.gov (United States)

    Drozd, N N; Torlopov, M A; Kuzhim, A A; Makarov, V A

    2012-01-01

    We have studied a relationship between the degree of sulfonation and anticoagulant activity of starch from Solanum tuberosum (molecular weight, 25000-30000 Da; sulfonation degree, 0.4-2.5) and inulin from Helianthus tuberosus (molecular weight, 7000-8000 Da; sulfonation degree, 0.6-1.6). Starch and inulin sulfates (i) increased the time of appearance of fibrin clots in plasma in coagulometric tests and (ii) reduced (via antithrombin) the rate of thrombin-induced hydrolysis of a chromogen substrate. The antithrombin (aIIa) activity of starch sulfates reached 16.8-70.0 IU/mg and the activity against factor Xa (aXa activity) was 2.3-16.6 IU/mg. The antithrombin activity of inulin sulfates was within 5.5-11.4 IU/mg and the activity against factor Xa (aXa activity) was within 0-1.4 IU/mg. An increase in the degree of sulfonation led to a growth in the anticoagulant activity of starch sulfates. The anticoagulant activity of starch sulfates and inulin sulfate with sulfonation degree 1.0 is mediated by antithrombin, which is the plasma inhibitor of serine proteases.

  17. Sulfonation and anticoagulant activity of botryosphaeran from Botryosphaeria rhodina MAMB-05 grown on fructose.

    Science.gov (United States)

    Mendes, Simone Ferreira; dos Santos, Osvaldo; Barbosa, Aneli M; Vasconcelos, Ana Flora D; Aranda-Selverio, Gabriel; Monteiro, Nilson K; Dekker, Robert F H; Sá Pereira, Mariana; Tovar, Ana Maria F; Mourão, Paulo A de Souza; da Silva, Maria de Lourdes Corradi

    2009-10-01

    Botryosphaeran (EPS(FRU)), an exopolysaccharide of the beta-(1-->3,1-->6)-d-glucan type with 31% branching at C-6, is produced by the fungus Botryosphaeria rhodina MAMB-05 when grown on fructose as carbon source. Botryosphaeran was derivatized by sulfonation to induce anticoagulant activity. The effectiveness of the sulfonation reaction by chlorosulfonic acid in pyridine was monitored by the degree of substitution and FT-IR analysis of the sulfonated EPS(FRU) (once sulfonated, EPS(FRUSULF); and re-sulfonated, EPS(FRURESULF)). Activated partial thromboplastin time (APTT) and thrombin time (TT) tests of EPS(FRURESULF) indicated significant in vitro anticoagulant activity that was dose-dependent. EPS(FRU) did not inhibit any of the coagulation tests.

  18. Physicochemical properties and anticoagulant activity of polyphenols derived from Lachnum singerianum

    Directory of Open Access Journals (Sweden)

    Shuai Zong

    2017-10-01

    Full Text Available In this study, polyphenols (LSP were obtained from the fermentation broth of Lachnum singerianum. Two fractions were isolated by Sephadex LH-20 chromatographic column, and the primary fraction (LSP-1 was collected. The comprehensive physicochemical properties of phenolic acids and polyhydroxy phenolic compounds of LSP-1 were determined by UV-visible spectroscopy, Fourier transform infrared spectroscopy, and gas chromatography–mass spectrometry. Results of anticoagulant activity assay in vitro showed that LSP-1 could lengthen prothrombin time, activated partial thromboplastin time, and thrombin time of mouse plasma. In addition, anticoagulant activity results in vivo showed that high dose of LSP-1 could significantly prolong bleeding time, coagulation time, prothrombin time, activated partial thromboplastin time, and thrombin time of hypercoagulable mice induced by adrenaline, reduce the content of fibrinogen and enhance antithrombin III activity. All results indicated that the LSP-1 could serve well as an anticoagulant, and might be used as a potential natural drug candidate for thrombosis.

  19. The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    We report a kindred with heritable protein C (PC) deficiency in which two siblings with severe thrombosis showed a composite type I and IIb PC deficiency phenotype, identified using commercial PC assays (proband: PC antigen 42 u\\/dl, amidolytic activity 40 u\\/dl, anticoagulant activity 9 u\\/dl). The independent PROC nucleotide variations c.669C>A (predictive of Ser181Arg) and c.131C>T (predictive of Asn2Ile) segregated with the type I and type IIb PC deficiency phenotypes respectively, but co-segregated in the siblings with severe thrombosis. Soluble thrombomodulin (sTM)-mediated inhibition of plasma thrombin generation from an individual with PC-Asn2Ile was lower (endogenous thrombin potential (ETP) 56 +\\/- 1% that of ETP determined without sTM) than control plasma (ETP 15 +\\/- 2%) indicating reduced PC anticoagulant activity. Recombinant APC-Asn2Ile exhibited normal amidolytic activity but impaired anticoagulant activity. Protein S (PS)-dependent anticoagulant activity of recombinant APC-Asn2Ile and binding of recombinant APC-Asn2Ile to endothelial protein C receptor (EPCR) were reduced compared to recombinant wild-type APC. Asn2 lies within the omega-loop of the PC\\/APC Gla domain and this region is critical for calcium-induced folding and subsequent interactions with anionic phospholipids, EPCR and PS. The disruption of these interactions in this naturally-occurring PC variant highlights their collective importance in mediating APC anticoagulant activity in vivo.

  20. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

    Science.gov (United States)

    Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

    2017-01-01

    Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

  1. A plasma coagulation assay for an activated protein C-independent anticoagulant activity of protein S

    NARCIS (Netherlands)

    van Wijnen, M.; van 't Veer, C.; Meijers, J. C.; Bertina, R. M.; Bouma, B. N.

    1998-01-01

    To study the physiological importance of the activated protein C (APC)-independent anticoagulant activity of protein S, we developed an assay specific for this activity. The ability of protein S to prolong the clotting time in an APC-independent way was expressed as the ratio of the clotting time in

  2. Human Protein C produces anticoagulation and increased fibrinolytic activity in the cat

    International Nuclear Information System (INIS)

    Burdick, M.D.; Schaub, R.G.

    1986-01-01

    The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the Nembutal anesthetized cat was assessed. Human Protein C was activated by incubation with thrombin or by passage over a column of thrombin immobilized on CNBr Sepharose 4B. Cats were given bolus i.v. injections of either vehicle or PCa in a dose range of 3-16 μg/mL of calculated whole body volume. Citrated blood samples (9:1) were taken from a femoral vein prior to and at 5, 10, 20, 30, 60, 120, and 180 min. after PCa. Activated partial thromboplastin time (APTT), thrombin time (TT) euglobulin clot lysis (ECLT) and I-125 fibrin release (FR) was measured. Vehicle treated cats had no change in any parameter. PCa produced a dose and time dependent prolongation of APTT while TT was unchanged. Anticoagulation was evident immediately after PCa infusion and began to normalize within 20 min. Fibrinolytic activity measured by ECLT and FR was also stimulated by PCa but was not evident until 40-60 minutes after PCa injection. The results show that human PCa induces anticoagulation effects in the cat similar to other species. However, stimulation of fibrinolysis requires a longer period of time before expression. This delay of fibrinolytic stimulation should be considered when assessing the effects of human Protein C in other species

  3. Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands.

    Science.gov (United States)

    Rao, Narayanam V; Argyle, Brian; Xu, Xiaoyu; Reynolds, Paul R; Walenga, Jeanine M; Prechel, Margaret; Prestwich, Glenn D; MacArthur, Robert B; Walters, Bradford B; Hoidal, John R; Kennedy, Thomas P

    2010-07-01

    While heparin has been used almost exclusively as a blood anticoagulant, important literature demonstrates that it also has broad anti-inflammatory activity. Herein, using low anti-coagulant 2-O,3-O-desulfated heparin (ODSH), we demonstrate that most of the anti-inflammatory pharmacology of heparin is unrelated to anticoagulant activity. ODSH has low affinity for anti-thrombin III, low anti-Xa, and anti-IIa anticoagulant activities and does not activate Hageman factor (factor XII). Unlike heparin, ODSH does not interact with heparin-platelet factor-4 antibodies present in patients with heparin-induced thrombocytopenia and even suppresses platelet activation in the presence of activating concentrations of heparin. Like heparin, ODSH inhibits complement activation, binding to the leukocyte adhesion molecule P-selectin, and the leukocyte cationic granular proteins azurocidin, human leukocyte elastase, and cathepsin G. In addition, ODSH and heparin disrupt Mac-1 (CD11b/CD18)-mediated leukocyte adhesion to the receptor for advanced glycation end products (RAGE) and inhibit ligation of RAGE by its many proinflammatory ligands, including the advanced glycation end-product carboxymethyl lysine-bovine serum albumin, the nuclear protein high mobility group box protein-1 (HMGB-1), and S100 calgranulins. In mice, ODSH is more effective than heparin in reducing selectin-mediated lung metastasis from melanoma and inhibits RAGE-mediated airway inflammation from intratracheal HMGB-1. In humans, 50% inhibitory concentrations of ODSH for these anti-inflammatory activities can be achieved in the blood without anticoagulation. These results demonstrate that the anticoagulant activity of heparin is distinct from its anti-inflammatory actions and indicate that 2-O and 3-O sulfate groups can be removed to reduce anticoagulant activity of heparin without impairing its anti-inflammatory pharmacology.

  4. Anticoagulant drugs increase natural killer cell activity in lung cancer

    Czech Academy of Sciences Publication Activity Database

    Bobek, M.; Boubelík, Michael; Fišerová, Anna; Luptovcová, Martina; Vannucci, Luca; Kacprzak, G.; Kolodzej, J.; Majewski, A.M.; Hoffman, R. M.

    2005-01-01

    Roč. 47, č. 2 (2005), s. 215-223 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z5052915 Keywords : anticoagulant drugs * lung cancer * NK cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.172, year: 2005

  5. Susceptibility and resistance to experimental autoimmune encephalomyelitis and neuritis in the guinea pig correlate with the induction of procoagulant and anticoagulant activities.

    Science.gov (United States)

    Geczy, C L; Roberts, I M; Meyer, P; Bernard, C C

    1984-12-01

    Activation of macrophage procoagulant activity (MPCA) is involved in the manifestation of EAE and EAN in susceptible guinea pigs and provides a mechanism for the deposition of fibrin, which is a feature of histologic lesions of EAE. Peritoneal exudate cells (PEC) from susceptible (strain 13) guinea pigs immunized with either central or peripheral nervous tissue antigens produce procoagulant activity when incubated with the immunogen in vitro. The production of the procoagulant is quantitative and antigen-specific and is maximal at the time of clinical signs of the disease. After recovery, the production of procoagulant activity decreased. The MPCA test was able to discriminate the biochemical differences existing between chicken and mammalian peripheral nerve proteins, thus providing a quantitative and sensitive indicator of cell-mediated immunity in EAE and EAN. The autoimmune response to brain and nerve antigens in nonsusceptible (strain 2) guinea pigs was coincident with the antigen-specific production of a cell-bound anticoagulant activity by stimulated mononuclear cells. The production of anticoagulant activity followed the same sequence of time changes after immunization as that of the MPCA in susceptible guinea pigs, and high immunizing doses of nerve antigens induced high levels of anticoagulant activity. The same cells produced high levels of procoagulant when incubated with tuberculin or lipopolysaccharide. The recalcification time of normal plasma was prolonged by the anticoagulant, and the decreased clotting time of plasma induced by the procoagulant activity obtained by incubating sensitized strain 13 PEC with myelin basic protein was suppressed by the anticoagulant produced by culturing sensitized strain 2 PEC with myelin basic protein. Preliminary evidence indicates that the anticoagulant has properties similar to antithrombin III. The anticoagulant could play a role in the control of effector cell function, and therefore in recovery from clinical

  6. Evaluation of morning glory (Jacquemontia tamnifolia (L.) Griseb) leaves for antioxidant, antinociceptive, anticoagulant and cytotoxic activities.

    Science.gov (United States)

    Hossain, Mohammad Shahadat; Reza, A S M Ali; Rahaman, Md Masudur; Nasrin, Mst Samima; Rahat, Mohammed Rasib Uddin; Islam, Md Rabiul; Uddin, Md Josim; Rahman, Md Atiar

    2018-01-05

    The present study was planned to investigate the phytochemical, antioxidant, antinociceptive, anticoagulant and cytotoxic activities of the Jacquemontia tamnifolia (L.) Griseb leaf methanol extract (MExJT) in the laboratory using both in vitro and in vivo methods. Phytochemical values, namely, total phenolic and flavonoid contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect and FeCl3 reducing power effects, were studied by established methods. In vivo antinociceptive activity was performed by acidic acid-induced writhing test and formalin-induced pain test on Swiss albino mice at doses of 125, 250 and 500 mg/kg body weight. The clot lysis and brine shrimp lethality bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities of the plant extract, respectively. Phytochemical screening illustrates the presence of tannins, saponins, flavonoids, gums and carbohydrates, steroids, alkaloids and reducing sugars in the extract. The results showed the total phenolic content (146.33 g gallic acid equivalents/100 g extract) and total flavonoid content (133.33 g quercetin/100 g). Significant (pacetic acid-induced writhing test and formalin-induced pain models in Swiss albino mice with doses of 125, 250 and 500 mg/kg body weight. Significant (panalgesic activity. The results also demonstrate that MExJT has moderate thrombolytic and lower cytotoxic properties that may warrant further exploration.

  7. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  8. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  9. An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

    Science.gov (United States)

    Ursuegui, Sylvain; Recher, Marion; Krężel, Wojciech; Wagner, Alain

    2017-05-01

    Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This `Click & Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

  10. A comparative study on anticoagulant activities of three Chinese herbal medicines from the genus Panax and anticoagulant activities of ginsenosides Rg1 and Rg2.

    Science.gov (United States)

    Li, C T; Wang, H B; Xu, B J

    2013-08-01

    Chemical compositions of three herbal plants from the family Araliaceae genus Panax [Panax ginseng C. A. Mey, P. quinquefolius L. and P. notoginseng (Burk.) F. H. Chen] are quite similar; however, their medicinal natures vary greatly. The reason for differences has been explained in traditional Chinese medicine theory and partially verified by modern pharmacological investigations, such as antiplatelet aggregation. Aside from platelet aggregation, a variety of plasma coagulation factors are also involved in blood coagulation. The anticoagulation profiles of three herbs have not been investigated. The current research compared the inhibitory effects of three herbal extracts from Panax spp. and the purified ginsenosides from P. ginseng on blood coagulation. Human plasma was mixed with the water extracts (0.05 and 0.1 mg/mL) from roots of P. ginseng, P. quinquefolius and P. notoginseng and ginsenosides Rg1 and Rg2 (0.05 and 0.1 mg/mL), the blood clotting time of activated partial thromboplastin, prothrombin and thrombin were measured by a biochemical analyzer. The water extracts (0.05 mg/mL) of P. ginseng, P. quinquefolius and P. notoginseng could significantly extend blood clotting time as compared to the control group. Among three herbal medicines, 0.05 mg/mL of water extract from P. ginseng exhibited the strongest anticoagulation effects, followed by P. notoginseng, while P. quinquefolius presented the weakest effects. Both ginsenosides Rg1 and Rg2 could significantly extend blood clotting time in all three tests; ginsenoside Rg2 exhibited relative stronger anticoagulation effects as compared to ginsenoside Rg1. Among three herbs tested, P. ginseng as well as its active component ginsenoside Rg2 shows the strongest anticoagulation activity; current results indicate that P. ginseng and ginsenoside Rg2 have great potential to be an anticoagulation drug.

  11. Sulfated modification and anticoagulant activity of pumpkin (Cucurbita pepo, Lady Godiva) polysaccharide.

    Science.gov (United States)

    Liang, Li; Ao, Le; Ma, Tao; Ni, Yuanying; Liao, Xiaojun; Hu, Xiaosong; Song, Yi

    2018-01-01

    Sulfated modification of pumpkin polysaccharide using CAS with pyridines as catalysts under different conditions was conducted to obtain different degrees of sulfation on a laboratory scale. Anticoagulant activities of pumpkin polysaccharide and its sulfated derivatives were also investigated employing various established in vitro systems. Results showed that addition of high ratio of CAS/pyridine under constant conditions could increase the degree of substitution. Sulfate substitution was further confirmed by the FT-IR and 13 C NMR analysis. The d f values between 2.11-2.73 indicated the relatively expanded conformation of the sulfated derivatives. The sulfated polysaccharides showed higher anticoagulant activities through activated partial thrombosis time (aPTT), thrombin time (TT), prothrombin time (PT) and anti-Xa activity assay, which revealed that better anticoagulant activities could be obtained when DS remained higher and M w maintained in a moderate range. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A New Route of Fucoidan Immobilization on Low Density Polyethylene and Its Blood Compatibility and Anticoagulation Activity

    Directory of Open Access Journals (Sweden)

    Kadir Ozaltin

    2016-06-01

    Full Text Available Beside biomaterials’ bulk properties, their surface properties are equally important to control interfacial biocompatibility. However, due to the inadequate interaction with tissue, they may cause foreign body reaction. Moreover, surface induced thrombosis can occur when biomaterials are used for blood containing applications. Surface modification of the biomaterials can bring enhanced surface properties in biomedical applications. Sulfated polysaccharide coatings can be used to avoid surface induced thrombosis which may cause vascular occlusion (blocking the blood flow by blood clot, which results in serious health problems. Naturally occurring heparin is one of the sulfated polysaccharides most commonly used as an anticoagulant, but its long term usage causes hemorrhage. Marine sourced sulfated polysaccharide fucoidan is an alternative anticoagulant without the hemorrhage drawback. Heparin and fucoidan immobilization onto a low density polyethylene surface after functionalization by plasma has been studied. Surface energy was demonstrated by water contact angle test and chemical characterizations were carried out by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Surface morphology was monitored by scanning electron microscope and atomic force microscope. Finally, their anticoagulation activity was examined for prothrombin time (PT, activated partial thromboplastin time (aPTT, and thrombin time (TT.

  13. Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy.

    Directory of Open Access Journals (Sweden)

    John W Avery

    Full Text Available Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM, characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.

  14. Sulfonation of papain-treated chitosan and its mechanism for anticoagulant activity.

    Science.gov (United States)

    Suwan, Jiraporn; Zhang, Zhenqing; Li, Boyangzi; Vongchan, Preeyanat; Meepowpan, Puttinan; Zhang, Fuming; Mousa, Shaker A; Mousa, Shaymaa; Premanode, Bhusana; Kongtawelert, Prachya; Linhardt, Robert J

    2009-07-06

    The novel low-molecular-weight chitosan polysulfate (MW 5120-26,200 Da) was prepared using the depolymerization of chitosan with papain (EC. 3.4.22.2). The sulfonation of depolymerized products was performed using chlorosulfonic acid in N,N-dimethylformamide under semi-heterogeneous conditions. The structures of the products were characterized by FTIR, (13)C NMR, and (1)H NMR (1D, 2D NMR) spectroscopy. The present study sheds light on the mechanism of anticoagulant activity of chitosan polysulfate. Anticoagulant activity was investigated by an activated partial thromboplastin assay, a thrombin time assay, a prothrombin time assay, and thrombelastography. Surface plasmon resonance also provided valuable data for understanding the relationship between the molecular binding of sulfated chitosan to two important blood clotting regulators, antithrombin III and heparin cofactor II. These results show that the principal mechanism by which this chitosan polysulfate exhibits anticoagulant activity is mediated through heparin cofactor II and is dependent on polysaccharide molecular weight.

  15. Physical activity and risk of bleeding in elderly patients taking anticoagulants.

    Science.gov (United States)

    Frey, P M; Méan, M; Limacher, A; Jaeger, K; Beer, H-J; Frauchiger, B; Aschwanden, M; Rodondi, N; Righini, M; Egloff, M; Osterwalder, J; Kucher, N; Angelillo-Scherrer, A; Husmann, M; Banyai, M; Matter, C M; Aujesky, D

    2015-02-01

    Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy. © 2014 International Society on Thrombosis and Haemostasis.

  16. Femoral Nerve Palsy due to Anticoagulant Induced Retroperitoneal Hematoma

    Science.gov (United States)

    Gurbuz, Orcun; Ercan, Abdulkadir; Kumtepe, Gencehan; Karal, İlker Hasan; Velioglu, Yusuf; Ener, Serdar

    2014-01-01

    A forty-one-year-old man who, sought evaluation for a sudden hip flexion contracture and groin pain with a history of mechanical mitral valve replacement, had been misdiagnosed and treated as having lumbar discopathy for two days. This patient finally was diagnosed with compressive femoral neuropathy due to warfarin-induced retroperitoneal hematoma and successfully managed nonoperatively. This case is reported in order to draw attention to this rare presentation. PMID:25386195

  17. Femoral Nerve Palsy due to Anticoagulant Induced Retroperitoneal Hematoma

    Directory of Open Access Journals (Sweden)

    Orcun Gurbuz

    2014-01-01

    Full Text Available A forty-one-year-old man who, sought evaluation for a sudden hip flexion contracture and groin pain with a history of mechanical mitral valve replacement, had been misdiagnosed and treated as having lumbar discopathy for two days. This patient finally was diagnosed with compressive femoral neuropathy due to warfarin-induced retroperitoneal hematoma and successfully managed nonoperatively. This case is reported in order to draw attention to this rare presentation.

  18. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor.

    Science.gov (United States)

    Schultz, Nina Haagenrud; Tran, Hoa Thi Tuyet; Bjørnsen, Stine; Henriksson, Carola Elisabeth; Sandset, Per Morten; Holme, Pål Andre

    2017-01-01

    An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons. Blood samples from rivaroxaban-treated patients ( n =  50) were spiked with PCC, aPCC and rFVIIa at concentrations imitating 80%, 100% and 125% of suggested therapeutic doses. The reversal effect was assessed by thromboelastometry in whole blood and a thrombin generation assay (TGA) in platelet-poor plasma. Samples from healthy subjects ( n =  40) were included as controls. In thromboelastometry measurements, aPCC and rFVIIa had a superior effect to PCC in reversing the rivaroxaban-induced lenghtening of clotting time (CT). aPCC was the only haemostatic agent that shortened the CT down to below the control level. Compared to healthy controls, patients on rivaroxaban also had a prolonged lag time and decreased peak concentration, velocity index and endogenous thrombin potential (ETP) in platelet-poor plasma. aPCC reversed these parameters more effectively than rFVIIa and PCC. There were no differences in efficacy between 80%, 100% and 125% doses of aPCC. aPCC seems to reverse the anticoagulant effect of rivaroxaban more effectively than rFVIIa and PCC by evaluation with thromboelastometry and TGA in vitro.

  19. Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

    Science.gov (United States)

    Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

    2010-09-15

    Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

  20. Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran.

    Science.gov (United States)

    Ammollo, Concetta Tiziana; Semeraro, Nicola; Carratù, Maria Rosaria; Colucci, Mario; Semeraro, Fabrizio

    2016-02-01

    The antithrombin activity of unfractionated heparin (UFH) is offset by extracellular histones, which, along with DNA, represent a novel mediator of thrombosis and a structural component of thrombi. Here, we systematically evaluated the effect of histones, DNA, and histone-DNA complexes on the anticoagulant and profibrinolytic activities of UFH, its derivatives enoxaparin and fondaparinux, and the direct thrombin inhibitor dabigatran. Thrombin generation was assessed by calibrated automated thrombinography, inhibition of factor Xa and thrombin by synthetic substrates, tissue plasminogen activator-mediated clot lysis by turbidimetry, and thrombin-activatable fibrinolysis inhibitor (TAFI) activation by a functional assay. Histones alone delayed coagulation and slightly stimulated fibrinolysis. The anticoagulant activity of UFH and enoxaparin was markedly inhibited by histones, whereas that of fondaparinux was enhanced. Histones neutralized both the anti-Xa and anti-IIa activities of UFH and preferentially blocked the anti-IIa activity of enoxaparin. The anti-Xa activity of fondaparinux was not influenced by histones when analyzed by chromogenic substrates, but was potentiated in a plasma prothrombinase assay. Histones inhibited the profibrinolytic activity of UFH and enoxaparin and enhanced that of fondaparinux by acting on the modulation of TAFI activation by anticoagulants. Histone H1 was mainly responsible for these effects. Histone-DNA complexes, as well as intact neutrophil extracellular traps, impaired the activities of UFH, enoxaparin, and fondaparinux. Dabigatran was not noticeably affected by histones and/or DNA, whatever the assay performed. In conclusion, histones and DNA present in the forming clot may variably influence the antithrombotic activities of anticoagulants, suggesting a potential therapeutic advantage of dabigatran and fondaparinux over heparins. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures

    DEFF Research Database (Denmark)

    Rangnekar, Abhijit; Zhang, Alex M.; Shiyuan Li, Susan

    2012-01-01

    by a flexible single-strand linker, have been shown to possess anticoagulant activity. Here, we link multiple aptamers at programmed positions on DNA nanostructures to optimize spacing and orientation of the aptamers and thereby to maximize anticoagulant activity in functional assays. By judicious engineering...... of the DNA nanostructures, we have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than free aptamer. Reversal of the thrombin inhibition was also achieved by the use of single-stranded DNA antidotes, thus enabling significant control over......Control over thrombin activity is much desired to regulate blood clotting in surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have been used to inhibit thrombin activity and thus the coagulation cascade. Soluble DNA aptamers, as well as two different aptamers tethered...

  2. [Screening and identification of Bacillus pumilus producing double active protein of anticoagulation and thrombolysis].

    Science.gov (United States)

    Liu, Binghua; Luo, Yaxiong; Tao, Xuemei; Xie, Xiaoying; Ma, Xupan; Zhang, Lin

    2014-03-04

    The aim of this study was to screen bacteria that can produce antithrombotic. We screened the target bacteria on VY/4 plate and casein plate from more than 20 samples such as water, soil, rabbit manure, sheep manure and deadwood. We detected the antithrombotic activity by fibrin plate and fibrin tube. We identified the target bacteria by morphological characteristics, physical and chemical properties and 16S DNA sequence homology. We obtained 5 strains that can produce antithrombotic. We found that the extracellular protein of strain LDS33 shows both stronger fibrinolytic activity and stronger anticoagulation activity. According to the morphology, physiochemical properties, 16S DNA sequencing and phylogenetic tree, strain LDS33 is identified as Bacillus pumilus. Bacillus pumilus LDS33 can produce highly active anticoagulation and thrombolysis double active protein.

  3. Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients.

    Directory of Open Access Journals (Sweden)

    Takayoshi Tokutake

    Full Text Available The activated partial thromboplastin time (APTT assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003. Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant.

  4. Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients.

    Science.gov (United States)

    Tokutake, Takayoshi; Baba, Hisami; Shimada, Yuji; Takeda, Wataru; Sato, Keijiro; Hiroshima, Yuki; Kirihara, Takehiko; Shimizu, Ikuo; Nakazawa, Hideyuki; Kobayashi, Hikaru; Ishida, Fumihiro

    2016-01-01

    The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant.

  5. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2017-07-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  6. An Antithrombin-Heparin Complex Increases the Anticoagulant Activity of Fibrin Clots

    Directory of Open Access Journals (Sweden)

    Lesley J. Smith

    2008-01-01

    Full Text Available Clotting blood contains fibrin-bound thrombin, which is a major source of procoagulant activity leading to clot extension and further activation of coagulation. When bound to fibrin, thrombin is protected from inhibition by antithrombin (AT + heparin but is neutralized when AT and heparin are covalently linked (ATH. Here, we report the surprising observation that, rather than yielding an inert complex, thrombin-ATH formation converts clots into anticoagulant surfaces that effectively catalyze inhibition of thrombin in the surrounding environment.

  7. Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity and cytotoxicity.

    Science.gov (United States)

    Liang, Wanai; Mao, Xuan; Peng, Xiaohui; Tang, Shunqing

    2014-01-30

    In this paper, the structural effects of two main red seaweed polysaccharides (agarose and carrageenan) and their sulfated derivatives on the anticoagulant activity and cytotoxicity were investigated. The substitution position rather than the substitution degree of sulfate groups shows the biggest impact on both the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6-anhydro-α-d-Galp is the most favorable position for substitution, whereas C-6 of β-d-Galp is the most disadvantageous. Moreover, the secondary structures of glycans also play a key role in biological activities. These demonstrations warrant that the red seaweed polysaccharides should be seriously considered in biomedical applications after carefully tailoring the sulfate groups. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Depolymerized glycosaminoglycan and its anticoagulant activities from sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Yang, Jie; Wang, Yuanhong; Jiang, Tingfu; Lv, Lv; Zhang, Boyuan; Lv, Zhihua

    2015-01-01

    A controlled Cu(2+) catalytic free-radical depolymerization process of fucosylated chondroitin sulfate from sea cucumber Apostichopus japonicus was established. The results showed a good linear relationship between 1/Mw and time during the depolymerization. A series of fractions with different molecular weight were obtained, and the physicochemical properties of them were investigated and compared utilizing the chemical method, IR spectra and NMR spectra. The results showed no significant variations of the backbone and branches structures during the depolymerization. Furthermore, the anticoagulant activities of the depolymerized fractions were evaluated by the activated partial thromboplastin time (APTT). The APTT decreases in proportion to the molecular weight following a linear relationship and the prolongation of APTT activity requires at least oligosaccharide of 4 trisaccharide units (about 4000 Da). Their anticoagulant activity of low molecular weight fraction (Mw = 24,755 Da) is similar to LMWH with significantly less bleeding risk. The results suggest that the low molecular weight fraction could be used as a novel anticoagulant with less undesired side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

    Science.gov (United States)

    Sun, Yuhao; Chen, Xiaolin; Liu, Song; Yu, Huahua; Li, Rongfeng; Wang, Xueqin; Qin, Yukun; Li, Pengcheng

    2017-10-01

    Heparin has been used as an anticoagulant drug for many years, but it has significant side effects. In the search for good substitutes, low molecular weight (MW) polysaccharides from Sargassum fusiforme have been examined and confirmed to possess biological activities. Here, S. fusiforme polysaccharides (SFP) were extracted and subjected to a hydrogen peroxide (H2O2) oxidation method for the preparation of low-MW SFP (LSFP). The effects of temperature, pH, and H2O2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin (APTT), prothrombin (PT) and thrombin times (TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these effects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined effects. The details of this mechanism require further verification.

  10. Evaluation of optical coherence tomography for the measurement of the effects of activators and anticoagulants on the blood coagulation in vitro.

    Science.gov (United States)

    Xu, Xiangqun; Geng, Jinhai; Liu, Gangjun; Chen, Zhongping

    2013-08-01

    Optical properties of human blood during coagulation were studied using optical coherence tomography (OCT) and the parameter of clotting time derived from the 1/e light penetration depth (d(1/e)) versus time was developed in our previous work. In this study, in order to know if a new OCT test can characterize the blood-coagulation process under different treatments in vitro, the effects of two different activators (calcium ions and thrombin) and anticoagulants, i.e., acetylsalicylic acid (ASA, a well-known drug aspirin) and melagatran (a direct thrombin inhibitor), at various concentrations are evaluated. A swept-source OCT system with a 1300 nm center wavelength is used for detecting the blood-coagulation process in vitro under a static condition. A dynamic study of d1/e reveals a typical behavior due to coagulation induced by both calcium ions and thrombin, and the clotting time is concentration-dependent. Dose-dependent ASA and melagatran prolong the clotting times. ASA and melagatran have different effects on blood coagulation. As expected, melagatran is much more effective than ASA in anticoagulation by the OCT measurements. The OCT assay appears to be a simple method for the measurement of blood coagulation to assess the effects of activators and anticoagulants, which can be used for activator and anticoagulant screening.

  11. Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino) Gonad.

    Science.gov (United States)

    Zhao, Jun; Yang, Jingfeng; Song, Shuang; Zhou, Dayong; Qiao, Weizhou; Zhu, Ce; Liu, Shuyin; Zhu, Beiwei

    2016-06-08

    In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33), which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR) spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) compared to a saline control solution in a dosage-dependent manner. AGP33 exhibited an extension (p < 0.01) of APTT compared to the saline group at concentrations higher than 5 μg/mL. AGP33 exhibited higher anticoagulant activity than its desulfated product (AGP33-des) and BAGP33. The results showed that polysaccharide with higher molecular weight and sulfate content demonstrated greater anticoagulant activity.

  12. Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino Gonad

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    2016-06-01

    Full Text Available In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33 isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33, which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT, thrombin time (TT and prothrombin time (PT compared to a saline control solution in a dosage-dependent manner. AGP33 exhibited an extension (p < 0.01 of APTT compared to the saline group at concentrations higher than 5 μg/mL. AGP33 exhibited higher anticoagulant activity than its desulfated product (AGP33-des and BAGP33. The results showed that polysaccharide with higher molecular weight and sulfate content demonstrated greater anticoagulant activity.

  13. Sulfonation and anticoagulant activity of fungal exocellular β-(1→6)-D-glucan (lasiodiplodan).

    Science.gov (United States)

    Vasconcelos, Ana Flora D; Dekker, Robert F H; Barbosa, Aneli M; Carbonero, Elaine R; Silveira, Joana L M; Glauser, Bianca; Pereira, Mariana Sá; Corradi da Silva, Maria de Lourdes

    2013-02-15

    An exocellular β-(1→6)-D-glucan (lasiodiplodan) produced by a strain of Lasiodiplodia theobromae (MMLR) grown on sucrose was derivatized by sulfonation to promote anticoagulant activity. The structural features of the sulfonated β-(1→6)-D-glucan were investigated by UV-vis, FT-IR and (13)C NMR spectroscopy, and the anticoagulant activity was investigated by the classical coagulation assays APTT, PT and TT using heparin as standard. The content of sulfur and degree of substitution of the sulfonated glucan was 11.73% and 0.95, respectively. UV spectroscopy showed a band at 261 nm due to the unsaturated bond formed in the sulfonation reaction. Results of FT-IR and (13)C NMR indicated that sulfonyl groups were inserted on the polysaccharide. The sulfonated β-(1→6)-D-glucan presented anticoagulant activity as demonstrated by the increase in dose dependence of APTT and TT, and these actions most likely occurred because of the inserted sulfonate groups on the polysaccharide. The lasiodiplodan did not inhibit the coagulation tests. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Sulfated Polysaccharides Isolated from Cloned Grateloupia filicina and Their Anticoagulant Activity

    Directory of Open Access Journals (Sweden)

    Xiaolin Chen

    2015-01-01

    Full Text Available Sulfated polysaccharides (GSP were isolated from the cloned Grateloupia filicina which was cultured in Jiaozhou Bay, Qingdao, China. The yield of GSP was 15.75%. The total sugar and sulfate were 40.90 and 19.89%, respectively. And the average molecular weight was 11.7 KDa. The results of neutral sugar analysis showed that GSP was mainly sulfated polysaccharides of galactose. The experiments for activated partial thromboplastin time (APTT, prothrombin time (PT, and thrombin time (TT anticoagulant assays in vitro indicated that GSP was a good potential anticoagulant. Therefore, this study supplied new thought for the cloned Grateloupia filicina exploitation of high-value products.

  15. Bioassay-guided fractionation of Melastoma malabathricum Linn. leaf solid phase extraction fraction and its anticoagulant activity.

    Science.gov (United States)

    Khoo, Li Teng; Abdullah, Janna Ong; Abas, Faridah; Tohit, Eusni Rahayu Mohd; Hamid, Muhajir

    2015-02-24

    The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The active anticoagulant fraction of F3 was subjected to a series of chromatographic separation and spectroscopic analyses. Furthermore, the effect of the bioactive component(s) on the intrinsic blood coagulation pathway was studied through immediate and time incubation mixing studies. Through Activated Partial Thromboplastin Time (APTT) assay-guided fractionation, Subfraction B was considered the most potent anticoagulant fraction. Characterisation of Subfraction B indicated that anticoagulant activity could partly be due to the presence of cinnamic acid and a cinnamic acid derivative. APTT assays for both the immediate and time incubation mixing were corrected back into normal clotting time range (35.4-56.3 s). In conclusion, cinnamic acid and cinnamic acid derivative from Subfraction B were the first such compounds to be discovered from M. malabathricum Linn. leaf hot water crude extract that possess anticoagulant activity. This active anticoagulant Subfraction B prolonged blood clotting time by causing factor(s) deficiency in the intrinsic blood coagulation pathway.

  16. Anticoagulation activity of salivary gland extract of oriental blackfly Simulium indicum

    Directory of Open Access Journals (Sweden)

    Subhalaxmi Borah

    2014-05-01

    Conclusions: The present study demonstrated that the mode of action of the anticoagulant(s is mainly on the inhibition of thrombin and factor Xa along with other target factors of the coagulation cascade.

  17. Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

    Science.gov (United States)

    Maslow, Andrew; Chambers, Alison; Cheves, Tracey; Sweeney, Joseph

    2018-01-31

    Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. Prospective study. Tertiary care cardiovascular center. Eleven consecutive elective adult cardiac surgical patients. Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels 0.75 U/mL. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Synthesis of New DNA G-Quadruplex Constructs with Anthraquinone Insertions and Their Anticoagulant Activity

    DEFF Research Database (Denmark)

    Gouda, Alaa S.; Amine, Mahasen S.; Pedersen, Erik Bjerregaard

    2016-01-01

    anthraquinone linker led to a significant stabilization of the G-quadruplex structure upon replacing a T in each of two neighboring lateral TT loops and a 26.28 increase in thermal melting temperature was found. CD Spectra of the modified quadruplexes confirmed anti-parallel conformations in all cases under...... potassium buffer conditions as previously observed for TBA. Although the majority of the anthraquinone modified TBA analogues showed a decrease in clotting times in a fibrinogen clotting assay when compared to TBA, modified aptamers containing a 1,8-disubstituted anthraquinone linker replacing G8 or T9...... in the TGT loop showed improved anticoagulant activities. Molecular modeling studies explained the increased thermal melting temperatures of anthraquinone-modified G-quadruplexes....

  19. Novel branch patterns and anticoagulant activity of glycosaminoglycan from sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Yang, Jie; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

    2015-01-01

    A novel glucosidic pattern of fucose branches was found in the glycosaminoglycan from the sea cucumber Apostichopus japonicus in China. The methylation of desulfated/carboxyl-reduced polysaccharides and analysis of unsaturated disaccharides generated from the enzymolysis of the defucosed polysaccharides demonstrated that the branch is formed by one fucopyranosyl residue, 46.5% of which is linked through the O-3 position of β-D-glucuronic acid, while 8.7% and 43.9% are linked through the O-6 and O-4 positions of the N-acetylgalactosamine moiety. The β-D-glucuronic acid, N-acetyl-β-D-galactosamine, α-L-fucose and sulfate ester with the molecular ratio of 0.97:1.00:1.13:3.85 composed the backbone → 4)GlcUAβ(1 → 3)GalNAcβ(1 → and sulfated fucose branches. The sulfation patterns of fucose branches and the linkage pattern of the backbone structure were determined by 1/2 dimension NMR. The most abundant branch species were 2,4-di-O-sulfated and 3,4-di-O-sulfated fucose, but 4-mono-O-sulfated residue was also present. The structure of presently obtained glycosaminoglycan is different from that previously obtained from Stichopus japonicus (Kariya et al., Carbohyd. Res. 297 (1997) 273-279), which suggests that the structures of glycosaminoglycans from the same species of different regions somehow differ. The anticoagulant assay indicated that the polysaccharide possessed a high anticoagulant activity and the sulfated fucose branches were essential to the activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Dual antiplatelet and anticoagulant APAC prevents experimental ischemia-reperfusion-induced acute kidney injury.

    Science.gov (United States)

    Tuuminen, Raimo; Jouppila, Annukka; Salvail, Dan; Laurent, Charles-E; Benoit, Marie-Claude; Syrjälä, Simo; Helin, Heikki; Lemström, Karl; Lassila, Riitta

    2017-06-01

    Renal ischemia-reperfusion predisposes to acute kidney injury (AKI) and mortality. APAC, mast cell heparin proteoglycan mimetic is a potent dual antiplatelet and anticoagulant inhibiting thrombosis in several vascular models. Clinically relevant (0.06 and 0.13 mg/kg) and high (0.32 and 7.3 mg/kg) heparin doses of APAC and unfractionated heparin (UFH) were administered i.v. in pharmacological studies. Antithrombotic action of APAC and UFH was assessed with platelet aggregation to collagen, activated partial thromboplastin (APTT) and prothrombin (PT) times. Pharmacodynamics of [ 64 Cu]-APAC or -UFH were monitored by PET/CT. Next, APAC and UFH doses (0.06 and 0.13 mg/kg) were i.v. administered 10 min prior to renal ischemia-reperfusion injury (IRI) in rats. APAC in contrast to UFH inhibited platelet aggregation. During 0.06 and 0.13 mg/kg dose regimens APTT and PT remained at baseline, but at the high APTT prolonged fourfold to sixfold. Overall bio-distribution and clearance of APAC and UFH were similar. After bilateral 30-min renal artery clamping, creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin concentrations and histopathology indicated faster renal recovery by APAC (0.13 mg/kg). APAC, unlike UFH, prevented expression of innate immune ligand hyaluronan and tubulointerstitial injury marker Kim-1. Moreover, in severe bilateral 1-h renal artery clamping, APAC (0.13 mg/kg) prevented AKI, as demonstrated both by biomarkers and survival. Compatible with kidney protection APAC reduced the circulating levels of vascular destabilizing and pro-inflammatory angiopoietin-2 and syndecan-1. No tissue bleeding ensued. APAC and UFH were similarly eliminated via kidneys and liver. In contrast to UFH, APAC (0.13 mg/kg) was reno-protective in moderate and even severe IRI by attenuating vascular injury and innate immune activation.

  1. Structural Features and Anti-coagulant Activity of the Sulphated Polysaccharide SPS-CF from a Green Alga Capsosiphon fulvescens

    Czech Academy of Sciences Publication Activity Database

    Synytsya, A.; Choi, D. J.; Pohl, Radek; Na, Y. S.; Capek, P.; Lattová, E.; Taubner, T.; Choi, J. W.; Lee, C. W.; Park, J. K.; Kim, W. J.; Kim, S. M.; Lee, J.; Park, Y. I.

    2015-01-01

    Roč. 17, č. 6 (2015), s. 718-735 ISSN 1436-2228 Institutional support: RVO:61388963 Keywords : alga Maesaengi (Capsosiphon fulvescens) * ulvan * monosaccharide composition * structure * anti-coagulant activity Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.062, year: 2015

  2. Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

    Directory of Open Access Journals (Sweden)

    Soo Hyun Lee

    2016-05-01

    Full Text Available Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT and prothrombin time (PT in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (1, 33.2 ± 0.7 s and N-(4′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (2, 43.5 ± 0.6 s were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2 ± 0.7 s and 2 (43.5 ± 0.6 s were compared with heparin (62.5 ± 0.8 s in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo and on tail bleeding time (in vivo on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs. Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product.

  3. NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

    Science.gov (United States)

    Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

    2010-06-01

    The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

  4. Increased prothrombin activation in protein S-deficient plasma under flow conditions on endothelial cell matrix: an independent anticoagulant function of protein S in plasma

    NARCIS (Netherlands)

    van't Veer, C.; Hackeng, T. M.; Biesbroeck, D.; Sixma, J. J.; Bouma, B. N.

    1995-01-01

    Protein S is a vitamin K-dependent nonenzymatic coagulation factor involved in the regulation of activated protein C (aPC). In this study, we report an aPC-independent anticoagulant function of protein S in plasma under flow conditions. Plasma, anticoagulated with low-molecular-weight heparin

  5. Anticoagulant, Antioxidant and Antitumor Activities of Heterofucans from the Seaweed Dictyopteris delicatula

    Directory of Open Access Journals (Sweden)

    Hugo Alexandre Oliveira Rocha

    2011-05-01

    Full Text Available In the present study, six families of sulfated polysaccharides were obtained from seaweed Dictyopteris delicatula by proteolytic digestion, followed by acetone fractionation and molecular sieving on Sephadex G-100. Chemical analyses demonstrated that all polysaccharides contain heterofucans composed mainly of fucose, xylose, glucose, galactose, uronic acid, and sulfate. The fucans F0.5v and F0.7v at 1.0 mg/mL showed high ferric chelating activity (~45%, whereas fucans F1.3v (0.5 mg/mL showed considerable reducing power, about 53.2% of the activity of vitamin C. The fucan F1.5v presented the most prominent anticoagulant activity. The best antiproliferative activity was found with fucans F1.3v and F0.7v. However, F1.3v activity was much higher than F0.7v inhibiting almost 100% of HeLa cell proliferation. These fucans have been selected for further studies on structural characterization as well as in vivo experiments, which are already in progress.

  6. Anticoagulant Resistance

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte

    Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...

  7. Antibacterial, cytotoxicity and anticoagulant activities from Hypnea esperi and Caulerpa prolifera marine algae.

    Science.gov (United States)

    Selim, Samy; Amin, Abeer; Hassan, Sherif; Hagazey, Mohamed

    2015-03-01

    Extracts from 2 algal species (Hypnea esperi and Caulerpa prolifera) from Suez Canal region, Egypt were screened for the production of antibacterial compounds against some pathogenic bacteria. The bacteria tested included Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Aeromonas hydrophila, Bacillus subtilis and Staphylococcus aureus. Algal species displayed antibacterial activity. The methanolic extracts showed variable response by producing various zones of inhibition against studied bacteria. The tested Gram-negative bacteria were less affected by studied algal extracts than Gram-positive bacteria. We determined some biopotentials properties such as cytotoxicity and anticoagulant activity of most potent algal active extracts. The secondary metabolites of only Hypnea esperi algal extract effectively prevented the blood clotting to the extent of 120 seconds. Minimum inhibitory concentration (MIC) indicated that all potent tested algal extract C inhibits Bacillus subtilis and Staphylococcus aureus. Minimum bactericidal concentration (MBC) was between 1 and 1.4mg/ml. The algal isolates from Egypt have been found showing promising results against infectious bacteria instead of some synthetic antibiotics.

  8. Anticoagulant activity of a sulfated polysaccharide isolated from the green seaweed Caulerpa cupressoides

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2011-08-01

    Full Text Available The aim of this study was to evaluate certain molecular characteristics of a sulfated polysaccharide (SPs with anticoagulant properties, isolated from Caulerpa cupressoides (Chlorophyta. Crude SPs were extracted by proteolytic digestion (papain, followed by ion-exchange chromatography on a DEAE-cellulose column. The fractions obtained were analyzed for molecular mass, 0.5% agarose gel electrophoresis and chemical composition. The activated partial thromboplastin time (APTT test was applied using normal human plasma and standard heparin (HEP (193 IU mg-1. The yield was ~ 3%, and the chromatography procedure separated the material into three different SP fractions (F I, F II and F III, eluted at the concentrations of 0.50, 0.75 and 1.00 M of NaCl, respectively. Only fraction F II was active (24.62 IU mg-1, with high sulfate content (23.79% and number of molecular mass peaks. Therefore, the APTT of a fraction isolated from C. cupressoides was less potent than HEP.

  9. In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin

    Science.gov (United States)

    2011-01-01

    Background Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. Results Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. Conclusions These newly found

  10. lupus anticoagulants: pathophysiology, clinical

    African Journals Online (AJOL)

    2003-11-02

    Nov 2, 2003 ... report. East Afr. Med. J. 1998; 75:619-620. procainamide induced lupus anticoagulant. Acta Haematol. 13. Mateo, 1., Oliver, A., Borell, M. et al. Laboratory evaluation 1989; 82:50-52. and clinical characteristics of 2, 132 consecutive unselected 29. Rai, R., Cohen H., Dave M., and Regan, L. Randomised.

  11. Antioxidant and anticoagulant activity of sulfated polysaccharide from Gracilaria debilis (Forsskal).

    Science.gov (United States)

    Sudharsan, Sadhasivam; Subhapradha, Namasivayam; Seedevi, Palaniappan; Shanmugam, Vairamani; Madeswaran, Perumal; Shanmugam, Annaian; Srinivasan, Alagiri

    2015-11-01

    Sulfated polysaccharide was isolated from Gracilaria debilis and purified through gel chromatography and their molecular weight was determined through AGE and PAGE. The total sugars in the crude, fractionated and purified polysaccharide were estimated as 52.65%, 59.70% and 67.60%, respectively. The ash and moisture content of crude and purified polysaccharide was found to be 14.2% and 23.5% and the polysaccharide was free from protein contamination. The sulfate and uronic acid contents in the crude, fractionated and purified were estimated as 14.08%, 15.33% and 16.01% and 10.12%, 13.56%, 16.70%. The elemental composition including carbon (crude - 23.12%, purified - 21.05%), hydrogen (crude - 3.4%, purified - 4.13%) and nitrogen (crude - 1.22%, purified - 0.56%) were also analyzed. The anticoagulant activity of the sulfated polysaccharide through APTT and PT was estimated at 14.11 and 8.23IU/mg. The purified polysaccharide with the molecular mass of 20kDa showed highest antioxidant activity (38.57%, 43.48% and 38.88%) in all the assays tested such as DPPH hydroxyl radical, superoxide radical, hydroxyl radical scavenging activities and the structural property was analyzed through FT-IR and (1)H NMR spectrum. The results together suggest that the isolated low molecular weight sulfated polysaccharide will demonstrate as a enormously available alternative natural source of antioxidant for industrial uses. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Manipulating the surface active and anticoagulant properties of heparin through amphiphilic molecular constructs

    Science.gov (United States)

    Mintz, Rosita Candida

    Cardiovascular devices implanted within the vasculature are subjected to non-specific adsorption of plasma proteins. This initiates the blood coagulation cascade and platelet adhesion and activation, leading to thrombus formation. In this thesis Heparin Alkyl Diblock (HAD) surfactants were developed to improve the blood compatibility of cardiovascular biomaterials. The material designs involved using heparin, a natural anticoagulant, to inhibit coagulation pathway enzymes and mimic the cell glycocalyx to provide a repulsive force field to inhibit non-specific protein adsorption. Type AB linear (HAD Cn, n = 6,10,12,18) and branched (HAD nx 18, n = 2,3,4) heparin surfactants were synthesized by end point coupling primary and secondary alkyl amines to heparin via reductive amination. Surfactant yields (83--4%) and anticoagulant activity (149.8 +/- 3.7--39.6 +/- 0.6 IU/mg) decreased with increased branching and hydrocarbon number. Surfactant adsorption, self assembly and molecular packing of HAD surfactants at the air/liquid and liquid/solid interface were a function of the number of hydrocarbons in the surfactant alkyl segment and the presence or absence of an ionic liquid phase. Increased molecular packing was observed at the air/PBS and PBS/graphite interface, relative to aqueous interfaces, resulting from buffer cations shielding heparin's negatively charged sulfate and carboxyl groups. At the PBS/graphite interface, the surfactant's apparent heparin head group cross section decreased in diameter (1.84 to 1.05 nm) and increased in tilt angle (75.7 to 81.9°) with increasing alkyl carbon number (n = 6 to 18). The heparin head group reached a minimum diameter, equivalent to the surfactant's diameter at the air/PBS interface (0.57 nm) just prior to 36 hydrocarbons in the surfactant. For surfactants with 36 to 78 hydrocarbons, the surfactant's heparin head group oriented normal to the graphite surface and alkyl overlap or interdigitation increased (0.02 to 0.59 nm

  13. Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

    Science.gov (United States)

    Blum, Jared; Carreiro, Stephanie; Hack, Jason B

    2013-10-01

    The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237

  14. New orally active anticoagulants in critical care and anesthesia practice: The good, the bad and the ugly

    Directory of Open Access Journals (Sweden)

    Vishal Sehgal

    2013-01-01

    Full Text Available With the adoption of dabigatran, rivaroxaban, and apixaban into clinical practice, a new era has arrived in the practice of oral anticoagulants. Venous thromboembolism (VTE has traditionally been underdiagnosed and under treated in Asia. With increasing longevity, the diagnosis and the need for management of atrial fibrillation (AF and VTE is likely to increase significantly. The new orally active anticoagulants (NOACs have reasonably filled the lacunae that clinicians traditionally faced when treating patients with vitamin K antagonist (VKA. Unlike VKA, NOACs do not need frequent monitoring. Therefore, more patients are likely to get therapeutic effects of anticoagulation and thus reduce morbidity and mortality associated with VTE and AF. However, the clinicians need to be circumspect and exercise caution in use of these medications. In particular (in geriatric population, the clinicians should look out for drug-drug interactions and underlying renal insufficiency. This would ensure therapeutic efficacy and minimize bleeding complications. Here, it is important to note that the antidote for NOACs is not available and is a major concern if emergency surgical procedure is required in their presence.

  15. Coagulation assays and anticoagulant monitoring.

    Science.gov (United States)

    Funk, Dorothy M Adcock

    2012-01-01

    Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

  16. Outpatient management of oral anticoagulation treatment (OAT in general practice: the “Medicina di Gruppo di Masate” experience

    Directory of Open Access Journals (Sweden)

    Fiorenzo Massimo Corti

    2017-04-01

    Full Text Available Outpatient management of oral anticoagulation treatment (OAT in general practice: the “Medicina di Gruppo di Masate” experienceOral anticoagulants are used for prophylaxis in thromboembolic conditions. Vitamin K antagonists (VKAs such as warfarin, are commonly employed. The anticoagulation activity induced by VKAs is monitored by the prothrombin time test to determine the International Normalized Ratio (INR. Point-of-care testing (POCT devices can be used to monitor anticoagulant therapy improving the quality of oral anticoagulation. This paper aims at describing the relevant experience of the “Medicina di Gruppo di Masate” in general practice. We also put this experience into the general context of the international evidence on the impact of POCT. Both our experience and the international evidence may support anticoagulant therapy management by GPs (General Practitioners.

  17. Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature.

    LENUS (Irish Health Repository)

    Alkindi, Salam

    2011-08-01

    Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin-induced thrombocytopenia syndrome (HITS), which develops in about 3-5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7-14 days). Platelet counts decreased to a mean of 38.4 x 10(9) \\/l (12-82 x 10(9)\\/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis.

  18. Effects of L-arginine immobilization on the anticoagulant activity and hemolytic property of polyethylene terephthalate films

    International Nuclear Information System (INIS)

    Liu Yun; Yang Yun; Wu Feng

    2010-01-01

    Surface modification of polyethylene terephthalate (PET) films was performed with L-arginine (L-Arg) to gain an improved anticoagulant surface. The surface chemistry changes of modified films were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The in vitro anticoagulant activities of the surface-modified PET films were evaluated by blood clotting test, hemolytic test, and the measurement of clotting time including plasma recalcification time (PRT), activated partial thromboplastin time (APTT), and prothrombin time (PT). The data of blood coagulation index (BCI) for L-arginine modified PET films (PET-Arg) was larger than that for PET at the same blood-sample contact time. The hemolysis ratio for PET-Arg was less than that for PET and within the accepted standard for biomaterials. The PRT and APTT for PET-Arg were significantly prolonged by 189 s and 25 s, respectively, compared to those for the unmodified PET. All results suggested that the currently described modification method could be a possible candidate to create antithrombogenic PET surfaces which would be useful for further medical applications.

  19. Effects of L-arginine immobilization on the anticoagulant activity and hemolytic property of polyethylene terephthalate films

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yun, E-mail: liuy@tgrc.org [Department of Chemistry, School of Science, Xi' an Jiaotong University, Xi' an 710049 (China); Yang Yun [Department of Chemistry, School of Science, Xi' an Jiaotong University, Xi' an 710049 (China); Wu Feng [Research Centre of Blood, College of Medicine, Xi' an Jiaotong University, Xi' an 710065 (China)

    2010-04-01

    Surface modification of polyethylene terephthalate (PET) films was performed with L-arginine (L-Arg) to gain an improved anticoagulant surface. The surface chemistry changes of modified films were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The in vitro anticoagulant activities of the surface-modified PET films were evaluated by blood clotting test, hemolytic test, and the measurement of clotting time including plasma recalcification time (PRT), activated partial thromboplastin time (APTT), and prothrombin time (PT). The data of blood coagulation index (BCI) for L-arginine modified PET films (PET-Arg) was larger than that for PET at the same blood-sample contact time. The hemolysis ratio for PET-Arg was less than that for PET and within the accepted standard for biomaterials. The PRT and APTT for PET-Arg were significantly prolonged by 189 s and 25 s, respectively, compared to those for the unmodified PET. All results suggested that the currently described modification method could be a possible candidate to create antithrombogenic PET surfaces which would be useful for further medical applications.

  20. Association between Oral Anticoagulation Knowledge ...

    African Journals Online (AJOL)

    Association between Oral Anticoagulation Knowledge, Anticoagulation Control, and Demographic Characteristics of Patients Attending an Anticoagulation Clinic in Saudi Arabia: A Cross-Sectional Prospective Evaluation.

  1. MONITORING OF ANTICOAGULATION IN APROTININ-TREATED PATIENTS DURING HEART OPERATION

    NARCIS (Netherlands)

    TABUCHI, N; NJO, TL; TIGCHELAAR, [No Value; HUYZEN, RJ; BOONSTRA, PW; VANOEVEREN, W

    Since aprotinin has become extensively used during cardiopulmonary bypass the maintenance of safe anticoagulation is a concern. Aprotinin affects anticoagulation measurement by the activated clotting time. Therefore, a reliable new measurement is needed to monitor anticoagulation during

  2. Biological and Biochemical Potential of Sea Snake Venom and Characterization of Phospholipase A2 and Anticoagulation Activity.

    Science.gov (United States)

    Damotharan, Palani; Veeruraj, Anguchamy; Arumugam, Muthuvel; Balasubramanian, Thangavel

    2016-03-01

    This study is designed to isolate and purify a novel anti-clotting protein component from the venom of Enhydrina schistosa, and explore its biochemical and biological activities. The active protein was purified from the venom of E. schistosa by ion-exchange chromatography using DEAE-cellulose. The venom protein was tested by various parameters such as, proteolytic, haemolytic, phospholipase and anti-coagulant activities. 80 % purity was obtained in the final stage of purification and the purity level of venom was revealed as a single protein band of about 44 kDa in SDS-polyacrylamide electrophoresis under reducing conditions. The results showed that the Potent hemolytic activity was observed against cow, goat, chicken and human (A, B and O positive) erythrocytes. Furthermore, the clotting assays showed that the venom of E. schistosa significantly prolonged in activated partial thromboplastin time, thrombin time, and prothrombin time. Venomous enzymes which hydrolyzed casein and gelatin substrate were found in this venom protein. Gelatinolytic activity was optimal at pH 5-9 and (1)H NMR analysis of purified venom was the base line information for the structural determination. These results suggested that the E. schistosa venom holds good promise for the development of novel lead compounds for pharmacological applications in near future.

  3. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

  4. High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis

    NARCIS (Netherlands)

    Lin, Cong; von der Thüsen, Jan; Isermann, Berend; Weiler, Hartmut; van der Poll, Tom; Borensztajn, Keren; Spek, Chris A.

    2016-01-01

    Coagulation activation accompanied by reduced anticoagulant activity is a key characteristic of patients with idiopathic pulmonary fibrosis (IPF). Although the importance of coagulation activation in IPF is well studied, the potential relevance of endogenous anticoagulant activity in IPF progression

  5. Isolation and characterization of anticoagulant compound from ...

    African Journals Online (AJOL)

    GIS

    2013-10-02

    Oct 2, 2013 ... The structural characterization of anticoagulant GAG was analyzed by Fourier transform infrared spectroscopy. Among the marine bivalve, D. faba purified showed more anticoagulant activity than that of crude sample. The results of this study suggest that the GAG from D. faba could be an alternative.

  6. Chemical structure and anticoagulant activity of highly pyruvylated sulfated galactans from tropical green seaweeds of the order Bryopsidales.

    Science.gov (United States)

    Arata, Paula X; Quintana, Irene; Canelón, Dilsia J; Vera, Beatriz E; Compagnone, Reinaldo S; Ciancia, Marina

    2015-05-20

    Sulfated and pyruvylated galactans were isolated from three tropical species of the Bryopsidales, Penicillus capitatus, Udotea flabellum, and Halimeda opuntia. They represent the only important sulfated polysaccharides present in the cell walls of these highly calcified seaweeds of the suborder Halimedineae. Their structural features were studied by chemical analyses and NMR spectroscopy. Their backbone comprises 3-, 6-, and 3,6-linkages, constituted by major amounts of 3-linked 4,6-O-(1'-carboxy)ethylidene-d-galactopyranose units in part sulfated on C-2. Sulfation on C-2 was not found in galactans from other seaweeds of this order. In addition, a complex sulfation pattern, comprising also 4-, 6-, and 4,6-disulfated galactose units was found. A fraction from P. capitatus, F1, showed a moderate anticoagulant activity, evaluated by general coagulation tests and also kinetics of fibrin formation was assayed. Besides, preliminary results suggest that one of the possible mechanisms involved is direct thrombin inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. HEEADSSS assessment for adolescents requiring anticoagulation therapy.

    Science.gov (United States)

    Jones, Sophie; Mertyn, Eliza; Alhucema, Paulina; Monagle, Paul; Newall, Fiona

    2012-05-01

    The care of adolescents with complex chronic illness needs to be developmentally appropriate to encourage adherence, knowledge retention and self-management. There has been an increase in the number of adolescents requiring long-term or lifelong anticoagulation therapy, related to either an underlying illness or idiopathic deep vein thrombosis. The burden of anticoagulant therapy, the associated risks and the required lifestyle changes can significantly impact on psychosocial well-being in the adolescent patient. This review identifies issues pertinent to adolescent anticoagulation management and discusses strategies to support optimal management. The HEEADSSS (Home, Education and employment, Eating, Activities with peers, Drugs, Sexual activity, Suicide and depression, and Safety) framework was used to provide guidance in undertaking a psychosocial assessment of adolescents requiring anticoagulant therapy in conjunction with a structured education strategy. Adolescent anticoagulant management strategies employing developmentally appropriate assessment and education will likely result in improved therapeutic outcomes for the patient and potentially facilitate transition to adult-based care.

  8. A heparin binding synthetic peptide from human HIP / RPL29 fails to specifically differentiate between anticoagulantly active and inactive species of heparin

    Science.gov (United States)

    Hoke, David E; Carson, Daniel D; Höök, Magnus

    2003-01-01

    Despite extensive progress in determining structures within heparin and heparan sulfate (Hp/HS) and the discovery of numerous proteinaceous binding partners for Hp/HS so far; the only detailed characterization of a specific protein-glycosaminoglycan interaction is antithrombin III (ATIII) binding to a Hp pentasaccharide containing a unique 3-O-sulfated glucosamine residue. Previously, it was reported from our laboratories that a 16 amino acid synthetic peptide derived from the C-terminus of human HIP/RPL29 (HIP peptide-1) enriched for ATIII-dependent anticoagulant activity, presumably by specifically binding the ATIII pentasaccharide. Herein, we demonstrate that HIP peptide-1 cannot enrich ATIII-dependent anticoagulant activity from a starting pool of porcine intestinal mucosa Hp through a bio-specific interaction. However, a HIP peptide-1 column can be used to enrich for anticoagulantly active Hp from a diverse pool of glycosaminoglycans known as Hp byproducts by a mechanism of nonspecific charge interactions. Thus, HIP peptide-1 cannot recognize Hp via bio-specific interactions but binds glycosaminoglycans by non-specific charge interactions. PMID:12659638

  9. A rapid pro-hemostatic approach to overcome direct oral anticoagulants.

    Science.gov (United States)

    Thalji, Nabil K; Ivanciu, Lacramioara; Davidson, Robert; Gimotty, Phyllis A; Krishnaswamy, Sriram; Camire, Rodney M

    2016-08-01

    Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that are becoming widely adopted. The ability to reverse their anticoagulant effects is important when serious bleeding occurs or urgent medical procedures are needed. Here, using experimental mouse models of hemostasis, we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence of the anticoagulant effects of these inhibitors. The ability of FXa(I16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability of the active site inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa to persist in plasma. Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis models tested than a noncatalytic antidote that is currently in clinical development. FXa(I16L) also reduces the anticoagulant-associated bleeding in vivo that is induced by the thrombin inhibitor dabigatran. FXa(I16L) may be able to fill an important unmet clinical need for a rapid, pro-hemostatic agent to reverse the effects of several new anticoagulants.

  10. Course of thrombin activation markers in patients implanted with Palmaz-Schatz stents: first experiences with a post-interventional anticoagulation regimen.

    Science.gov (United States)

    Haushofer, A; Halbmayer, W M; Dittel, M; Prachar, H; Mlczoch, J; Fischer, M

    1994-10-01

    Following implantation of coronary Palmaz-Schatz stents, 29 patients were anticoagulated with a combination of heparin, phenprocoumon and aspirin following a standard protocol. After removing the arterial and venous lines, post-interventional intravenous (i.v.) heparin treatment started with 1500 IU/h for patients > 80 kg and 1250 IU/h for patients < 80 kg. Heparin was monitored by the activated partial thromboplastin time (aPTT) and adjusted by increasing or reducing i.v. heparin by 250 IU/h to maintain the aPTT within the therapeutic range. Phenprocoumon therapy began the day after stent implantation (day 2) and lasted for 3 months. aPTT, Heptest, prothrombin fragment F1 and 2 (F1.2) and thrombin-antithrombin III complexes (TAT) were monitored at standard intervals for 10 days (mean monitoring time: 9.7 +/- 2.3 days). Anticoagulation was efficient with aPTT levels remaining within the therapeutic range on day 9 and the simultaneous, moderate-onset oral anticoagulation within the therapeutic range of the International Normalized Ratio (INR; 2.15-4.80) on day 8 on average, the mean INR being 2.43 +/- 0.76. On day 4, F1.2 levels were significantly higher than on the day of stenting (1.16 +/- 0.30 nmol/l vs 1.04 +/- 0.53 nmol/l; P < 0.005). F1.2 levels fell after day 5, the difference becoming significant from day 8 on (P < 0.05). F1.2 was negatively correlated with the Heptest (P < 0.05) and fell significantly as a function of the INR during phenprocoumon administration (P < 0.001). After phenprocoumon therapy was discontinued over 3 weeks, 25 patients were followed up by angiography. Despite adequate anticoagulation, mean F1.2 levels in patients showing restenosis at follow-up angiography were significantly higher (P < 0.005) than in those without restenosis. In one patient who developed subacute stent thrombosis, clotting factors were determined 20 min before stent occlusion. The levels of F1.2 and TAT were less than all other patients on this day (F1.2: 0.98 nmol

  11. [Effect on low-molecular-weight heparin obtained using a chitinolytic complex on the anticoagulant activity of plasma in rabbits and rats].

    Science.gov (United States)

    Drozd, N N; Tolstenkov, A S; Makarov, V A; Miftakhova, N T; Bannikova, G E; Sukhanova, P P; Varlamov, V P; Vikhoreva, G E

    2007-01-01

    The anticoagulant activity of low-molecular-weight heparin with an average molecular weight of 4.7 kD (LMWH-4.7) has been studied. This derivative was prepared from unfractionated heparin with the help of chitinolytic enzyme complex from Streptomyces kurssanovii. The antithrombin activity of LMWH-4.7 (aIla activity) was 72 +/- 9 IU/mg and the activity with respect to the blood coagulation factor Xa (aXa activity) was 200 +/- 33 IU/mg, which corresponded to an aXa/aIIa ratio of 2.8 (necessary for effective antithrombotic drugs). The aIIa and aXa activity exhibited a dose-dependent variation upon intravenous and subcutaneous injections in rabbits, so that a high aIIa/aXa ratio was retained: 5 min after the intravenous injection of a minimum dose (0.3 mg/kg), this ratio was 2, 7, and for a greater dose (3.0 mg/kg) it reached 3.8. Subcutaneous injections were followed by slow elimination of the anticoagulant within 24 h. LMWH-4.7 upon intraperitoneal injections produced a dose-dependent inhibition of a model thrombosis in rats. Complete inhibition was observed for a dose of 3 mg/kg. Thus, it is possible to obtain active LMW heparin with the help of chitinases.

  12. Anti-Inflammatory and Anticoagulative Effects of Paeonol on LPS-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Pin-Kuei Fu

    2012-01-01

    Full Text Available Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS. We established an acute lung injury (ALI model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS. The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI.

  13. Specific antidotes against direct oral anticoagulants: A comprehensive review of clinical trials data.

    Science.gov (United States)

    Tummala, Ramyashree; Kavtaradze, Ana; Gupta, Anjan; Ghosh, Raktim Kumar

    2016-07-01

    The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulation's tests affected, available clinical and preclinical data, and the need for phase III and IV studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Lin, Cong; von der Thüsen, Jan; Isermann, Berend; Weiler, Hartmut; van der Poll, Tom; Borensztajn, Keren; Spek, Chris A

    2016-11-01

    Coagulation activation accompanied by reduced anticoagulant activity is a key characteristic of patients with idiopathic pulmonary fibrosis (IPF). Although the importance of coagulation activation in IPF is well studied, the potential relevance of endogenous anticoagulant activity in IPF progression remains elusive. We assess the importance of the endogenous anticoagulant protein C pathway on disease progression during bleomycin-induced pulmonary fibrosis. Wild-type mice and mice with high endogenous activated protein C APC levels (APC high ) were subjected to bleomycin-induced pulmonary fibrosis. Fibrosis was assesses by hydroxyproline and histochemical analysis. Macrophage recruitment was assessed immunohistochemically. In vitro, macrophage migration was analysed by transwell migration assays. Fourteen days after bleomycin instillation, APC high mice developed pulmonary fibrosis to a similar degree as wild-type mice. Interestingly, Aschcroft scores as well as lung hydroxyproline levels were significantly lower in APC high mice than in wild-type mice on day 28. The reduction in fibrosis in APC high mice was accompanied by reduced macrophage numbers in their lungs and subsequent in vitro experiments showed that APC inhibits thrombin-dependent macrophage migration. Our data suggest that high endogenous APC levels inhibit the progression of bleomycin-induced pulmonary fibrosis and that APC modifies pulmonary fibrosis by limiting thrombin-dependent macrophage recruitment. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Anticoagulant effect of marine algae.

    Science.gov (United States)

    Kim, Se-Kwon; Wijesekara, Isuru

    2011-01-01

    Recently, a great deal of interest has been developed in the nutraceutical and pharmaceutical industries to isolate natural anticoagulant compounds from marine resources. Among marine resources, marine algae are valuable sources of novel bioactive compounds with anticoagulant effect. Phlorotannins and sulfated polysaccharides such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae have been recognized as potential anticoagulant agents. Therefore, marine algae-derived phlorotannins and SPs have great potential for developing as anticoagulant drugs in nutraceutical and pharmaceutical areas. This chapter focuses on the potential anticoagulant agents in marine algae and presents an overview of their anticoagulant effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Anticoagulant activity of sulfated polysaccharides fractions from an aqueous extract obtained from the red seaweed Halymenia floresia (Clemente C. Agardh - doi: 10.4025/actascitechnol.v33i4.9143

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2011-09-01

    Full Text Available Heparin (HEP is known due to their side effects and the red seaweed Halymenia floresia (Hf sulfated polysaccharides (SP are heparinoids. In this study we purified the Hf-SP obtained from an aqueous extract and evaluated their anticoagulant activities. Hf-SP1 (25°C, Hf-SP2 (80°C and Hf-SP3 (80°C were sequentially isolated. Hf-SP3 had the highest sulfate content (37.45%. Hf-SP3 was fractionated by ion exchange chromatography on a DEAE-cellulose column using a NaCl gradient. Fractions were lyophilized and submitted to 0.5% agarose gel electrophoresis. The anticoagulant activity was evaluated by the activated partial thromboplastin time using rabbits plasma and expressed in international units per mg of SP using standard HEP (193 IU mg-1. The chromatographic procedure separated into four different SP fractions (F I, F II, F III and F IV eluted at concentrations of 0.50, 0.75, 1.00 and 1.25 M of NaCl, respectively, reveling among them different marked on charge density, when compared by electrophoresis. F III had the highest anticoagulant activity (10.72 IU mg-1, suggesting that the sulfate is important in this process. In conclusion, our results suggest that sequential extractions of Hf-SP are an important biotechnological tool for identification of novel anticoagulants and studies of structural characterization are already in progress.

  17. [Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex(TAT) and thrombophilia parameters in orally anticoagulated patients with inferior vena cava filters].

    Science.gov (United States)

    Halbmayer, W M; Haushofer, A; Toth, E

    1993-01-01

    Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III-complex (TAT) levels were compared in 31 orally anticoagulated patients with inferior vena caval filters and a control group of 31 orally anticoagulated patients without caval filters and the incidence of markers of thrombophilia (deficiency of antithrombin-III, protein C, protein S and factor XII, presence of lupus anticoagulants) was determined. 8 of 31 patients (26%) from the group of caval filter carriers showed markers of thrombophilia (3 protein S deficiencies, 1 protein C deficiency, 2 factor XII deficiencies and 2 patients with lupus anticoagulants). In all orally anticoagulated patients a significant interdependence (p < 0.05) between F1 + 2- and TAT-levels and intensity (INR) of the oral anticoagulation could be observed. Comparison of F1 + 2- and TAT-levels of caval filter carriers and controls revealed no significant difference which leads to the conclusion that inferior vena caval filters do not induce detectable systemic activation of prothrombin under adequate oral anticoagulation therapy.

  18. ["Lupus anticoagulant" in immune hyperthyroidism].

    Science.gov (United States)

    Schuler, G; Alexopoulos, A; Hasler, K; Kerp, L

    1990-10-05

    A 56-year-old woman with autoimmune hyperthyroidism (Basedow) whose blood coagulation had at first been normal developed prolonged partial thromboplastin time (PTT) of 48 s and a fall in prothrombin time (Quick value) to 52%. At the same time, total activity of factor VIII was reduced to 18% and factor IX to 16%. These values not having changed after the addition of normal plasma, it is assumed that an acquired inhibitor of plasmatic coagulation was responsible. Such inhibitors were first described in lupus erythematodes and therefore called lupus anticoagulant, but later also demonstrated in other autoimmune diseases.

  19. Anticoagulant effects of an antidiabetic drug on monocytes in vitro.

    Science.gov (United States)

    Henriksson, C E; Hellum, M; Haug, K B F; Aass, H C; Joø, G B; Øvstebø, R; Trøseid, A M; Klingenberg, O; Kierulf, P

    2011-11-01

    Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties. We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry). Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs. Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. [A new deal with new anticoagulants?].

    Science.gov (United States)

    Godier, A; Samama, C-M

    2010-06-01

    The anticoagulant market has been very active recently with the development of new compounds including injectable anti-Xa such as fondaparinux, already available, and idraparinux, already replaced by its new biotynilateed form, and new oral drugs which can be divided into anti-IIa with dabigatran already available, and anti-Xa, such as the recently marketed rivaroxaban and apixaban still in the development stage. Others are coming forward. The competition is strong and the place for each drug remains to be determined. This review discusses these new anticoagulants in terms of efficacy and tolerance based on data in the literature. These recent reports mainly concern prophylaxis for orthopedic surgery but also consider treatment of deep venous thrombosis. The results of studies in heart patients have raised much curiosity since they will be determinant in the future use of innovating compounds, which could replace current oral anticoagulants. This will be upcoming but not yet for tomorrow.

  1. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

  2. Anticoagulant property of sulphated polysaccharides extracted from ...

    African Journals Online (AJOL)

    The marine brown algae: Sargassum tenerrimum, Sargassum wightii, Turbinaria conoides, Turbinaria ornata and Padina tetrastromatica were collected from Mandapam Island, India. The crude sulphated polysaccharides (SPS) were extracted using hot water and examined for anticoagulation activity. The sugar, sulphate ...

  3. Isolamento, fracionamento e atividade anticoagulante de iota-carragenanas da Solieria filiformis Isolation, fractionation and anticoagulant activity of iota-carrageenans from Solieria filiformis

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2010-11-01

    Full Text Available Este estudo teve como objetivo isolar, fracionar e avaliar o potencial anticoagulante de iota-carragenanas (i-CARs da rodofícea Solieria filiformis, quando obtidas por dois métodos de extração (M I e M II. As i-CARs foram isoladas com papaína bruta em tampão acetato de sódio 0,1M (pH 5,0, contendo cisteína 5mM e EDTA 5mM (M I ou água (80°C (M II e, em seguida, determinada sua composição química de carboidratos totais, sulfato livre (SL e proteínas contaminantes. As i-CARs foram submetidas à cromatografia de troca iônica (DEAE-celulose usando um gradiente de cloreto de sódio, sendo avaliado o tempo de tromboplastina parcial ativada (TTPA e tempo de protrombina das frações obtidas e comparadas à heparina (193UI mg-1. Uma fração anticoagulante também foi submetida ao procedimento de eletroforese em gel de agarose a 0,5%. A diferença no rendimento de i-CARs entre os métodos foi 10,14%. A composição química de SL (29,40% e o fracionamento, por DEAE-celulose, indicaram o M I mais eficiente na obtenção de i-CARs, comparado ao M II. O TTPA também foi somente alterado para as i-CARs do M I. Contudo, a atividade anticoagulante in vitro de uma fração rica (8,52UI mg-1 foi inferior à da heparina.This study aimed to isolate, fractionate and evaluate the anticoagulant potential of iota-carrageenans (i-CARs from Solieria filiformis when two extraction methods (M I and M II were used. i-CARs were isolated with papain in 0.1M sodium acetate (pH 5.0 containing 5mM cystein and 5mM EDTA (M I or water (80°C (M II, and then their chemical composition of total carbohydrates, free sulfate (FS and contaminant proteins were determined. i-CARs were submitted to anion-exchange chromatography (DEAE-cellulose using a sodium chloride gradient,being evaluated the activated partial thromboplastin time (APTT and prothrombin time of obtained fractions and compared to heparin (193IU mg-1. A rich fraction of anticoagulant was also submitted to 0

  4. The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects.

    Science.gov (United States)

    Halbmayer, W M; Haushofer, A; Schön, R; Fischer, M

    1994-02-01

    A poor anticoagulant response to activated protein C (APC) in an activated partial thromboplastin time (aPTT) assay (APC resistance) was recently reported to be a cause of familial thrombophilia. The response to APC was measured in 30 patients suffering from juvenile or recurrent stroke, in 40 patients suffering from venous thromboembolism and in 50 healthy subjects. The prevalence of APC resistance was found to be significantly higher among patients with stroke (20%, P < 0.003) and venous thrombosis (17.5%, P < 0.02) compared with the prevalence of APC resistance among normal controls (2%). In one case of venous thrombosis, the proposita's family (A) could be investigated and in five out of nine investigated members (56%) a poor or borderline response to APC was detected. The family (B) of another APC-resistant patient revealed six subjects with poor coagulation response to APC out of eight family members studied (75%). Measuring protein S activity with an automated calcium-thromboplastin-based protein S activity assay, a significant correlation (P < 0.0001) between the results of this functional protein S assay and APC resistance (represented by the ratio (Rs value) of clotting time with and without addition of activated protein C) was observed. Nine out of 14 patients (64%) with poor APC response showed protein S activities below the normal range. Assessment of protein S activity with a second protein S clotting assay using factor Va as substrate confirmed only 47% of the decreased levels of the thromboplastin-based protein S clotting assay.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Roll-to-roll, shrink-induced superhydrophobic surfaces for antibacterial applications, enhanced point-of-care detection, and blood anticoagulation

    Science.gov (United States)

    Nokes, Jolie McLane

    Superhydrophobic (SH) surfaces are desirable because of their unique anti-wetting behavior. Fluid prefers to bead up (contact angle >150°) and roll off (contact angle hysteresis micro- and nanostructure features trap air pockets. Fluid only adheres to the peaks of the structures, causing minimal adhesion to the surface. Here, shrink-induced SH plastics are fabricated for a plethora of applications, including antibacterial applications, enhanced point-of-care (POC) detection, and reduced blood coagulation. Additionally, these purely structural SH surfaces are achieved in a roll-to-roll (R2R) platform for scalable manufacturing. Because their self-cleaning and water resistant properties, structurally modified SH surfaces prohibit bacterial growth and obviate bacterial chemical resistance. Antibacterial properties are demonstrated in a variety of SH plastics by preventing gram-negative Escherichia coli (E. coli) bacterial growth >150x compared to flat when fluid is rinsed and >20x without rinsing. Therefore, a robust and stable means to prevent bacteria growth is possible. Next, protein in urine is detected using a simple colorimetric output by evaporating droplets on a SH surface. Contrary to evaporation on a flat surface, evaporation on a SH surface allows fluid to dramatically concentrate because the weak adhesion constantly decreases the footprint area. On a SH surface, molecules in solution are confined to a footprint area 8.5x smaller than the original. By concentrating molecules, greater than 160x improvements in detection sensitivity are achieved compared to controls. Utility is demonstrated by detecting protein in urine in the pre-eclampsia range (150-300microgmL -1) for pregnant women. Further, SH surfaces repel bodily fluids including blood, urine, and saliva. Importantly, the surfaces minimize blood adhesion, leading to reduced blood coagulation without the need for anticoagulants. SH surfaces have >4200x and >28x reduction of blood residue area and

  6. New Trends in Anticoagulation Therapy.

    Science.gov (United States)

    Smith, Margaret; Wakam, Glenn; Wakefield, Thomas; Obi, Andrea

    2018-04-01

    Anticoagulation pharmacy has been dramatically altered with US Food and Drug Administration (FDA) approval of 5 direct oral anticoagulants, 1 novel reversal agent and, a second designated for fast-track approval. Trial data surrounding current trends in anticoagulant choice for VTE, reversal, and bridging are constantly redefining practice. Extended therapy for unprovoked VTE has expanded to include low-dose direct oral anticoagulants, aspirin, and the use of the HERDOO2 system to identify women who can stop anticoagulant therapy without increased risk of recurrent VTE. Trends in thromboprophylaxis include extended duration low-dose direct oral anticoagulants to prevent VTE in high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Chronic kidney disease and anticoagulation

    DEFF Research Database (Denmark)

    Sciascia, Savino; Radin, Massimo; Schreiber, Karen

    2017-01-01

    Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight...... are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin...

  8. Direct oral anticoagulants: An update.

    Science.gov (United States)

    Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

    2017-12-30

    Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  9. Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride on Anticoagulant Activity of Guinea Pig Plasma.

    Science.gov (United States)

    Drozd, N N; Shagdarova, B Ts; Il'ina, A V; Varlamov, V P

    2017-07-01

    Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.

  10. Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.

    Science.gov (United States)

    Ebner, Matthias; Birschmann, Ingvild; Peter, Andreas; Härtig, Florian; Spencer, Charlotte; Kuhn, Joachim; Blumenstock, Gunnar; Zuern, Christine S; Ziemann, Ulf; Poli, Sven

    2017-09-01

    In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations 95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070. © 2017 American Heart Association, Inc.

  11. Antiplatelet and Anticoagulant Drugs in Interventional Radiology

    International Nuclear Information System (INIS)

    Altenburg, Alexander; Haage, Patrick

    2012-01-01

    In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

  12. Anticoagulation Considerations for Travel to High Altitude.

    Science.gov (United States)

    DeLoughery, Thomas G

    2015-09-01

    DeLoughery, Thomas G. Anticoagulation considerations for travel to high altitude. High Alt Med Biol 16:181-185, 2015.-An increasing percentage of the population are on anticoagulation medicine for clinical reasons ranging from stroke prevention in atrial fibrillation to long term prevention of deep venous thrombosis. In recent years, several new direct oral anticoagulants have entered the market. The key questions that should be kept in mind when approaching a potential traveler on anticoagulation are: 1) why is the patient on anticoagulation? 2) do they need to stay on anticoagulation? 3) what are the choices for their anticoagulation? 4) will there be any drug interactions with medications needed for travel? and 5) how will they monitor their anticoagulation while traveling? Knowing the answers to these questions then can allow for proper counseling and planning for the anticoagulated traveler's trip.

  13. Management of refractory bleeding post-cardiopulmonary bypass in an acute heparin-induced thrombocytopenia type II renal failure patient who underwent urgent cardiac surgery with bivalirudin (Angiox®) anticoagulation.

    Science.gov (United States)

    Hassen, Kimberly; Maccaroni, Maria R; Sabry, Haytham; Mukherjee, Smitangshu; Serumadar, Shankari; Birdi, Inderpaul

    2018-04-01

    Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

  14. Avaliação do desempenho dos reagentes do tempo de tromboplastina parcial ativada utilizados para detectar o anticoagulante lúpico Assessment of the performance of reagents of activated partial thromboplastin time used to detect the lupus anticoagulant

    Directory of Open Access Journals (Sweden)

    Fernanda Chiuso

    2005-06-01

    Full Text Available INTRODUÇÃO: O anticoagulante lúpico é uma imunoglobulina pertencente à família dos anticorpos antifosfolípides. A sua ação in vitro é interferir nos testes de coagulação dependentes de fosfolípides. O tempo de tromboplastina parcial ativada (TTPA é um teste utilizado como screening na pesquisa do anticoagulante lúpico. Os reagentes utilizados neste teste apresentam grandes variações quanto à sensibilidade. OBJETIVO: Avaliar o desempenho dos reagentes do TTPA e detectar a presença do anticoagulante lúpico através de diferentes testes da coagulação. MATERIAL E MÉTODO: A pesquisa do anticoagulante lúpico foi realizada em 50 amostras plasmáticas de pacientes do sexo feminino através dos testes do TTPA, do tempo de coagulação do caulim (TCC, do tempo de tromboplastina parcial ativada diluída (TTPAd e do tempo do veneno da víbora de Russel diluído (TVVRd. Três cefalinas comerciais foram avaliadas pelos testes do TTPA e do TTPAd. Na comparação entre os reagentes estudados foi aplicado o cálculo do intervalo de confiança (95%. RESULTADOS: Os três reagentes avaliados apresentaram boa concordância e os métodos utilizados responderam bem à pesquisa do anticoagulante lúpico. DISCUSSÃO E CONCLUSÃO: As três cefalinas comerciais avaliadas podem ser utilizadas na rotina laboratorial para a pesquisa do anticoagulante lúpico.INTRODUCTION: The lupus anticoagulant is an immunoglobin which belongs to the antiphospholid antibodies family. Its in vitro function is to interfere with coagulation tests that are dependent on phospholipids. The activated partial thromboplastin time (APTT is a test used as screening on lupus anticoagulant research. Reagents used in this test demonstrate wide sensitivity ranges. OBJECTIVE: To assess the performance of APTT reagents and detect the presence of lupus anticoagulant through various coagulation tests. MATERIAL AND METHOD: The lupus anticoagulant research was performed in plasma from 50

  15. Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art.

    Science.gov (United States)

    Iapichino, Giacomo E; Bianchi, Paolo; Ranucci, Marco; Baryshnikova, Ekaterina

    2017-06-01

    Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. New developments in parenteral anticoagulation for arterial and venous thromboembolism

    NARCIS (Netherlands)

    van Es, Nick; Bleker, Suzanne M.; Büller, Harry R.; Coppens, Michiel

    2013-01-01

    The efficacy and safety of heparin and low-molecular-weight heparins (LMWHs) are well documented in venous and arterial thromboembolism. Several drawbacks of heparins have inspired the development of newer parenteral anticoagulants for specific indications, including heparin-induced thrombocytopenia

  17. Safety and tolerability of a modified filter-type device for leukocytapheresis using ACD-A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study.

    Science.gov (United States)

    Muratov, Vladislaw; Lundahl, Joachim; Mandic-Havelka, Aleksandra; Elvin, Kerstin; Ost, Ake; Shizume, Yasumasa; Furuya, Kaoru; Löfberg, Robert

    2010-01-01

    Cellsorba™ is a medical device for leukocytapheresis (LCAP) treatment of ulcerative colitis (UC). Cellsorba™ EX Global type has been developed from Cellsorba E for intended use with ACD-A as anticoagulant. We evaluated safety and efficacy of the modified Cellsorba using ACD-A in a pilot trial comprising patients with active UC, despite receiving 5-ASA. A total of 10 LCAP treatments/patients were administered. Safety assessment focused on clinical signs and symptoms, hematological variables, as well as levels of bradykinin and IL-6. Efficacy was determined using the Mayo clinical/endoscopic scoring index as well histological assessment of biopsies. Additional aim was to evaluate the impact of apheresis system lines and filter on selected regulatory molecules. All six subjects completed the trial without any serious adverse events. WBC, platelet counts, and levels of bradykinin and IL-6 were not significantly affected. The median Mayo score decreased from 8.0 to 3.5 at week 8 (and to 2 at week 16 for the responders). Four patients were responders, of whom two patients went into remission. Median histological scores decreased from 3.5 to 2.0 in these four patients. Concentration of LL-37 increased within the apheresis system lines. LCAP with Cellsorba EX using ACD-A as anticoagulant was found to be a safe and well-tolerated procedure in patients with active UC. The positive impact on efficacy parameters merits further evaluation in a controlled fashion.

  18. Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

    Science.gov (United States)

    György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I

    2014-02-01

    Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope.

    Science.gov (United States)

    Lian, Wu; Wu, Mingyi; Huang, Ning; Gao, Na; Xiao, Chuang; Li, Zi; Zhang, Zhigang; Zheng, Yongtang; Peng, Wenlie; Zhao, Jinhua

    2013-10-01

    Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure-activity relationships (SAR) of FG for combating HIV-1 infection. Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5-12.8kDa), might display high anti-HIV-1 activity and low anticoagulant activity. Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Efficiency of three anti-coagulant rodenticides on commensal rodents.

    Science.gov (United States)

    Mikhail, M W; Kamilia; Allam, A M; Soliman, M I

    2007-08-01

    Susceptibiliy level to bromadilone, difencoum and coumtertraly anticoagulants were studied in different species of Norway rat Rattus norvegicus and roof rat Rattus rattus trapped from El-Qualyobia Governorate in which the anticoagulant rodenticides were used to control rodents for long periods in some rural regions at Qualyobia. Complete mortality was showed for both species and sex within a standard feeding period (6 days) indicated to be susceptible to the three anticoagulant rodenticides. The bait eaten and corresponding active ingredient showed a noticeable more intake for R. rattus than R. norvegicus for the three compounds. The time to death showed highest mean values for R. rattus comparison to R. norvegicus. Difencoum recorded highest values of time to death compare with bromadilone and coumatetralyl.

  1. Anticoagulants Influence the Performance of In Vitro Assays Intended for Characterization of Nanotechnology-Based Formulations.

    Science.gov (United States)

    Cedrone, Edward; Neun, Barry W; Rodriguez, Jamie; Vermilya, Alison; Clogston, Jeffrey D; McNeil, Scott E; Barenholz, Yechezkel; Szebeni, Janos; Dobrovolskaia, Marina A

    2017-12-21

    The preclinical safety assessment of novel nanotechnology-based drug products frequently relies on in vitro assays, especially during the early stages of product development, due to the limited quantities of nanomaterials available for such studies. The majority of immunological tests require donor blood. To enable such tests one has to prevent the blood from coagulating, which is usually achieved by the addition of an anticoagulant into blood collection tubes. Heparin, ethylene diamine tetraacetic acid (EDTA), and citrate are the most commonly used anticoagulants. Novel anticoagulants such as hirudin are also available but are not broadly used. Despite the notion that certain anticoagulants may influence assay performance, a systematic comparison between traditional and novel anticoagulants in the in vitro assays intended for immunological characterization of nanotechnology-based formulations is currently not available. We compared hirudin-anticoagulated blood with its traditional counterparts in the standardized immunological assay cascade, and found that the type of anticoagulant did not influence the performance of the hemolysis assay. However, hirudin was more optimal for the complement activation and leukocyte proliferation assays, while traditional anticoagulants citrate and heparin were more appropriate for the coagulation and cytokine secretion assays. The results also suggest that traditional immunological controls such as lipopolysaccharide (LPS ) are not reliable for understanding the role of anticoagulant in the assay performance. We observed differences in the test results between hirudin and traditional anticoagulant-prepared blood for nanomaterials at the time when no such effects were seen with traditional controls. It is, therefore, important to recognize the advantages and limitations of each anticoagulant and consider individual nanoparticles on a case-by-case basis.

  2. Anticoagulants Influence the Performance of In Vitro Assays Intended for Characterization of Nanotechnology-Based Formulations

    Directory of Open Access Journals (Sweden)

    Edward Cedrone

    2017-12-01

    Full Text Available The preclinical safety assessment of novel nanotechnology-based drug products frequently relies on in vitro assays, especially during the early stages of product development, due to the limited quantities of nanomaterials available for such studies. The majority of immunological tests require donor blood. To enable such tests one has to prevent the blood from coagulating, which is usually achieved by the addition of an anticoagulant into blood collection tubes. Heparin, ethylene diamine tetraacetic acid (EDTA, and citrate are the most commonly used anticoagulants. Novel anticoagulants such as hirudin are also available but are not broadly used. Despite the notion that certain anticoagulants may influence assay performance, a systematic comparison between traditional and novel anticoagulants in the in vitro assays intended for immunological characterization of nanotechnology-based formulations is currently not available. We compared hirudin-anticoagulated blood with its traditional counterparts in the standardized immunological assay cascade, and found that the type of anticoagulant did not influence the performance of the hemolysis assay. However, hirudin was more optimal for the complement activation and leukocyte proliferation assays, while traditional anticoagulants citrate and heparin were more appropriate for the coagulation and cytokine secretion assays. The results also suggest that traditional immunological controls such as lipopolysaccharide (LPS are not reliable for understanding the role of anticoagulant in the assay performance. We observed differences in the test results between hirudin and traditional anticoagulant-prepared blood for nanomaterials at the time when no such effects were seen with traditional controls. It is, therefore, important to recognize the advantages and limitations of each anticoagulant and consider individual nanoparticles on a case-by-case basis.

  3. Emergency management of major bleeding in a case of maxillofacial trauma and anticoagulation: utility of prothrombin complex concentrates in the shock room

    Directory of Open Access Journals (Sweden)

    Alessandro Morotti

    2015-03-01

    Full Text Available Life-threatening bleeding in anticoagulation with Warfarin is an emergency challenging issue. Several approaches are available to treat bleeding in either over-anticoagulation or propeanticoagulation, including vitamin K, fresh frozen plasma and prothrombin complex concentrates (PCC administration. In coexisting trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be a rapid and highly effective procedure. Furthermore the appropriate treatment must be directly available in each shock rooms to guarantee the rapid management of the emergency. PCC require a simple storage, rapid accessibility, fast administration procedures and high effectiveness. Here we report the utility of PCC in management of a craniofacial trauma in proper-anticoagulation.

  4. Transitions of care in anticoagulated patients

    Directory of Open Access Journals (Sweden)

    Michota F

    2013-06-01

    Full Text Available Franklin Michota Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA Abstract: Anticoagulation is an effective therapeutic means of reducing thrombotic risk in patients with various conditions, including atrial fibrillation, mechanical heart valves, and major surgery. By its nature, anticoagulation increases the risk of bleeding; this risk is particularly high during transitions of care. Established anticoagulants are not ideal, due to requirements for parenteral administration, narrow therapeutic indices, and/or a need for frequent therapeutic monitoring. The development of effective oral anticoagulants that are administered as a fixed dose, have low potential for drug-drug and drug-food interactions, do not require regular anticoagulation monitoring, and are suitable for both inpatient and outpatient use is to be welcomed. Three new oral anticoagulants, the direct thrombin inhibitor, dabigatran etexilate, and the factor Xa inhibitors, rivaroxaban and apixaban, have been approved in the US for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; rivaroxaban is also approved for prophylaxis and treatment of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery. This review examines current options for anticoagulant therapy, with a focus on maintaining efficacy and safety during transitions of care. The characteristics of dabigatran etexilate, rivaroxaban, and apixaban are discussed in the context of traditional anticoagulant therapy. Keywords: hemorrhagic events, oral anticoagulation, parenteral anticoagulation, stroke, transitions of care

  5. Oral anticoagulation in primary care.

    Science.gov (United States)

    Altirriba, J; Aparicio, P

    2017-06-01

    Oral anticoagulant therapy is currently widespread in the population and primary care plays an important role in its control in Spain. Younger populations, such as those in prisons, often require this treatment for reasons other than atrial fibrillation, often in relation to valvular or congenital or acquired hypercoagulability situations. The possibility of obtaining the INR by portable coagulometers has allowed primary care physicians to tackle the indication of this therapy and the control of these patients in coordination with haematology services. The emergence of new therapeutic alternatives (Dabigatran, Rivaroxaban, Apixaban and Edoxaban, the so called "ACOD") has permitted the expansion of options for oral anticoagulation in some cases, since they do not require systematic monitoring of their effect and interact with far fewer drugs than their predecessors, although there are still restrictions by the health authorities on their widespread use. This article reviews the different indications of oral anticoagulant therapy according to the new recommendations as well as the clinical scenarios in which it should be used.

  6. Anticoagulant rodenticides and wildlife: Introduction

    Science.gov (United States)

    van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

    2018-01-01

    Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

  7. Distribution of induced activity in tungsten targets

    International Nuclear Information System (INIS)

    Donahue, R.J.; Nelson, W.R.

    1988-09-01

    Estimates are made of the induced activity created during high-energy electron showers in tungsten, using the EGS4 code. Photon track lengths, neutron yields and spatial profiles of the induced activity are presented. 8 refs., 9 figs., 1 tab

  8. The interaction between anticoagulant protein S and complement regulatory C4b-binding protein (C4BP)

    NARCIS (Netherlands)

    van de Poel, R. H.; Meijers, J. C.; Bouma, B. N.

    2000-01-01

    An important mechanism of regulation of blood coagulation is the anticoagulant protein C pathway. In this pathway, the anticoagulant activity of activated protein C is increased by its cofactor protein S. The cofactor activity of protein S can be regulated by binding to complement regulatory

  9. Compatibility of Injectable Anticoagulant Agents in Ethanol; In Vitro Antibiofilm Activity and Impact on Polyurethane Catheters of Enoxaparin 400 U/mL in 40% v/v Ethanol.

    Science.gov (United States)

    Balestrino, Damien; Quintana, Mercédès; Charbonnel, Nicolas; Forestier, Christiane; Lartigue, Claire; Souweine, Bertrand

    2016-01-01

    Interdialytic lock solutions should maintain catheter patency and prevent catheter infections. We aimed to determine in which conditions injectable anticoagulant agents (IAAs) combined with ethanol are compatible and to assess the antibiofilm activity of the selected combination and its effects on dialysis catheters (DC). The solubility and compatibility of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), heparinoids and fondaparinux (50 to 2,500 U/mL) in 30 to 70% ethanol were determined by visual observation. The stability of enoxaparin in ethanol and the ethanol content were assessed by high performance liquid chromatography (HPLC) and titrimetric control, respectively. The bactericidal effect was determined on 24h-old biofilms embedded in silicone-DC. The integrity of polyurethane-DC immersed in anticoagulant-ethanol was assessed by gas chromatography-mass spectrometry (GC-MS) and compared with previously published results. The compatibility of IAAs and ethanol varied according to IAA type and concentration, and ethanol content. UFH in 40% ethanol was not compatible, whatever the UFH concentration used. Established limits of compatibility of enoxaparin, nadroparin, dalteparin and tinzaparin in 40% ethanol were 1350, 575, 307 and 207 U/ml, respectively, and up to 300 U/ml for danaparoid and 1 mg/mL for fondaparinux. Enoxaparin 400 U/mL in 40% ethanol (Enox/Eth) eradicated biofilm after 4 hours of exposure for Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans and after 24 hours for Klebsiella pneumoniae and S. aureus. Aliphatic carbonate and alcohol compounds were released by polyurethane-DC after Enox/Eth exposure, as after 40% ethanol or saline exposure. There was no significant difference between the amounts released after 30 minutes of exposure to Enox/Eth and 15 days to saline. A 40% ethanol solution can be combined with all IAAs but UFH. Enox/Eth was effective as an anti-biofilm agent with minor impacts on DC

  10. Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper

    NARCIS (Netherlands)

    Ageno, Walter; Büller, Harry R.; Falanga, Anna; Hacke, Werner; Hendriks, Jeroen; Lobban, Trudie; Merino, Jose; Milojevic, Ivan S.; Moya, Francisco; van der Worp, H. Bart; Randall, Gary; Tsioufis, Konstantinos; Verhamme, Peter; Camm, A. John

    2016-01-01

    Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies

  11. New oral anticoagulants: key messages for clinicians

    Directory of Open Access Journals (Sweden)

    Matteo Giorgi-Pierfranceschi

    2013-12-01

    Full Text Available New oral anticoagulants are an effective and safe alternative to vitamin K antagonists in many fields of clinical practice. The use of the direct inhibitors of activated Factor II (dabigatran and activated Factor X (apixaban and rivaroxaban, both in patients with non-valvular atrial fibrillation (NVAF and those with acute venous thromboembolism (VTE, is of great interest for internal medicine physicians. This paper aims to give practical guidance on management (starting therapy, follow up and bleeding complications of patients treated with dabigatran, rivaroxaban or apixaban for NVAF or acute VTE providing practical tables concerning the phases of therapy, management of complications, drug interaction and dose adjustment if renal impairment occurs.

  12. Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Ashis K Mukherjee

    Full Text Available The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia.By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation.In order to develop peptide-based superior anticoagulant therapeutics, future application of Nk-PLA2

  13. Direct oral anticoagulants and venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Massimo Franchini

    2016-09-01

    Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

  14. Optical sensing of anticoagulation status: Towards point-of-care coagulation testing.

    Directory of Open Access Journals (Sweden)

    Diane M Tshikudi

    Full Text Available Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle and maximum clot stiffness (MA were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG. To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57-0.77, p<0.04 and all LSR parameters demonstrated good correlation with TEG (r = 0.61-0.87, p<0.04. To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01. LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01. Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.

  15. Chemotherapy induces enhanced procoagulant activity through phosphatidylserine exposure in acute lymphoblastic leukemia.

    Science.gov (United States)

    Dong, Xiushuai; Shi, Jialan; Zhou, Jin; Chen, Xi; Jin, Yinglan; Zhang, Xiaomin; Li, Xiaoyun; Dai, Haibin; Wang, Jinghua

    2013-11-01

    Thromboembolism is a serious complication in patients with acute lymphoblastic leukemia (ALL). Coagulation disorders can be induced and worsened by cytotoxic drugs; however, the mechanisms are largely unknown. Our study aims to investigate the effects of daunorubicin (DNR) and L-asparaginase (L-ASP) on phosphatidylserine (PS) exposure and the procoagulant activity (PCA) of Jurkat/ALL cells. The anticoagulant properties of lactadherin were also explored. Jurkat cells and cells from 10 newly diagnosed patients with ALL were treated with DNR or L-ASP. Flow cytometry and confocal microscopy were used to quantify and locate PS exposure, respectively. PCA was evaluated using coagulation assays and purified coagulation complex assays. Lactadherin, a glycoprotein of the milk fat globule membrane with stereospecific binding to phosphatidyl-L-serine, was used as a probe for the detection of exposed PS. Untreated Jurkat/ALL cells exhibited higher PS exposure and greater PCA than mononuclear cells (MNCs). The PCA of cells treated with DNR or L-ASP was markedly increased. Flow cytometry and confocal microscopy indicated that the increased PCA occurred in parallel with PS exposure. The blocking of PS with lactadherin prolonged the coagulation time and inhibited approximately 85-90% of the activities of procoagulant enzyme complexes in Jurkat/ALL cells. Our results indicate that DNR and L-ASP increased the PCA of Jurkat/ALL cells through PS exposure and played a critical role in inducing thrombosis in ALL patients. Lactadherin is an ideal probe for PS detection at an early stage and a potential anticoagulant to improve the hypercoagulability of ALL patients. © 2013.

  16. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  17. THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS

    Science.gov (United States)

    Broome, J. D.; Kidd, John G.

    1964-01-01

    Experiments given in this paper have shown that 4-arsonophenylazoproteins possess marked anticoagulant activity both in vivo and in vitro. Mice and rabbits given moderate amounts of the arsenic azoprotein, for example, often bled to death from injuries that proved trivial in control animals, and their blood remained liquid during many hours' postmortem even when left in contact with transected tissues, fibrinolysis having no part in the outcome. So, too, the addition of minute amounts of 4-arsonophenylazoprotein to plasma procured from citrated rabbit or human blood greatly prolonged the time required for clotting after recalcification. Other arsenic-containing compounds,—for example, those in which arsenic See PDF for Structure was joined to amino acids or peptides through the azo linkage, or to proteins through couplings other than the azo linkage,—were largely devoid of anticoagulant and antilymphoma effects. The findings as a whole show clearly that the structural requirements for anticoagulant and antilymphoma effects are: (a) possession of negatively charged arsonic or arsinoso groups, (b) large molecular size (protein), and (c) linkage of arsenic-containing groups to protein through the azo bond. Two acidic azoproteins that were devoid of arsenic,—namely 4-carboxyphenylazoprotein and 4-sulfonophenylazoprotein,—were also found to have marked anticoagulant effects in vitro, but they had no inhibitory action against cells of Lymphoma 6C3HED in vivo, even when they were given to mice in maximum tolerated amounts. The essential part played by arsenic in the antilymphoma activity of arsenic azoproteins was further emphasized by the action of dimercaprol (BAL) in preventing the antilymphoma effects of 4-arsonophenylazoprotein on Lymphoma 6C3HED cells in vivo. In an associated paper the anticoagulant and antilymphoma effects of 4-arsonophenylazoproteins are studied further, and consideration is given to the ways in which these effects may be brought about

  18. Anticoagulant Control Results among Patients with Mechanical ...

    African Journals Online (AJOL)

    Background: Patients with mechanical heart valves receive life long, oral anticoagulant therapy to prevent thromboembolic complications, but this treatment is associated with an increased risk of bleeding (1). However no study in Tanzania has been done to review the adequacy of anticoagulation monitoring and risk factors ...

  19. Anticoagulation

    Science.gov (United States)

    ... be hazardous. These medicines include most antibiotics, several pain medicines (e.g., non-steroidal anti-inflammatory drugs) and medications for acid reflux such as cimetidine (Tagamet). If you're taking warfarin and start a new prescription or over-the-counter medication, check with ...

  20. Aneurysmal subarachnoid hemorrhage in patients taking direct oral anticoagulants: A case series and discussion of management

    Directory of Open Access Journals (Sweden)

    Joseph H. McMordie, MD

    2018-03-01

    Full Text Available Direct oral anticoagulants are becoming more commonplace for the treatment of nonvalvular atrial fibrillation and deep vein thrombosis. Unfortunately, effective reversal agents are not widely available limiting options for neurosurgical intervention during active anticoagulation. We report a case series of 3 patients treated for aneurysmal subarachnoid hemorrhage while taking direct oral anticoagulants. All three underwent open surgical clipping after adequate time was allowed for drug metabolism. Decision-making must take into account timing of intervention, drug half-life, and currently available reversal agents.

  1. Tailoring the surface properties of polypropylene films through cold atmospheric pressure plasma (CAPP) assisted polymerization and immobilization of biomolecules for enhancement of anti-coagulation activity

    Science.gov (United States)

    Navaneetha Pandiyaraj, K.; Ram Kumar, M. C.; Arun Kumar, A.; Padmanabhan, P. V. A.; Deshmukh, R. R.; Bah, M.; Ismat Shah, S.; Su, Pi-Guey; Halleluyah, M.; Halim, A. S.

    2016-05-01

    Enhancement of anti-thrombogenic properties of polypropylene (PP) to avert the adsorption of plasma proteins (fibrinogen and albumin), adhesion and activation of the platelets are very important for vast biomedical applications. The cold atmospheric pressure plasma (CAPP) assisted polymerization has potential to create the specific functional groups such as Osbnd Cdbnd O, Cdbnd O, Csbnd N and Ssbnd S. on the surface of polymeric films using selective precursor in vapour phase to enhance anti-thrombogenic properties. Such functionalized polymeric surfaces would be suitable for various biomedical applications especially to improve the blood compatibility. The eventual aspiration of the present investigation is to develop the biofunctional coating onto the surface of PP films using acrylic acid (AAc) and polyethylene glycol (PEG) as a precursor in a vapour phase by incorporating specific functional groups for immobilization of biomolecules such as heparin (HEP), chitosan (CHI) and insulin (INS) on the surface of plasma modified PP films. The surface properties such as hydrophilicity, chemical composition, surface topography of the surface modified PP films were analyzed by contact angle (CA), Fourier transform infrared spectroscopy (FTIR), X-ray photo electron spectroscopy (XPS) and atomic force microscopy (AFM). Furthermore the anti-thrombogenic properties of the surface modified PP films were studied by in vitro tests which include platelet adhesion and protein adsorption analysis. It was found that the anti-thrombogenic properties of the PP films are effectively controlled by the CAPP grafting of AAc and PEG followed by immobilization of biomolecules of heparin, chitosan and insulin. The grafting and immobilization was confirmed by FTIR and XPS through the recognition of specific functional groups such as COOH, Csbnd O, Ssbnd S and Csbnd N. on the surface of PP film. Furthermore, the surface morphology and hydrophilic nature of the PP films also tailored

  2. Tailoring the surface properties of polypropylene films through cold atmospheric pressure plasma (CAPP) assisted polymerization and immobilization of biomolecules for enhancement of anti-coagulation activity

    Energy Technology Data Exchange (ETDEWEB)

    Navaneetha Pandiyaraj, K., E-mail: dr.knpr@gmail.com [Surface Engineering Laboratory, Department of Physics, Sri Shakthi Institute of Engineering and Technology, L& T By Pass, Chinniyam Palayam (Post), Coimbatore 641062 (India); Ram Kumar, M.C.; Arun Kumar, A. [Surface Engineering Laboratory, Department of Physics, Sri Shakthi Institute of Engineering and Technology, L& T By Pass, Chinniyam Palayam (Post), Coimbatore 641062 (India); Padmanabhan, P.V.A. [PSN College of Engineering and Technology, Tirunelveli 627 152 (India); Deshmukh, R.R. [Department of Physics, Institute of Chemical Technology, Matunga, Mumbai 400 019 (India); Bah, M.; Ismat Shah, S. [Department of Physics and Astronomy, Department of Materials Science and Engineering, University of Delaware, 208 Dupont Hall, Newark (United States); Su, Pi-Guey [Department of Chemistry, Chinese Culture University, Taipei 111, Taiwan (China); Halleluyah, M.; Halim, A.S. [School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2016-05-01

    Graphical abstract: - Highlights: • Developed low cost cold atmospheric plasma reactor for plasma polymerization technique. • Surface of the PP film was modified by grafting of AAc and PEG by CAPP polymerization. • Biomolecules of chitosan, insulin and heparin were immobilized on surface of PEG-AAc grafted PP films. • The surface modified PP films were characterized by various techniques. • The plasma polymerized and immobilized film reveals substantial blood compatibility. - Abstract: Enhancement of anti-thrombogenic properties of polypropylene (PP) to avert the adsorption of plasma proteins (fibrinogen and albumin), adhesion and activation of the platelets are very important for vast biomedical applications. The cold atmospheric pressure plasma (CAPP) assisted polymerization has potential to create the specific functional groups such as O−C=O, C=O, C−N and S−S. on the surface of polymeric films using selective precursor in vapour phase to enhance anti-thrombogenic properties. Such functionalized polymeric surfaces would be suitable for various biomedical applications especially to improve the blood compatibility. The eventual aspiration of the present investigation is to develop the biofunctional coating onto the surface of PP films using acrylic acid (AAc) and polyethylene glycol (PEG) as a precursor in a vapour phase by incorporating specific functional groups for immobilization of biomolecules such as heparin (HEP), chitosan (CHI) and insulin (INS) on the surface of plasma modified PP films. The surface properties such as hydrophilicity, chemical composition, surface topography of the surface modified PP films were analyzed by contact angle (CA), Fourier transform infrared spectroscopy (FTIR), X-ray photo electron spectroscopy (XPS) and atomic force microscopy (AFM). Furthermore the anti-thrombogenic properties of the surface modified PP films were studied by in vitro tests which include platelet adhesion and protein adsorption analysis. It was

  3. Tailoring the surface properties of polypropylene films through cold atmospheric pressure plasma (CAPP) assisted polymerization and immobilization of biomolecules for enhancement of anti-coagulation activity

    International Nuclear Information System (INIS)

    Navaneetha Pandiyaraj, K.; Ram Kumar, M.C.; Arun Kumar, A.; Padmanabhan, P.V.A.; Deshmukh, R.R.; Bah, M.; Ismat Shah, S.; Su, Pi-Guey; Halleluyah, M.; Halim, A.S.

    2016-01-01

    Graphical abstract: - Highlights: • Developed low cost cold atmospheric plasma reactor for plasma polymerization technique. • Surface of the PP film was modified by grafting of AAc and PEG by CAPP polymerization. • Biomolecules of chitosan, insulin and heparin were immobilized on surface of PEG-AAc grafted PP films. • The surface modified PP films were characterized by various techniques. • The plasma polymerized and immobilized film reveals substantial blood compatibility. - Abstract: Enhancement of anti-thrombogenic properties of polypropylene (PP) to avert the adsorption of plasma proteins (fibrinogen and albumin), adhesion and activation of the platelets are very important for vast biomedical applications. The cold atmospheric pressure plasma (CAPP) assisted polymerization has potential to create the specific functional groups such as O−C=O, C=O, C−N and S−S. on the surface of polymeric films using selective precursor in vapour phase to enhance anti-thrombogenic properties. Such functionalized polymeric surfaces would be suitable for various biomedical applications especially to improve the blood compatibility. The eventual aspiration of the present investigation is to develop the biofunctional coating onto the surface of PP films using acrylic acid (AAc) and polyethylene glycol (PEG) as a precursor in a vapour phase by incorporating specific functional groups for immobilization of biomolecules such as heparin (HEP), chitosan (CHI) and insulin (INS) on the surface of plasma modified PP films. The surface properties such as hydrophilicity, chemical composition, surface topography of the surface modified PP films were analyzed by contact angle (CA), Fourier transform infrared spectroscopy (FTIR), X-ray photo electron spectroscopy (XPS) and atomic force microscopy (AFM). Furthermore the anti-thrombogenic properties of the surface modified PP films were studied by in vitro tests which include platelet adhesion and protein adsorption analysis. It was

  4. Compatibility of Injectable Anticoagulant Agents in Ethanol; In Vitro Antibiofilm Activity and Impact on Polyurethane Catheters of Enoxaparin 400 U/mL in 40% v/v Ethanol.

    Directory of Open Access Journals (Sweden)

    Damien Balestrino

    Full Text Available Interdialytic lock solutions should maintain catheter patency and prevent catheter infections. We aimed to determine in which conditions injectable anticoagulant agents (IAAs combined with ethanol are compatible and to assess the antibiofilm activity of the selected combination and its effects on dialysis catheters (DC.The solubility and compatibility of unfractionated heparin (UFH, low molecular weight heparins (LMWHs, heparinoids and fondaparinux (50 to 2,500 U/mL in 30 to 70% ethanol were determined by visual observation. The stability of enoxaparin in ethanol and the ethanol content were assessed by high performance liquid chromatography (HPLC and titrimetric control, respectively. The bactericidal effect was determined on 24h-old biofilms embedded in silicone-DC. The integrity of polyurethane-DC immersed in anticoagulant-ethanol was assessed by gas chromatography-mass spectrometry (GC-MS and compared with previously published results.The compatibility of IAAs and ethanol varied according to IAA type and concentration, and ethanol content. UFH in 40% ethanol was not compatible, whatever the UFH concentration used. Established limits of compatibility of enoxaparin, nadroparin, dalteparin and tinzaparin in 40% ethanol were 1350, 575, 307 and 207 U/ml, respectively, and up to 300 U/ml for danaparoid and 1 mg/mL for fondaparinux. Enoxaparin 400 U/mL in 40% ethanol (Enox/Eth eradicated biofilm after 4 hours of exposure for Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans and after 24 hours for Klebsiella pneumoniae and S. aureus. Aliphatic carbonate and alcohol compounds were released by polyurethane-DC after Enox/Eth exposure, as after 40% ethanol or saline exposure. There was no significant difference between the amounts released after 30 minutes of exposure to Enox/Eth and 15 days to saline.A 40% ethanol solution can be combined with all IAAs but UFH. Enox/Eth was effective as an anti-biofilm agent with minor impacts on

  5. Methylphenidate Actively Induces Emergence from General Anesthesia

    Science.gov (United States)

    Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F.K.; Chemali, Jessica J.; Brown, Emery N.

    2011-01-01

    Background Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study we tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane anesthesia. Methods Using adult rats we tested the effect of methylphenidate IV on time to emergence from isoflurane anesthesia. We then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate–induced restoration of righting during continuous isoflurane anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Droperidol IV was administered to test for inhibition of methylphenidate's actions. Results Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without compared to with methylphenidate was 200 [155, 331] s (median, [95% confidence interval]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta to theta, and induced an increase in minute ventilation. Administration of droperidol (0.5 mg/kg IV) prior to methylphenidate (5 mg/kg IV) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions Methylphenidate actively induces emergence from isoflurane anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. Our findings suggest that methylphenidate may be clinically

  6. Marine pharmacology in 2001--2002: marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action.

    Science.gov (United States)

    Mayer, Alejandro M S; Hamann, Mark T

    2005-01-01

    During 2001--2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors' 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001--2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories.

  7. Selection of an aptamer antidote to the anticoagulant drug bivalirudin.

    Directory of Open Access Journals (Sweden)

    Jennifer A Martin

    Full Text Available Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT. Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug, and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.

  8. Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Radiology Department (United Kingdom); Shiach, Caroline, E-mail: caroline.shiach@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)

    2017-03-15

    The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

  9. Overview of a pharmacist anticoagulation certificate program.

    Science.gov (United States)

    Kirk, Julienne K; Edwards, Rebecca; Brewer, Andrew; Miller, Cathey; Bray, Bryan; Groce, James B

    2017-07-01

    To describe the design of an ongoing anticoagulation certificate program and annual renewal update for pharmacists. Components of the anticoagulation certificate program include home study, pre- and posttest, live sessions, case discussions with evaluation and presentation, an implementation plan, and survey information (program evaluation and use in practice). Clinical reasoning skills were assessed through case work-up and evaluation prior to live presentation. An annual renewal program requires pharmacists to complete home study and case evaluations. A total of 361 pharmacists completed the anticoagulation certificate program between 2002 and 2015. Most (62%) practiced in ambulatory care and 38% in inpatient care settings (8% in both). In the past four years, 71% were working in or starting anticoagulation clinics in ambulatory and inpatient settings. In their evaluations of the program, an average of 90% of participants agreed or strongly agreed the lecture material was relevant and objectives were met. Pharmacists are able to apply knowledge and skills in management of anticoagulation. This structured practice-based continuing education program was intended to enhance pharmacy practice and has achieved that goal. The certificate program in anticoagulation was relevant to pharmacists who attended the program. Copyright © 2017. Published by Elsevier Inc.

  10. Reduction of circulating annexin A5 levels and resistance to annexin A5 anticoagulant activity in women with recurrent spontaneous pregnancy losses.

    NARCIS (Netherlands)

    Rand, J.H.; Arslan, A.A.; Wu, X.X.; Wein, R.; Mulholland, J.; Shah, M.; Heerde, W.L. van; Reutelingsperger, C.P.M.; Lockwood, C.J.; Kuczynski, E.

    2006-01-01

    OBJECTIVE: We investigated whether levels of annexin A5, evidence for resistance to annexin A5 activity, and levels anti-annexin A5 antibodies might be altered in women with a history of recurrent spontaneous pregnancy losses. STUDY DESIGN: These annexin A5 parameters were assayed in 70 nonpregnant

  11. Management of anticoagulation in hip fractures: A pragmatic approach.

    Science.gov (United States)

    Yassa, Rafik; Khalfaoui, Mahdi Yacine; Hujazi, Ihab; Sevenoaks, Hannah; Dunkow, Paul

    2017-09-01

    Hip fractures are common and increasing with an ageing population. In the United Kingdom, the national guidelines recommend operative intervention within 36 hours of diagnosis. However, long-term anticoagulant treatment is frequently encountered in these patients which can delay surgical intervention. Despite this, there are no set national standards for management of drug-induced coagulopathy pre-operatively in the context of hip fractures.The aim of this study was to evaluate the management protocols available in the current literature for the commonly encountered coagulopathy-inducing agents.We reviewed the current literature, identified the reversal agents used in coagulopathy management and assessed the evidence to determine the optimal timing, doses and routes of administration.Warfarin and other vitamin K antagonists (VKA) can be reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg intravenously to correct coagulopathy.The role of fresh frozen plasma is not clear from the current evidence while prothrombin complex remains a reliable and safe method for immediate reversal of VKA-induced coagulopathy in hip fracture surgery or failed vitamin K treatment reversal.The literature suggests that surgery should not be delayed in patients on classical antiplatelet medications (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be avoided for the latter. However, evidence regarding the use of more novel antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains a largely unexplored area in the context of hip fracture surgery. We suggest treatment protocols based on best available evidence and guidance from allied specialties.Hip fracture surgery presents a common management dilemma where semi-urgent surgery is required. In this article, we advocate an evidence-based algorithm as a guide for managing these anticoagulated patients. Cite this article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

  12. Thromboembolic and bleeding risks in patients undergoing atrial fibrillation ablation: oral anticoagulation perspectives.

    Science.gov (United States)

    Briceño, David F; Madan, Nidhi; Romero, Jorge; Londoño, Alejandra; Villablanca, Pedro A; Natale, Andrea; Di Biase, Luigi

    2017-07-01

    Atrial fibrillation (AF) is a cause of significant morbidity and mortality. Catheter ablation for AF (CAAF) has emerged as an effective treatment option of rhythm control for patients with symptomatic AF. However, the risk of thromboembolism and bleeding in the periprocedural period represent a worrisome complication of this therapy. The reported incidence of thromboembolic and bleeding events associated with CAAF varies from 0.9% to 5% depending on the CAAF strategy and the anticoagulation regimen used in the periprocedural period. Areas covered: The different anticoagulation regimens used prior to, during, and after CAAF to minimize the risk of thromboembolic and bleeding events are reviewed. The use of uninterrupted oral anticoagulation and appropriate heparin dosing to achieve safe activated clotting time levels are also detailed. A comprehensive approach with assessment of individual risk for thromboembolic and bleeding complications, and understanding the pharmacokinetics of the anticoagulant agents available is also reviewed. Expert opinion: The key advances done in the periprocedural anticoagulation field include the use of uninterrupted anticoagulation strategies in patients undergoing AF ablation and efforts to simplify the selection of patients who need LAA thrombus screening prior to ablation.

  13. Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles.

    Science.gov (United States)

    Degoutin, S; Jimenez, M; Casetta, M; Bellayer, S; Chai, F; Blanchemain, N; Neut, C; Kacem, I; Traisnel, M; Martel, B

    2012-06-01

    The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop.

  14. Exploring potential anticoagulant drug formulations using thrombin generation test

    Directory of Open Access Journals (Sweden)

    Elena Zavyalova

    2016-03-01

    The thrombin generation test was used to assess the whole coagulation cascade in normal and factor-deficient human blood plasma. Potential therapeutic windows were estimated for coagulation factors, ranking them as targets for anticoagulant drugs. Thrombin and factor Xa have been revealed as the most promising targets, which fully agrees with the current drug development strategy. Inhibitors of factors Va and VIIa are expected to have narrow therapeutic windows. Inhibitors of factors VIIIa and IXa are expected to have a moderate anticoagulant effect. Factors XI and XII are poor targets for anticoagulant drugs. Compared with plasma that is deficient in factor II, the thrombin inhibitors bivalirudin and aptamer HD1 had increased activity. Both inhibitors were tested in deficient plasma providing a model of potential drug combination. The most promising combinations were anti-thrombin with anti-V/Va and also anti-thrombin with anti-IX/IXa. Each combination had an incremental dose-effect dependence that is promising from the standpoint of the therapeutic window.

  15. Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles

    International Nuclear Information System (INIS)

    Degoutin, S; Jimenez, M; Casetta, M; Bellayer, S; Chai, F; Blanchemain, N; Neut, C; Kacem, I; Traisnel, M; Martel, B

    2012-01-01

    The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop. (paper)

  16. Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis.

    Science.gov (United States)

    Kitazawa, Fumiaki; Fuchida, Shin-Ichi; Ise, Fumitaka; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2017-07-01

    The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light-chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low-dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7-fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy-induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin-6. In conclusion, clinically important interactions between warfarin and lenalidomide and low-dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values signi ficantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.

  17. APOLLO I: Anticoagulation control in atrial fibrillation.

    Science.gov (United States)

    Pinho-Costa, Luís; Moreira, Sónia; Azevedo, Cristiana; Azevedo, Pedro; Castro, Elisabete; Sousa, Hélder; Melo, Miguel

    2015-05-01

    Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p0.05). Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  18. Does current oral antiplatelet agent or subtherapeutic anticoagulation use have an effect on tissue-plasminogen-activator-mediated recanalization rate in patients with acute ischemic stroke?

    Science.gov (United States)

    Ibrahim, Mohamed M; Sebastian, Joseph; Hussain, Muhammad; Al-Hussain, Fawaz; Uchino, Ken; Molina, Carlos; Khan, Khurshid; Demchuk, Andrew M; Alexandrov, Andrei V; Saqqur, Maher

    2010-01-01

    Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤ 2) using χ(2) test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60

  19. Improvement in long-term ECMO by detailed monitoring of anticoagulation: a case report.

    Science.gov (United States)

    Sievert, Alicia; Uber, Walter; Laws, Stacey; Cochran, Joel

    2011-01-01

    The use of unfractionated heparin (UFH) as an anticoagulant during long-term extracorporeal support presents a unique challenge for the clinician in balancing the amount of anticoagulant to maintain adequate anticoagulation without causing excessive bleeding. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) are the most common modality to monitor UFH on extracorporeal membrane oxygenation (ECMO). Limitations to these tests include consumptive coagulopathies, clotting factor deficiencies, platelet dysfunction, and fibrinolysis. The following case report describes the use of alternative monitoring strategies to assess more accurately anticoagulation during ECMO. A 20-month-old female presented to the emergency department with a 5-6 day history of cough, fever, tachypnea, and respiratory distress. She was diagnosed with influenza A and B with pneumonia. The patient was placed on veno-venous ECMO (V-V ECMO) after mechanical ventilation failed. On ECMO day eight, the patient developed a thrombus in her inferior vena cava and pleural effusions, obstructing cannula flow. Laboratory tests revealed the ACT was within range, yet the aPTT was dropping, despite increased heparin. Heparin levels were low and antithrombin-III (AT) concentrations were 40%. Recombinant AT was given and subsequent aPTTs were within the therapeutic range. Later, the aPTT decreased to 475 mg/ dL, and Factor VIII >150 IU/dL, suggesting an acute phase reaction or ongoing systemic inflammation, increasing the risk for thrombosis. We maintained heparin assays between 0.5-0.7 IU/mL and AT >60% to assure heparin's effect. The patient showed no signs of excess bleeding, blood product administration, or clots in the circuit, suggesting proper anticoagulation. The patient was successfully weaned on day 33 and is currently alive and at home. Monitoring of anti-Xa UFH and AT proved effective for measuring anticoagulation and detecting inconsistencies in other anticoagulation

  20. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury

    NARCIS (Netherlands)

    Hofstra, Jorrit J; Vlaar, Alexander P; Cornet, Alexander D; Dixon, Barry; Roelofs, Joris J; Choi, Goda; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

    BACKGROUND: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury. METHODS: Male Sprague-Dawley rats were intravenously

  1. Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation.

    Science.gov (United States)

    Couch, Yvonne; Akbar, Naveed; Davis, Simon; Fischer, Roman; Dickens, Alex M; Neuhaus, Ain A; Burgess, Annette I; Rothwell, Peter M; Buchan, Alastair M

    2017-08-01

    Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. EVs were quantified and analyzed in the sera of patients after an acute stroke (size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression. Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells. © 2017 American Heart Association, Inc.

  2. [The study of anticoagulants selection in platelet-rich plasma preparation].

    Science.gov (United States)

    Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

    2015-07-01

    To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

  3. Citrate Anticoagulation during Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Ricci, Davide; Panicali, Laura; Facchini, Maria Grazia; Mancini, Elena

    2017-01-01

    During extracorporeal dialysis, some anticoagulation strategy is necessary to prevent the coagulation of blood. Heparin has historically been used as an anticoagulant because of its efficacy combined with low cost. However, a variable incidence of hemorrhagic complications (5-30%) has been documented in patients undergoing continuous renal replacement therapy (CRRT) with heparin as an anticoagulant. Citrate has anticoagulation properties secondary to its ability to chelate calcium, which is necessary for the coagulation cascade. Citrate may thus be used in a regional anticoagulation (RCA), limited to the extracorporeal circuit of CRRT, to avoid systemic anticoagulation. Recent meta-analysis confirmed the advantage of RCA over heparin in terms of incidence of bleeding during CRRT. Moreover, an increase in filter lifespan is documented, with a secondary advantage in reaching the prescribed dialysis dose. In our experience, we could confirm this positive effect. In fact, with a progressive increase in the proportion of CRRT with citrate as RCA, we obtained a reduction in the number of filters used for every 72 h of treatment (from 2.4 in 2011 to 1.3 in 2015), and most importantly, a reduction in the difference between the prescribed and delivered dialysis doses (from 22 to 7%). Citrate has an intense effect on the acid-base balance as well, if fully metabolized through the Krebs cycle, due to the production of bicarbonate. Even more severely ill patients, such as those with liver dysfunction, may be treated with RCA without severe complications, because modern machines for CRRT are equipped with simple systems that are able to manage the citrate infusion and control the calcium levels, with minimal risks of metabolic derangements. © 2017 S. Karger AG, Basel.

  4. Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

    Science.gov (United States)

    Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

    2016-06-01

    Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

  5. Fatal pulmonary hemorrhage after taking anticoagulation medication

    Directory of Open Access Journals (Sweden)

    Samuel P. Hammar

    2015-01-01

    Full Text Available We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban.

  6. Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

    Science.gov (United States)

    Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

    2015-12-01

    A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Current State of Anticoagulants to Treat Deep Venous Thrombosis

    OpenAIRE

    Vo, Timothy; Vazquez, Sara; Rondina, Matthew T.

    2014-01-01

    Anticoagulation remains the cornerstone of treatment in patients with deep vein thrombosis (DVT). While parenteral anticoagulants and oral vitamin K antagonists (e.g. warfarin) have been used for many decades, the recent development of novel oral anticoagulants have provided clinicians with an expanding set of therapeutic options for DVT. This review summarizes the pharmacology and clinical trial results of these new oral anticoagulants. Several practical considerations to the use of these or...

  8. Characterization and structural analysis of a potent anticoagulant phospholipase A2 from Pseudechis australis snake venom.

    Science.gov (United States)

    Du, Qianyun Sharon; Trabi, Manuela; Richards, Renée Stirling; Mirtschin, Peter; Madaras, Frank; Nouwens, Amanda; Zhao, Kong-Nan; de Jersey, John; Lavin, Martin F; Guddat, Luke W; Masci, Paul P

    2016-03-01

    Pseudechis australis is one of the most venomous and lethal snakes in Australia. Numerous phospholipase A2 (PLA2) isoforms constitute a major portion of its venom, some of which have previously been shown to exhibit not only enzymatic, but also haemolytic, neurotoxic and anticoagulant activities. Here, we have purified a potent anticoagulant PLA2 (identified as PA11) from P. australis venom to investigate its phospholipase, anticoagulant, haemolytic and cytotoxic activities and shown that addition of 11 nM PA11 resulted in a doubling of the clotting time of recalcified whole blood. We have also demonstrated that PA11 has high PLA2 enzymatic activity (10.9 × 10(4) Units/mg), but low haemolytic activity (0.6% of red blood cells hydrolysed in the presence of 1 nM PA11). PA11 at a concentration lower than 600 nM is not cytotoxic towards human cultured cells. Chemical modification experiments using p-bromophenacyl bromide have provided evidence that the catalytic histidine of PA11 is critical for the anticoagulant activity of this PLA2. PA11 that was subjected to trypsin digestion without previous reduction and alkylation of the disulfide bonds maintained enzymatic and anticoagulant activity, suggesting that proteolysis alone cannot abolish these properties. Consistent with these results, administration of PA11 by gavage in a rabbit stasis thrombosis model increased the clotting time of recalcified citrated whole blood by a factor of four. These data suggest that PA11 has potential to be developed as an anticoagulant in a clinical setting. Copyright © 2015. Published by Elsevier Ltd.

  9. Coagulation, Fibrinolysis and Inhibitors in Failing Filters during Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: Effect of Anticoagulation Modalities.

    Science.gov (United States)

    Schilder, Louise; Nurmohamed, S Azam; ter Wee, Pieter M; Paauw, Nanne J; Girbes, Armand R J; Beishuizen, Albertus; Beelen, Robert H J; Groeneveld, A B Johan

    2015-01-01

    The mechanisms of early filter failure and clotting with different anticoagulation modalities during continuous venovenous hemofiltration (CVVH) are largely unknown. Citrate, heparin and no anticoagulation were compared. Blood was drawn pre- and post filter up to 720 min. Concentrations of the thrombin-antithrombin (TAT), activated protein C-protein C inhibitor (APC-PCI), and type I plasminogen activator inhibitor (PAI-1) were determined. In case of early filter failure (filter after 10 min in the heparin group than in other groups. In clotting filters, production of APC-PCI and PAI was also higher with heparin than citrate. Coagulation activation in plasma and inhibition of anticoagulation in plasma and filter may partly determine early CVVH filter failure due to clotting, particularly when heparin is used. Regional anticoagulation by citrate circumvents the inhibition of anticoagulation and fibrinolysis by platelet activation following heparin. © 2015 S. Karger AG, Basel.

  10. Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis.

    Science.gov (United States)

    Tufano, Antonella; Ageno, Walter; Di Micco, Pierpaolo; Niglio, Alferio; Rosa, Vladimir; Ballaz, Aitor; Braester, Andrei; Rubio, Carmen Mª; Isern, Virginia; Imbalzano, Egidio; Monreal, Manuel

    2018-02-27

    Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71-5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47-2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14-8.17) and anaemia (HR: 4.11; 95%CI: 1.45-11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68-10.1) were associated with at increased risk for major bleeding. The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. The pharmacology of recombinant hirudin, a new anticoagulant ...

    African Journals Online (AJOL)

    A new anticoagulant, recombinant hirudin, was given to healthy volunteers (5 per test dose) in single .intravenous doses of 0,01, 0,02, 0,04, 0,07 and 0,1 mg/kg to study its anticoagulant effects, how it was tolerated and its pharmacokinetics. Hirudin proved to be a potent anticoagulant with important effects on thrombin ...

  12. Anticoagulant Medicine: Potential for Drug-Food Interactions

    Science.gov (United States)

    ... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question Refer Patient ... Jewish Health wants you to be aware these drug-food interactions when taking anticoagulant medicine. Ask your health care ...

  13. Tamoxifen induces resistance to activated protein C.

    Science.gov (United States)

    Rühl, Heiko; Schröder, Lars; Müller, Jens; Fimmers, Rolf; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

    2014-05-01

    The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Blood samples were collected prospectively from women with breast cancer before (n=25) and monthly after start of adjuvant TAM treatment (n=75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. APC sensitivity decreased by 41% (p=0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p=0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Improving the quality of oral anticoagulant therapy

    NARCIS (Netherlands)

    Gadisseur, Alain Peter Anton

    2006-01-01

    Oral anticoagulant therapy has changed little since the development of the coumarin drugs after the Second World War. The basic nature of the therapy, i.e. the balancing between thrombosis and haemorrhage, makes it a therapy difficult to manage. Add to this the many influences from co-morbidity,

  15. ORIGINAL ARTICLES Guideline for Prophylactic Anticoagulation

    African Journals Online (AJOL)

    situation. It is hoped that this will lead to improved anticoagulation practice in this country, which we believe will directly benefit patient outcome. S Afr Med J 2004; 94: 691-695. • Certain thrombophilic states (antithrombin/protein C/ protein S deficiency, antiphospholipid syndrome). • Inflammatory bowel disease. • Pregnancy.

  16. Periprocedural reversal and bridging of anticoagulant treatment

    NARCIS (Netherlands)

    Levi, M.; Eerenberg, E.; Kamphuisen, P.W.

    2011-01-01

    Anticoagulants are effective agents in reducing the risk of thromboembolism but the most important adverse effect of these agents is the occurrence of bleeding. Bleeding complications may occur spontaneously but the risk of bleeding is particularly increased in case of trauma or around invasive

  17. Anticoagulation duration in heterozygous factor V Leiden: a decision analysis.

    Science.gov (United States)

    Donovan, Anna K; Smith, Kenneth J; Ragni, Margaret V

    2013-01-01

    Current anticoagulation guidelines suggest that optimal anticoagulation duration for unprovoked venous thromboembolism is determined by an individual risk assessment, balancing risks of anticoagulation bleeding with venous thromboembolism recurrence. Among individuals heterozygous for the factor V Leiden mutation, while venous thromboembolism recurrence risk is greater, the risk for bleeding is recognized to be lower, suggesting longer duration anticoagulation could be considered. The objective of this study was to compare standard vs. lifelong anticoagulation in 20-year-old factor V Leiden heterozygotes with unprovoked venous thromboembolism. A Markov state-transition model was used, incorporating risks of major, minor, and fatal anticoagulation bleeding, bleeding and thromboembolism morbidity and mortality, and quality of life utilities. Model parameter values favoring lifelong anticoagulation in factor V Leiden heterozygotes were determined in sensitivity analyses. Outcomes were in quality-adjusted life years, discounted at 3% per year. In general population groups with odds ratios for venous thromboembolism recurrence and anticoagulation bleeding of 1.0, a short-term anticoagulation strategy gained 0.09 quality-adjusted life years more than a lifelong anticoagulation strategy. By contrast, in factor V Leiden heterozygotes, lifetime anticoagulation was favored if their relative risk of venous thromboembolism was greater than 1.07 or their relative risk for bleeding was less than 0.91. Results were relatively insensitive to individual variation in other parameter values. Lifelong anticoagulation may benefit individuals heterozygous for factor V Leiden and previous idiopathic venous thromboembolism. Studies assessing bleeding risk with anticoagulation in factor V Leiden heterozygotes and the costs of indefinite anticoagulation are needed to determine if lifelong anticoagulation is the optimal strategy. © 2013 Elsevier Ltd. All rights reserved.

  18. Anticoagulant rodenticides and wildlife: Concluding remarks

    Science.gov (United States)

    van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

    2018-01-01

    Rodents are known to affect human society globally in various adverse ways, resulting in a widespread demand for their continuous control. Anticoagulant rodenticides (ARs) have been, and currently remain, the cornerstone of rodent control throughout the world. Although alternative control methods exist, they are generally less effective. ARs work by affecting vitamin K metabolism, thereby preventing the activation of blood clotting factors and eventual coagulopathy. Since ARs are non-selective, their undoubted benefits for rodent control have to be balanced against the environmental risks that these compounds pose. Although they have been used for decades, pharmacokinetic and toxicokinetic data are mainly available for laboratory mammals and have concentrated on acute effects. Limited information is available on chronic exposure scenarios and for wildlife species. Important gaps exist in our understanding of the large inter- and intra-species differences in sensitivity to ARs, especially for non-target species, and in our knowledge about the occurrence and importance of sub-lethal effects in wildlife. It is clear that mere presence of AR residues in the body tissues may not indicate the occurrence of effects, although unequivocal assessment of effects under field conditions is difficult. Ante-mortem symptoms, like lethargy, subdued behaviour and unresponsiveness are generally not very specific as is true for more generic post-mortem observations (e.g. pallor of the mucous membranes or occurrence of haemorrhages). It is only by combining ante or post-mortem data with information on exposure that effects in the field may be confirmed. We do know however that a wide variety of non-target species are directly exposed to ARs. Secondary exposure in predators is also widespread although there is limited information on whether this exposure causes actual effects. Exposure is driven by ecological factors and is context specific with respect to spatial habitat configuration

  19. Factors associated with availability of anticoagulation reversal agents in rural and community emergency departments.

    Science.gov (United States)

    Faine, Brett A; Amendola, Julie; Homan, Jordan; Ahmed, Azeemuddin; Mohr, Nicholas

    2018-01-15

    Results of a study of anticoagulation reversal agent availability in rural and community hospital emergency departments (EDs) are reported. A cross-sectional telephone survey was conducted to test the hypothesis that anticoagulation reversal agents are not commonly stocked in low-volume EDs. In phase 1 of the study, a physician, pharmacist, or nurse manager at a sample of EDs in 1 state was surveyed to characterize anticoagulation reversal agent availability and the presence or absence of reversal protocols; in phase 2, follow-up qualitative interviews were conducted with hospital pharmacists selected by purposive sampling to identify barriers to availability. Among the 103 EDs represented in the survey, 87 (84%) stocked fresh frozen plasma, 14 (14%) stocked 4-factor prothrombin complex concentrate (4F-PCC), and 2 (2%) stocked activated 4F-PCC. Forty-one EDs (40%) had a warfarin reversal protocol, but only 2 (2%) EDs had a protocol for direct oral anticoagulant reversal. ED volume and neurology coverage were significantly associated with reversal agent availability ( p = 0.014) and warfarin protocol availability ( p availability, and concerns about shelf life. An investigation of rural and community hospitals in 1 state revealed that the institutions rarely have specialized anticoagulation reversal drugs available. Cost and infrequency of utilization were 2 commonly cited reasons for reversal agent nonavailability. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  20. Stabilization of the E* Form Turns Thrombin into an Anticoagulant

    Energy Technology Data Exchange (ETDEWEB)

    Bah, Alaji; Carrell, Christopher J.; Chen, Zhiwei; Gandhi, Prafull S.; Di Cera, Enrico; (WU-MED)

    2009-07-31

    Previous studies have shown that deletion of nine residues in the autolysis loop of thrombin produces a mutant with an anticoagulant propensity of potential clinical relevance, but the molecular origin of the effect has remained unresolved. The x-ray crystal structure of this mutant solved in the free form at 1.55 {angstrom} resolution reveals an inactive conformation that is practically identical (root mean square deviation of 0.154 {angstrom}) to the recently identified E* form. The side chain of Trp215 collapses into the active site by shifting >10 {angstrom} from its position in the active E form, and the oxyanion hole is disrupted by a flip of the Glu192-Gly193 peptide bond. This finding confirms the existence of the inactive form E* in essentially the same incarnation as first identified in the structure of the thrombin mutant D102N. In addition, it demonstrates that the anticoagulant profile often caused by a mutation of the thrombin scaffold finds its likely molecular origin in the stabilization of the inactive E* form that is selectively shifted to the active E form upon thrombomodulin and protein C binding.

  1. The place of new oral anticoagulants in travel medicine.

    Science.gov (United States)

    Ringwald, Juergen; Grauer, Martin; Eckstein, Reinhold; Jelinek, Tomas

    2014-01-01

    New oral anticoagulants are increasingly used instead of vitamin K antagonists or low molecular weight heparins. Hence, more individuals treated with new oral anticoagulants will seek travel medicine advice. Travel medicine experts should therefore become familiar with new oral anticoagulants and with their impact and role in travel medicine. This review summarizes pharmacological characteristics and approved indications of dabigatran, rivaroxaban and apixaban, and highlights their relevance for travellers on permanent oral anticoagulation and for the prophylaxis of travellers' thrombosis. Compared to vitamin K antagonists, the new oral anticoagulants have many advantages: they do not have interactions with food, they have lower potential for drug-drug interactions and do not require regularly performed laboratory tests. The oral administration, obviating the need to carry needles and syringes during travel may give the new oral anticoagulants a further advantage over low molecular weight heparins. Clinical experience with the new oral anticoagulants, however, is still rather limited and there is concern regarding the clinical management of patients treated with new oral anticoagulants who suffer from severe bleeding or who need urgent invasive procedures. Overall, it remains an individual decision based on a risk/benefit analysis as to whether or not patients on long-term treatment with vitamin K antagonists should be switched to new oral anticoagulants for intended travel. Further caution is also indicated so that the availability of orally administered new anticoagulants should not lead to undifferentiated and unjustified prescription of anticoagulants for the prophylaxis of traveller's thrombosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Hematology of Nile tilapia (Oreochromis niloticus subjected to anesthesia and anticoagulation protocols

    Directory of Open Access Journals (Sweden)

    Nadia Cristine Weinert

    2015-12-01

    Full Text Available Clinical hematology facilitates the diagnosis of disease and can act as a prognostic indicator of pathological conditions in fish. The aim of the present study was to evaluate hematological parameters of Nile tilapia (Oreochromis niloticus subjected to different anesthetics and anticoagulants. Thirty apparently healthy fishes (average weight of 473 ± 35. 50 g and mean total length of 29. 33 ± 0. 37 cm, were selected from the local commercial fish farm in the Lages municipality (Santa Catarina, Brazil. The animals were randomly divided into three groups of 10. In two groups, anesthesia was induced with eugenol (70 mg·L- 1 (EG and Benzocaine hydrochloride (100 mg·L-1 (BG, respectively. Anesthesia was not administered to fish of the third group (CG/control group. Blood samples were obtained by venipuncture of the caudal vessels and placed into microtubes containing sodium heparin or Na2EDTA for further analysis. The results were analyzed by Sigma Stat for Windows, the paired t-test for significant differences between anticoagulants of the same group, and analysis of variance followed by the Tukey test for comparison of means between groups (p ? 0. 05. Most of the observed changes in the erythrogram were significantly higher for the anticoagulant heparin and benzocaine group in comparison to the control group. However, the values obtained for the leukogram were significantly higher for all groups subjected to the Na2EDTA anticoagulant, suggesting that heparin may cause cell clumping. The results suggest that the anesthetics under investigation effectively minimizes the effects of stress caused by handling and invasive procedures, and that the anticoagulant heparin causes less hemolysis in comparison to Na2EDTA for Nile tilapia. Thus, the hematological variations attributed to different anesthetic protocols and/or different anticoagulants should be considered for the species Oreochromis niloticus.

  3. Direct oral anticoagulants in the management of venous thromboembolism--evidence from major clinical trials.

    Science.gov (United States)

    Holy, Erik W; Beer, Jürg H

    2014-04-01

    For decades the antithrombotic management of venous thromboembolism (VTE) was limited to parenteral heparin formulations and oral vitamin K antagonists. Even though both classes of anticoagulants are effective, they have several limitations, including a narrow therapeutic window and the need to monitor anticoagulant activity. Direct oral anticoagulants (DOACs) that specifically target factor IIa or Xa have emerged. Recent data suggest that they are at least as effective and as safe as conventional therapy and have practical advantages, such as fixed dose regimen and no need for laboratory monitoring. Hence, they represent a major step forward in the acute treatment and long-term prevention of VTE. In this review, we outline the use of DOACs in the management of VTE and provide an overview of recently published major trials. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Anticoagulation in adults with congenital heart disease

    DEFF Research Database (Denmark)

    Jensen, A S; Idorn, L; Nørager, B

    2015-01-01

    Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events....... Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable....... It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts...

  5. Frontiers of anticoagulation therapy for atrial fibrillation.

    Science.gov (United States)

    Yamashita, Takeshi

    2011-07-01

    In the management of atrial fibrillation (AF), stroke prevention has been proved to play a pivotal role in addition to therapy for concomitant diseases. And, hitherto, anticoagulation by warfarin has been the only effective choice that is known to decrease the stroke rate with ∼70% risk reduction. Although the evidence has been rigid, there are many barriers not to make warfarin therapy pervasive. However, the principle of "KISS (keep it short and simple)" seems to alter our situations. Changing the complex pharmacology with warfarin into the simple pharmacology with new anticoagulants would lead us to a new paradigm, where the old book is now rewritten by a new language. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  6. Anticoagulation in acute ischemic stroke: A systematic search

    Directory of Open Access Journals (Sweden)

    Nayara L. Froio

    Full Text Available Summary Introduction: Stroke is one of the most important diseases worldwide. Several clinical scenarios demand full dose of anticoagulants primary to stroke etiology or to the treatment of comorbidity. However, controversy exists over many issues regarding anticoagulation treatment in stroke such as time for initiation, efficacy according to stroke etiology, the ideal dose of anticoagulants, and whether novel anticoagulants should be used. Method: Computerized search for clinical trials and randomized controlled clinical trials was done to the present date at Medline, Scielo, Embase, PsychInfo, and Cochrane Library using MeSH terms and the keywords stroke, ischemic stroke, anticoagulation, anticoagulants, heparin, low-molecular-weight heparin, warfarin, dabigatran, rivaroxaban, apixaban. The PRISMA statement was used to evaluate clinical trials. Results: Fourteen clinical trials were selected based on inclusion criteria. No evidence was found supporting the early use of heparin, heparinoids or low-molecular-weight heparin (LMWH early after stroke. No consistent evidence for the use of warfarin and the newer oral anticoagulants were found. Argatroban was the only anticoagulant with significant positive results early after large-artery ischemic stroke. Conclusion: The ideal time for initiating anticoagulation remains undefined, requiring further investigation. Early anticoagulation for ischemic stroke is not recommended, with few exceptions, such as that of argatroban.

  7. New oral anticoagulants--a review.

    Science.gov (United States)

    Ghanima, Waleed; Atar, Dan; Sandset, Per Morten

    2013-10-01

    Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

  8. Nanodiamonds activate blood platelets and induce thromboembolism.

    Science.gov (United States)

    Kumari, Sharda; Singh, Manoj K; Singh, Sunil K; Grácio, José J A; Dash, Debabrata

    2014-03-01

    Nanodiamonds (NDs) have been evaluated for a wide range of biomedical applications. Thus, thorough investigation of the biocompatibility of NDs has become a research priority. Platelets are highly sensitive and are one of the most abundant cell types found in blood. They have a central role in hemostasis and arterial thrombosis. In this study, we aim to investigate the direct and acute effects of carboxylated NDs on platelet function. In this study, pro-coagulant parameters such as platelet aggregability, intracellular Ca(2+) flux, mitochondrial transmembrane potential (ΔΨm), generation of reactive oxygen species, surface exposure of phosphatidylserine, electron microscopy, cell viability assay and in vivo thromboembolism were analyzed in great detail. Carboxylated NDs evoked significant activation of human platelets. When administered intravenously in mice, NDs were found to induce widespread pulmonary thromboembolism, indicating the remarkable thrombogenic potential of this nanomaterial. Our findings raise concerns regarding the putative biomedical applications of NDs pertaining to diagnostics and therapeutics, and their toxicity and prothrombotic properties should be critically evaluated.

  9. Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis Carinatus) Venom

    Science.gov (United States)

    Amrollahi Byoki, Elham; Zare Mirakabadi, Abbas

    2013-01-01

    Objective(s): Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus) was studied. Materials and Methods: Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT) and thrombin time (TT). Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC) with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results: Results of PT and TT tests for purified peptide (EC217) were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217) was about 30 KD. Conclusion: The present study showed that the venom of E. carinatus contains at least one anticoagulant factor. PMID:24494065

  10. Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis carinatus Venom

    Directory of Open Access Journals (Sweden)

    Elham Amrollahi Byoki

    2013-11-01

    Full Text Available   Objective(s: Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus was studied. Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT and thrombin time (TT. Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results of PT and TT tests for purified peptide (EC217 were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217 was about 30 KD. In conclusion, the present study showed that the venom of E. carinatus contains at least one anticoagulant factor.

  11. Evaluation of Marine Brown Algae and Sponges from Brazil as Anticoagulant and Antiplatelet Products

    Directory of Open Access Journals (Sweden)

    Suzi Meneses Ribeiro

    2011-08-01

    Full Text Available The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders.

  12. Gene activation by induced DNA rearrangements

    International Nuclear Information System (INIS)

    Schnipper, L.E.; Chan, V.; Sedivy, J.; Jat, P.; Sharp, P.A.

    1989-01-01

    A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

  13. [Retrospective analysis of correlative factors between digestive system injury and anticoagulant or antiplatelet-agents].

    Science.gov (United States)

    Cui, Ning; Luo, Hesheng

    2014-05-27

    To explore the correlative factors and clinical characteristics of digestive system injury during the treatment of anticoagulant and (or) antiplatelet-agents. A total of 1 443 hospitalized patients on anticoagulant and (or) antiplatelet-agents from January 2010 to December 2013 at Renmin Hospital of Wuhan University were analyzed retrospectively. Their length of hospital stay was from 5 to 27 days. Most of them were elderly males (n = 880, 61.0%) with an average age of (62 ± 6) years. 1 138 patients (78.9%) were farmers, workers or someone without a specific occupation. During the treatment of anticoagulant/antiplatelet-agents, statistical difference existed (P = 0.01) between positively and negatively previous digestive disease groups for actively newly occurring digestive system injury (16.0% (41/256) vs 15.9% (189/1 187)). After the dosing of anticoagulant and (or) antiplatelet-agents, 57 (66.3%, 57/86) patients were complicated by hemorrhage of digestive tract, taking 62.9% (61/97) of all positive result patients for Helicobacter pylori test. Comparing preventive PPI group with no PPI group, there was no marked statistical differences (P = 2.67) for digestive system complication (including hemorrhage of digestive tract) while receiving anticoagulant and (or) antiplatelet-agents (13.9% (74/533) vs 17.1% (156/910)). During anticoagulant and/or antiplatelet-agent therapy, 185 patients (12.8%) were complicated by peptic ulcer or peptic ulcer with bleeding, 40 patients (2.8%) had erosive gastritis and 5 (0.3%) developed acute gastric mucosal lesions. And 42 of 76 patients complicated by hemorrhage of digestive tract underwent endoscopic hemostasis while 2 patients were operated. Ninety-seven patients (6.7%) died, including 61 (62.9%, 61/97) from hemorrhage of digestive tract. The remainder became cured, improved and discharged. Moreover, no significant statistical differences existed (P = 2.29) among three combination group (aspirin, clopidogrel, warfarin), two

  14. Use of anticoagulants in elderly patients: practical recommendations

    Directory of Open Access Journals (Sweden)

    Helia Robert-Ebadi

    2009-04-01

    Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa

  15. Citrate anticoagulation in the ICU: the Leeds experience.

    Science.gov (United States)

    Trumper, Charlotte

    2016-09-08

    Continuous renal replacement therapy (CRRT) is widely used in the management of critically ill patients with acute kidney injury. It requires effective anticoagulation of the extracorporeal blood circuit. Although heparin is the most commonly prescribed anticoagulant, there are issues associated with heparin, and there has been increasing interest in regional citrate anticoagulation as an alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across the Trust. This article examines the reasons for the switch, the implementation of citrate and the impact of this quality-improvement project in terms of patient outcome data and feedback from the ICU nursing team.

  16. The mythology of anticoagulation therapy interruption for dental surgery.

    Science.gov (United States)

    Wahl, Michael J

    2018-01-01

    Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

  17. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

    NARCIS (Netherlands)

    Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

  18. Extraction of Anticoagulant Compound from Persian Gulf sea anemone Stichodactyla haddoni

    Directory of Open Access Journals (Sweden)

    Mahdeah Tahmasebi

    2015-07-01

    Full Text Available Background: The marine environment is anexceptional reservoir of bioactive natural products, many of them exhibit structural/chemical features that not found in terrestrial natural products.Glycosaminoglycans are one of this various bioactive compounds. Heparin, as a well known glycosaminoglycan, is a sulfated glycosaminoglycan that has natural anticoagulant properties. Heparin and heparin-like compounds are used as anticoagulants in many aspects of medicine. However, for two main reasons: 1. Contamination in heparin samples obtained from pig intestine or bovine lung pathogens and other pathogens, 2 .resource for use of heparin is limited and there are a lot of requirements for new compounds from natural resources. According to GAGs importance and widespread using of heparin in medicine, in the present study, GAGs compounds extracted from sea anemones and anticoagulant properties of the human blood is investigated. Materials and Methods: GAGs compound was extracted by using cetylpyridinium chloride. Anticoagulation activity of extracted GAGs (the extracted tentacle was tested in human blood plasma, using manual procedures, and assay system, prothrombin time (PT and activated partial thromboplastin time (APTT. Results: In this study the amount of the crude GAGs was 24 mg per gram of tentacle dry weight. The results ofanticoagulant activity extracted on human blood plasma showed that these compounds prolonged clotting time compared to the control. In APTT and PT assay of the extracted GAGs from the sea anemone also clotting time prolonged in compared to the control. Conclusion: The results demonstrated that anticoagulant compounds existed in the tentacle of the sea anemone, and although their effects is weaker than the heparin, but they can be substituted for heparin, at least in laboratory conditions.

  19. PHARMACOGENETIC ASPECTS OF NEW ORAL ANTICOAGULANTS APPLICATION

    Directory of Open Access Journals (Sweden)

    A. V. Kryukov

    2017-01-01

    Full Text Available The aim of this review is to assess the effect of genetic factors on the pharmacokinetic parameters of new oral anticoagulants. The review presents data from studies investigating the effect of gene polymorphisms that encode biotransformation enzymes and transporter proteins of new oral anticoagulants on the pharmacokinetics of these drugs. RE-LY study showed a 15% decrease in trough dabigatran concentration and 27% lower risk of bleeding in carriers of CES1 gene rs2244613 polymorphism, there was also a tendency to reduce the risk of major bleeding. Further study of CES1 gene rs8192935 polymorphism showed a 3% decrease in trough dabigatran concentration in heterozygotes and 11% in homozygotes. There was found a 2% and 3% decrease in trough concentrations in hetero- and homozygotes for the minor allele of CES1 gene rs2244613 polymorphism, respectively. There was no significant effect of ABCB1 gene rs2032582 and rs1045642 polymorphisms on dabigatran pharmacokinetics. It is known the case of gastrointestinal bleeding in the carrier of allelic variants of ABCB1 gene rs2032582 and rs1045642 polymorphisms. However, there was no significant effect of genotype on rivaroxaban pharmacokinetics in the study involving the carriers of ABCB1 gene rs2032582 and rs1045642 polymorphisms. ABCB1 gene rs4148738 polymorphism was associated with higher apixaban peak concentration. But groups of patients with acute cardioembolic stroke showed no statistically significant difference of apixaban peak concentration depending on ABCB1 gene rs1045642 polymorphism genotype. ABCB1 gene rs1045642 and SLCO1B1 gene rs4149056 polymorphisms have no effect on edoxaban pharmacokinetics. Elevation of edoxaban metabolite concentration in carriers of SLCO1B1 gene allelic variants was not clinically significant because the proportion of metabolite is about 10% of the concentration of the main substance. It is necessary to provide large population studies with control of treatment

  20. The Role of Anticoagulation Clinics in the Era of New Oral Anticoagulants

    Directory of Open Access Journals (Sweden)

    Sophie Testa

    2012-01-01

    Full Text Available Anticoagulation Clinics (ACs are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs, but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.

  1. Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression.

    Science.gov (United States)

    Snow, S J; Cheng, W; Wolberg, A S; Carraway, M S

    2014-07-01

    Air pollution exposure is associated with cardiovascular events triggered by clot formation. Endothelial activation and initiation of coagulation are pathophysiological mechanisms that could link inhaled air pollutants to vascular events. Here we investigated the underlying mechanisms of increased endothelial cell procoagulant activity following exposure to soluble components of ultrafine particles (soluble UF). Human coronary artery endothelial cells (HCAEC) were exposed to soluble UF and assessed for their ability to trigger procoagulant activity in platelet-free plasma. Exposed HCAEC triggered earlier thrombin generation and faster fibrin clot formation, which was abolished by an anti-tissue factor (TF) antibody, indicating TF-dependent effects. Soluble UF exposure increased TF mRNA expression without compensatory increases in key anticoagulant proteins. To identify early events that regulate TF expression, we measured endothelial H2O2 production following soluble UF exposure and identified the enzymatic source. Soluble UF exposure increased endothelial H2O2 production, and antioxidants attenuated UF-induced upregulation of TF, linking the procoagulant responses to reactive oxygen species (ROS) formation. Chemical inhibitors and RNA silencing showed that NOX-4, an important endothelial source of H2O2, was involved in UF-induced upregulation of TF mRNA. These data indicate that soluble UF exposure induces endothelial cell procoagulant activity, which involves de novo TF synthesis, ROS production, and the NOX-4 enzyme. These findings provide mechanistic insight into the adverse cardiovascular effects associated with air pollution exposure. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Evaluation of analgesic, anti-inflammatory, anti-depressant and anti-coagulant properties of Lactuca sativa (CV. Grand Rapids) plant tissues and cell suspension in rats.

    Science.gov (United States)

    Ismail, Hammad; Mirza, Bushra

    2015-06-27

    Lactuca sativa (lettuce) has been traditionally used for relieving pain, inflammation, stomach problems including indigestion and lack of appetite. Moreover, the therapeutic significance of L. sativa includes its anticonvulsant, sedative-hypnotic and antioxidant properties. In the present study, the MC (methanol and chloroform; 1:1) and aqueous extracts of seed and leaf along with cell suspension exudate were prepared. These extracts were explored for their analgesic, anti-inflammatory, antidepressant and anticoagulant effects by hot plate analgesic assay; carrageenan induced hind paw edema test, forced swimming test and capillary method for blood clotting respectively in a rat model. The results were analyzed using one-way Analysis of Variance (ANOVA) followed by Turkey multiple comparison test. Interestingly, the extracts and the cell suspension exudate showed dual inhibition by reducing pain and inflammation. The results indicated that the aqueous extracts of leaf exhibited highest analgesic and anti-inflammatory activities followed by leaf MC, cell suspension exudate, seed aqueous and seed MC extracts. The current findings show that aqueous and MC extracts of seed have the least immobility time in the forced swimming test, which could act as an anti-depressant on the central nervous system. The leaf extracts and cell suspension exudate also expressed moderate anti-depressant activities. In anticoagulant assay, the coagulation time of aspirin (positive control) and MC extract of leaf was comparable, suggesting strong anti-coagulant effect. Additionally, no abnormal behavior or lethality was observed in any animal tested. Taken together, L. sativa can potentially act as a strong herbal drug due to its multiple pharmaceutical effects and is therefore of interest in drug discovery and development of formulations.

  3. Heparin but not citrate anticoagulation of blood preserves platelet function for prolonged periods.

    Science.gov (United States)

    Truss, N J; Armstrong, P C J; Liverani, E; Vojnovic, I; Warner, T D

    2009-11-01

    Current guidelines state that platelet aggregation studies should be conducted within 4 h of venepuncture because of the decline in sensitivity to platelet agonists. This constrains studies of platelet activity in clinical situations where samples need to be transported or there are unavoidable delays prior to assessment. The aim of the present study was to compare systematically the responses of platelets stored in the presence of either citrate or heparin, the two most widely used anti-coagulants, using a range of standard techniques. Blood was taken from healthy volunteers and either assessed immediately or stored at ambient temperature (18-25 degrees C) for 24 h. Platelet reactivity to a range of agonists was determined by a combination of 96-well plate techniques; light transmission aggregometry, thrombi adhesion, ATP and ADP release, and TxA(2) release; by whole blood aggregometry; and by PFA-100. Testing using 96-well plate techniques allowed for the simultaneous measurement of responses to multiple concentrations of multiple agonists. The responses of platelets from blood anti-coagulated with heparin were predominantly preserved in all assays after 24 h storage, whereas, responses of platelets stored in blood anti-coagulated with citrate were greatly diminished. Consequently, anti-coagulation with heparin, but not citrate, preserves platelet responses for up to 24 h as determined by a range of techniques.

  4. Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

    Directory of Open Access Journals (Sweden)

    MAURO S. G. PAVÃO

    2002-03-01

    Full Text Available Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75% and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25% disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin.Dermatam sulfato e heparina semelhantes aos glicosaminoglicanos de mamíferos, mas apresentando diferenças no grau e posição de sulfatação foram previamente isolados do corpo das ascídias Styela plicata e Ascidia nigra. Estas diferenças produzem efeitos profundos nas suas propriedades anticoagulantes. O dermatam sulfato de S. plicata, composto por resíduos de ácido alfa-L-idurônico 2-O-sulfatados e N-acetilgalactosamina 4-O-sulfatados é um potente anticoagulante devido a sua alta atividade de cofator II da heparina. Surpreendentemente, este polímero possui uma

  5. Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus)

    DEFF Research Database (Denmark)

    Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert

    2003-01-01

    Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...

  6. The pharmacology of recombinant hirudin, a new anticoagulant

    African Journals Online (AJOL)

    1990-09-01

    Sep 1, 1990 ... The pharmacology of recombinant hirudin, a new anticoagulant. B. H. MEYER, H. G. LUUS, F. O. MULLER, P. N. BADENHORST, H.-J. ROTHIG. Summary. A new anticoagulant, recombinant hirudin, was given to hea"hy volunteers (5 per test dose) in single .intravenous doses of 0,01, 0,02, 0,04, 0,07 and 0 ...

  7. MRI screening for chronic anticoagulation in atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Mark eFisher

    2013-10-01

    Full Text Available Anticoagulation is highly effective in preventing stroke due to atrial fibrillation, but numerous studies have demonstrated low utilization of anticoagulation for these patients. Assessment of clinicians’ attitudes on this topic indicate that fear of intracerebral hemorrhage (ICH, rather than appreciation of anticoagulant benefits, largely drives clinical decision-making for treatment with anticoagulation in atrial fibrillation. Risk stratification strategies have been used for anticoagulation benefits and hemorrhage risk, but ICH is not specifically addressed in the commonly used hemorrhage risk stratification systems. Cerebral microbleeds are cerebral microscopic hemorrhages demonstrable by brain MRI, indicative of prior microhemorrhages, and predictive of future risk of ICH. Prevalence of cerebral microbleeds increases with age; and cross-sectional and limited prospective studies generally indicate that microbleeds confer substantial risk of ICH in patients treated with chronic anticoagulation. MRI thus is a readily available and appealing modality that can directly assess risk of future ICH in patients receiving anticoagulants for atrial fibrillation. Incorporation of MRI into routine practice is, however, fraught with difficulties, including the uncertain relationship between number and location of microbleeds and ICH risk, as well as cost-effectiveness of MRI. A proposed algorithm is provided, and relevant advantages and disadvantages are discussed. At present, MRI screening appears most appropriate for a subset of atrial fibrillation patients, such as those with intermediate stroke risk, and may provide reassurance for clinicians whose concerns for ICH tend to outweigh benefits of anticoagulation.

  8. Utilization of oral anticoagulation in a teaching hospital in Nigeria ...

    African Journals Online (AJOL)

    The mean age of the patients was 53.4 years and more females than males were on anticoagulation and monitoring (F14:M12). The most common indications for anticoagulation include deep venous thrombosis/pulmonary embolism, congestive heart failure with atrial fibrillation and mitral valve disease with atrial fibrillation.

  9. Atrial Fibrillation in Embolic Stroke: Anticoagulant Therapy at UNTH ...

    African Journals Online (AJOL)

    Objective: The decision to commence anticoagulation in a patient with embolic stroke and atrial fibrillation (AF) is often a difficult one for many clinicians. The result can have significant impact on the patient. This study was therefore undertaken to review the use of anticoagulation in embolic stroke in the setting of atrial ...

  10. [Therapeutic equivalence of the new oral anticoagulants].

    Science.gov (United States)

    Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L

    2015-10-01

    In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy.

    Science.gov (United States)

    Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele

    2016-06-30

    This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice.

  12. Effects of computer-assisted oral anticoagulant therapy

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul

    2012-01-01

    : Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured...... prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements......UNLABELLED: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within...

  13. Polissacarídeos sulfatados isolados das clorofíceas Caulerpa racemosa e Caulerpa cupressoides – extração, fracionamento e atividade anticoagulante =Sulfated polysaccharides isolated from Caulerpa racemosa and Caulerpa cupressoides (Chlorophyceaes – extraction, fractionation and anticoagulant activity

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2010-04-01

    in 0.1 M sodium acetate buffer (pH 5.0 containing 5 mM cysteine and 5 mM EDTA, followed by fractionation on ion exchange DEAE-cellulose column with NaCl gradient. The obtained fractions were analyzed by 0.5% agarose gel electrophoresis and the anticoagulant activity measured by the activated partial thromboplastin time (APTT using normal human plasma, and compared to a standard heparin curve (193 IU mg-1. Similar chromatographic profiles of SP were shown on both species, butwith distinct mobility patterns, when the SP fractions were compared by electrophoresis. SP eluted with 0.75 M of NaCl modified the APTT, whose anticoagulant activities were only 21.23 and 24.36 IU mg-1 for C. racemosa and C. cupressoides, respectively. Therefore, anticoagulant SP isolated from chlorophyceaes showed effects inferior to heparin, and comparative studies of these molecules are also suggested as auxiliary tools in the identification of algae of the same genus.

  14. Clinical impact of a pharmacist-led inpatient anticoagulation service: a review of the literature

    Directory of Open Access Journals (Sweden)

    Lee T

    2016-05-01

    Full Text Available Tiffany Lee, Erin Davis, Jason Kielly School of Pharmacy, Memorial University, St John's, NL, Canada Background: Anticoagulant therapies provide management options for potentially life-threatening thromboembolic conditions. They also carry significant safety risks, requiring careful consideration of medication dose, close monitoring, and follow-up. Inpatients are particularly at risk, considering the widespread use of anticoagulants in hospitals. This has prompted the introduction of safety goals for anticoagulants in Canada and the USA, which recommend increased pharmacist involvement to reduce patient harm. The goal of this review is to evaluate the efficacy and safety of pharmacist-led inpatient anticoagulation services compared to usual or physician-managed care. Methods: This narrative review includes articles identified through a literature search of PubMed, Embase, and International Pharmaceutical Abstracts databases, as well as hand searches of the references of relevant articles. Full publications of pharmacist-managed inpatient anticoagulation services were eligible if they were published in English and assessed clinical outcomes. Results: Twenty-six studies were included and further divided into two categories: 1 autonomous pharmacist-managed anticoagulation programs (PMAPs and 2 pharmacist recommendation. Pharmacist management of heparin and warfarin appears to result in improvements in some surrogate outcomes (international normalized ratio [INR] stability and time in INR goal range, while results for others are mixed (time to therapeutic INR, length of stay, and activated partial thromboplastin time [aPTT] measures. There is also some indication that PMAPs may be associated with reduced patient mortality. When direct thrombin inhibitors are managed by pharmacists, there seems to be a shorter time to therapeutic aPTT and a greater percentage of time in the therapeutic range, as well as a decrease in the frequency of medication

  15. Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

    Science.gov (United States)

    Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

    2018-01-01

    Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

  16. Acupuncture safety in patients receiving anticoagulants: a systematic review.

    Science.gov (United States)

    Mcculloch, Michael; Nachat, Arian; Schwartz, Jonathan; Casella-Gordon, Vicki; Cook, Joseph

    2015-01-01

    Theoretically, acupuncture in anticoagulated patients could increase bleeding risk. However, precise estimates of bleeding complication rates from acupuncture in anticoagulated patients have not been systematically examined. To critically evaluate evidence for safety of acupuncture in anticoagulated patients. We searched PubMed, EMBASE, the Physiotherapy Evidence Database, and Google Scholar. Of 39 potentially relevant citations, 11 met inclusion criteria: 2 randomized trials, 4 case series, and 5 case reports. Seven provided reporting quality sufficient to assess acupuncture safety in 384 anticoagulated patients (3974 treatments). Minor-moderate bleeding related to acupuncture in an anticoagulated patient occurred in one case: a large hip hematoma, managed with vitamin K reversal and warfarin discontinuation following reevaluation of its medical justification. Blood-spot bleeding, typical for any needling/injection and controlled with pressure/cotton, occurred in 51 (14.6%) of 350 treatments among a case series of 229 patients. Bleeding deemed unrelated to acupuncture during anticoagulation, and more likely resulting from inappropriately deep needling damaging tissue or from complex anticoagulation regimens, occurred in 5 patients. No bleeding was reported in 2 studies (74 anticoagulated patients): 1 case report and 1 randomized trial prospectively monitoring acupuncture-associated bleeding as an explicit end point. Altogether, 1 moderate bleeding event occurred in 3974 treatments (0.003%). Acupuncture appears to be safe in anticoagulated patients, assuming appropriate needling location and depth. The observed 0.003% complication rate is lower than the previously reported 12.3% following hip/knee replacement in a randomized trial of 27,360 anticoagulated patients, and 6% following acupuncture in a prospective study of 229,230 all-type patients. Prospective trials would help confirm our findings.

  17. Erythrocytes induce proinflammatory endothelial activation in hypoxia.

    Science.gov (United States)

    Huertas, Alice; Das, Shonit R; Emin, Memet; Sun, Li; Rifkind, Joseph M; Bhattacharya, Jahar; Bhattacharya, Sunita

    2013-01-01

    Although exposure to ambient hypoxia is known to cause proinflammatory vascular responses, the mechanisms initiating these responses are not understood. We tested the hypothesis that in systemic hypoxia, erythrocyte-derived H(2)O(2) induces proinflammatory gene transcription in vascular endothelium. We exposed mice or isolated, perfused murine lungs to 4 hours of hypoxia (8% O(2)). Leukocyte counts increased in the bronchoalveolar lavage. The expression of leukocyte adhesion receptors, reactive oxygen species, and protein tyrosine phosphorylation increased in freshly recovered lung endothelial cells (FLECs). These effects were inhibited by extracellular catalase and by the removal of erythrocytes, indicating that the responses were attributable to erythrocyte-derived H(2)O(2). Concomitant nuclear translocation of the p65 subunit of NF-κB and hypoxia-inducible factor-1α stabilization in FLECs occurred only in the presence of erythrocytes. Hemoglobin binding to the erythrocyte membrane protein, band 3, induced the release of H(2)O(2) from erythrocytes and the p65 translocation in FLECs. These data indicate for the first time, to our knowledge, that erythrocytes are responsible for endothelial transcriptional responses in hypoxia.

  18. Chitin and stress induced protein kinase activation

    DEFF Research Database (Denmark)

    Kenchappa, Chandra Shekar; Azevedo da Silva, Raquel; Bressendorff, Simon

    2017-01-01

    The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide...... substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts....

  19. Initiation of anticoagulation in atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, A.; Staerk, L.; Fosbøl, E. L.

    2017-01-01

    Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... identified AF patients initiating either a VKA or a NOAC from 22 August 2011 until 30 September 2016. We compared patient characteristics including age, gender, comorbidities, concomitant pharmacotherapy and CHA2DS2-VASc and HAS-BLED scores in patients initiated on a VKA, dabigatran, rivaroxaban or apixaban....... Differences were examined using multivariable logistic regression models. Results: The study population comprised 51 981 AF patients of whom 19 989 (38.5%) were initiated on a VKA, 13 242 (25.5%) on dabigatran, 8475 (16.3%) on rivaroxaban and 10 275 (19.8%) on apixaban. Those patients initiated on apixaban...

  20. Perioperative management of anticoagulant users scheduled for glaucoma surgery: a survey among the Brazilian Glaucoma Society members

    Directory of Open Access Journals (Sweden)

    Marcos Balbino

    2013-12-01

    Full Text Available PURPOSE: To investigate and describe, among the members of the Brazilian Glaucoma Society (BGS, the practices regarding the perioperative management of anticoagulants (warfarin and aspirin use in patients scheduled for glaucoma surgery. METHODS: The active members of the Brazilian Glaucoma Society answered a questionnaire evaluating different aspects of their current perioperative management of glaucomatous patients taking warfarin or aspirin. RESULTS: A total of 52 participants returned a complete questionnaire. Warfarin or aspirin was routinely interrupted prior to glaucoma surgery by 82.7% of the respondents. The majority of the surgeons who discontinued these medications reported doing so 7 days prior to surgery and resumed their use the day after the procedure. Almost half of our interviewees reported hemorrhagic complications that could be related to anticoagulant therapy. A large number of the surgeons (86.5% preferred a particular surgical technique for anticoagulated patients; however, most of them (88.5% do not change the anesthetic planning in such patients. Finally, the majority of the participants (90.4% refer their anticoagulated patients to a preoperative appointment with a cardiologist or a general practitioner before the surgery. CONCLUSIONS: The majority of Brazilian Glaucoma Society members participating in this study interrupt either warfarin or aspirin prior to glaucoma surgery. Although there is scant information available in the literature to offer definitive guidance, most participants from the Brazilian Glaucoma Society seem to share the same opinion when it comes to perioperative management of anticoagulant users.

  1. Enhancing anticoagulation and endothelial cell proliferation of titanium surface by sequential immobilization of poly(ethylene glycol) and collagen

    International Nuclear Information System (INIS)

    Pan, Chang-Jiang; Hou, Yan-Hua; Ding, Hong-Yan; Dong, Yun-Xiao

    2013-01-01

    In the present study, poly(ethylene glycol) (PEG) and collagen I were sequentially immobilized on the titanium surface to simultaneously improve the anticoagulation and endothelial cell proliferation. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy analysis confirmed that PEG and collagen I were successfully immobilized on the titanium surface. Water contact angle results suggested the excellent hydrophilic surface after the immobilization. The anticoagulation experiments demonstrated that the immobilized PEG and collagen I on the titanium surface could not only obviously prevent platelet adhesion and aggregation but also prolong activated partial thromboplastin time (APTT), leading to the improved blood compatibility. Furthermore, immobilization of collagen to the end of PEG chain did not abate the anticoagulation. As compared to those on the pristine and PEG-modified titanium surfaces, endothelial cells exhibited improved proliferative profiles on the surface modified by the sequential immobilization of PEG and collagen in terms of CCK-8 assay, implying that the modified titanium may promote endothelialization without abating the blood compatibility. Our method may be used to modify the surface of blood-contacting biomaterials such as titanium to promote endothelialization and improve the anticoagulation, it may be helpful for development of the biomedical devices such as coronary stents, where endothelializaton and excellent anticoagulation are required.

  2. Active Intracystic Negative Pressure Could Induce Osteogenesis.

    Science.gov (United States)

    Castro-Núñez, Jaime

    2018-02-23

    Based on previous findings, the author introduces the term "sugosteogenesis," a biological phenomenon that occurs by using the Evocyst, a device that exerts active intracystic negative pressure. The term "sugosteogenesis" comes from the Latin word "sugo-," meaning "suck," and Greek words "osteo-," meaning "bone," and genesis, "origin."

  3. Experimentally induced stress validated by EMG activity.

    Directory of Open Access Journals (Sweden)

    Rosan Luijcks

    Full Text Available Experience of stress may lead to increased electromyography (EMG activity in specific muscles compared to a non-stressful situation. The main aim of this study was to develop and validate a stress-EMG paradigm in which a single uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity of the trapezius muscles was the response of interest. In addition to linear time effects, non-linear EMG time courses were also examined. Taking into account the hierarchical structure of the dataset, a multilevel random regression model was applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3-minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. EMG activity during the entire experiment was conform a priori expectations: the pre-stimulus phase showed a significantly higher mean EMG activity level compared to the other two phases, and an immediate EMG response to the stimulus was demonstrated. In addition, the analyses revealed significant non-linear EMG time courses in all three phases. Linear and quadratic EMG time courses were significantly modified by subjective anticipatory stress level, measured just before the start of the stress task. Linking subjective anticipatory stress to EMG stress reactivity revealed that subjects with a high anticipatory stress level responded with more EMG activity during the pre-stimulus stress phase, whereas subjects with a low stress level showed an inverse effect. Results suggest that the stress paradigm presented here is a valid test to quantify individual differences in stress susceptibility. Further studies with this paradigm are required to demonstrate its potential use in mechanistic clinical studies.

  4. CD18 activation epitopes induced by leukocyte activation

    NARCIS (Netherlands)

    Beals, C. R.; Edwards, A. C.; Gottschalk, R. J.; Kuijpers, T. W.; Staunton, D. E.

    2001-01-01

    The cell surface adhesion molecule LFA-1 coordinates leukocyte trafficking and is a costimulatory molecule for T cell activation. We developed a panel of mAbs that recognize activation epitopes on the CD18 subunit, and show that stimulation of T lymphocytes appears to be accompanied by a

  5. Hemorrhagic stroke and oral anticoagulants: What is to be done?

    Directory of Open Access Journals (Sweden)

    M. A. Domashenko

    2016-01-01

    Full Text Available Hemorrhagic stroke (HS is associated with high mortality and disability rates. Due to the introduction of the current guidelines for the prevention of systemic thromboembolic events in patients with atrial fibrillations and to an increase in the number of older patients, there has been a rise in the incidence of intracranial hemorrhage (ICH associated with the use of oral anticoagulants. The paper discusses medical treatment in patients with HS during therapy with vitamin K antagonists (warfarin and novel oral anticoagulants (dabigatran. rivaroxaban, apixaban, as well as an anticoagulant resumption policy after prior ICH in patients at high risk for thromboembolic events.

  6. Social Bookmarking Induced Active Page Ranking

    Science.gov (United States)

    Takahashi, Tsubasa; Kitagawa, Hiroyuki; Watanabe, Keita

    Social bookmarking services have recently made it possible for us to register and share our own bookmarks on the web and are attracting attention. The services let us get structured data: (URL, Username, Timestamp, Tag Set). And these data represent user interest in web pages. The number of bookmarks is a barometer of web page value. Some web pages have many bookmarks, but most of those bookmarks may have been posted far in the past. Therefore, even if a web page has many bookmarks, their value is not guaranteed. If most of the bookmarks are very old, the page may be obsolete. In this paper, by focusing on the timestamp sequence of social bookmarkings on web pages, we model their activation levels representing current values. Further, we improve our previously proposed ranking method for web search by introducing the activation level concept. Finally, through experiments, we show effectiveness of the proposed ranking method.

  7. Ultraviolet induced lysosome activity in corneal epithelium

    International Nuclear Information System (INIS)

    Cullen, A.P.

    1980-01-01

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm -2 to 10.000 Jm -2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm -2 and lens threshold (Hsub(L)) was 7.500 Jm -2 . The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.) [de

  8. c-Myc-Induced Extrachromosomal Elements Carry Active Chromatin

    Directory of Open Access Journals (Sweden)

    Greg Smith

    2003-03-01

    Full Text Available Murine Pre-13 lymphocytes with experimentally activated MycER show both chromosomal and extrachromosomal gene amplification. In this report, we have elucidated the size, structure, functional components of c-Myc-induced extrachromosomal elements (EEs. Scanning electron microscopy revealed that EEs isolated from MycER-activated Pre-B+ cells are an average of 10 times larger than EEs isolated from non-MycER-activated control Pre-B- cells. We demonstrate that these large c-Myc-induced EEs are associated with histone proteins, whereas EEs of non-MycER-activated Pre B- cells are not. Immunohistochemistry and Western blot analyses using pan -histone-specific, histone H3 phosphorylation-specific, histone H4 acetylation-specific antibodies indicate that a significant proportion of EEs analyzed from MycER-activated cells harbors transcriptionally competent and/or active chromatin. Moreover, these large, c-Myc-induced EEs carry genes. Whereas the total genetic make-up of these c-Myc-induced EEs is unknown, we found that 30.2% of them contain the dihydrofolate reductase (DHFR gene, whereas cyclin C (CCNC was absent. In addition, 50% of these c-Myc-activated Pre-B+ EEs incorporated bromodeoxyuridine (BrdU, identifying them as genetic structures that self-propagate. In contrast, EEs isolated from non-Myc-activated cells neither carry the DHFR gene nor incorporate BrdU, suggesting that c-Myc deregulation generates a new class of EEs.

  9. Misconceptions about mirror-induced motor cortex activation.

    NARCIS (Netherlands)

    Praamstra, P.; Torney, L.; Rawle, C.J.; Miall, R.C.

    2011-01-01

    Observation of self-produced hand movements through a mirror, creating an illusion of the opposite hand moving, was recently reported to induce ipsilateral motor cortex activation, that is, motor cortex activation for the hand in rest. The reported work goes far beyond earlier work on motor cortex

  10. Transcatheter Arterial Embolization of Concurrent Spontaneous Hematomas of the Rectus Sheath and Psoas Muscle in Patients Undergoing Anticoagulation

    International Nuclear Information System (INIS)

    Basile, Antonio; Medina, Jose Garcia; Mundo, Elena; Medina, Vicente Garcia; Leal, Rafael

    2004-01-01

    We report a case of concurrent rectus sheath and psoas hematomas in a patient undergoing anticoagulant therapy, treated by transcatheter arterial embolization (TAE) of inferior epigastric and lumbar arteries. Computed tomography (CT) demonstrated signs of active bleeding in two hematomas of the anterior and posterior abdominal walls. Transfemoral arteriogram confirmed the extravasation of contrast from the right inferior epigastric artery (RIEA). Indirect signs of bleeding were also found in a right lumbar artery (RLA). We successfully performed TAE of the feeding arteries. There have been few reports in the literature of such spontaneous hemorrhages in patients undergoing anticoagulation, successfully treated by TAE

  11. [Pathogenesis and Laboratory Findings in Antiphospholipid Syndrome, Especially Associated with Lupus Anticoagulant].

    Science.gov (United States)

    Ieko, Masahiro; Naito, Sumiyoshi; Yoshida, Mika; Takahashi, Nobuhiko

    2015-10-01

    Antiphospholipid syndrome (APS), an acquired thrombotic condition, is a complex clinical state characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Revised APS classification criteria are used for diagnosis, which include at least one clinical criterion (thrombosis or pregnancy loss) and at least one of the laboratory criteria [anticardiolipin antibodies, anti-β2GPI antibodies, lupus anticoagulant (LA)]. LA is also an independent risk factor for developing thrombosis, though some LA-positive cases have been reported to have a bleeding symptom. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to low prothrombin activity in patients with LA, and has recently been reported not only in children but also in adults We have encountered LA cases with bleeding and low coagulation factor activities except for prothrombin. Based on our findings, we propose that LA-positive cases with a bleeding symptom and characterized by low coagulation factor activity including prothrombin be termed lupus anticoagulant-associated coagulopathy (LAAC). Furthermore, coagulation factor autoantibodies are often detected in LAAC patients; thus, correct measurement of LA is important to distinguish LAAC patients from those possessing an inhibitor to coagulation factors such as acquired hemophilia A as well as to select the optimal therapeutic strategy.

  12. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests.

    Science.gov (United States)

    Halbmayer, Walter-Michael; Weigel, Guenter; Quehenberger, Peter; Tomasits, Josef; Haushofer, Alexander C; Aspoeck, Gerold; Loacker, Lorin; Schnapka-Koepf, Mirjam; Goebel, Georg; Griesmacher, Andrea

    2012-01-01

    Dabigatran etexilate is a new oral anticoagulant for the therapy and prophylaxis of venous thromboembolism and stroke prevention in patients with atrial fibrillation. To investigate the extent of interactions of this new anticoagulant with frequently used coagulation assays, we completed a multicenter in vitro trial with Conformité Européenne(CE)-labeled dabigatran-spiked plasma samples. Lyophilized plasma samples with dabigatran concentrations ranging from 0.00 to 0.48 μg/mL were sent to the coagulation laboratories of six major Austrian hospitals for evaluation. Coagulation assays were performed under routine conditions using standard reagents and analyzer. Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. Even non-clotting tests, such as the colorimetric factor XIII activity assay and to a minor extent the amidolytic antithrombin activity assay (via factor IIa) were affected. This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.

  13. Activation of Nrf2 protects against triptolide-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Jia Li

    Full Text Available Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF, has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2 in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN, attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

  14. The climatic change induced by human activities

    International Nuclear Information System (INIS)

    Balairon Ruiz, L.

    2004-01-01

    The climate of the Earth is a changing climate. Along their history many natural climate changes have existed in all time scales. At the present time we use the term climate changes have existed in all time scales. At the present time we use the term climate change in a restricted way, understanding that we have referring to a singular change that has their origin in the modification of the natural composition of the atmosphere. The increase of greenhouse gases from the second half the XVIII century, is due to the human activities of fossil fuels burning to obtain energy and to industrial and agricultural activities needing for the development of a world which population has been duplicated between 1960 and 2000, until overcoming the 6,000 million inhabitants. In particular, the concentrations of carbon dioxide-CO 2 have increased in a 34%. The more recent emission scenarios proposed by the IPCC (SRES, 2000) are based on hypothesis about the population evolution, the energy consumption and the word patterns of development, which are grouped in four families dominated as A1, A2, B1 and B2. The answer for these scenarios from a range of climate models results in an increase of the world average surface atmospheric temperature between 1,4 degree centigrade and 5,8 degree centigrade and a corresponding sea level rise understood between 9 cm and 88 cm. The changes in the precipitation patterns show us that could be above to the current one in high and media latitudes and below in subtropical latitudes, with exceptions highly depending of the model used. (Author)

  15. How to manage new oral anticoagulants in case of surgery

    Directory of Open Access Journals (Sweden)

    Davide Imberti

    2013-12-01

    Full Text Available When a patient receiving new oral anticoagulants (NOACs requires an invasive procedure, the consequences of bleeding if anticoagulation is continued and the risk of thrombosis if it is omitted need to be carefully considered. In addition to the bleeding risk of the procedure, it is of paramount importance to evaluate the renal function, especially for dabigatran that is eliminated predominantly via the renal pathway. NOAC therapy should be stopped for at least 24 h before the intervention, and a longer interruption should be considered in cases of high bleeding risk procedures and/or renal failure. A base-line assessment of coagulation should be performed and intervention should be postponed (if possible if high levels of anticoagulation parameters are found. In the post-surgical period, if oral anticoagulant therapy cannot be re-started, patients should temporarily receive low molecular weight heparins and re-start NOACs as soon as possible.

  16. Do we have to anticoagulated patients with cerebral venous thrombosis?

    DEFF Research Database (Denmark)

    Feher, G; Illes, Z; Hargroves, D

    2016-01-01

    INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare form of venous thromboembolism (VTE). Although anticoagulation is recommended for the initial and long term treatment with regards to thrombotic risks for patients with CVT, the role of anticogalution has not been fully elucidated. The aim...... of our literature based review was collect articles showing the benefit of anticoagulation in CVT and gathering the data of follow-up studies focusing on the recurrence of CVT and other thrombotic events. RESULTS: We have identified 15 follow-up studies studies with 2422 patients . The mean duration...... of follow up was 37,9 months. Death occured in 6,5% and 76,4 % of the patients had favourable outcome. 85,5 % received initial anticoagulation with ultrafractionated or low molecular weight heparin and 82,1 % received long-term anticoagulation. Recurent CVT occured in 3,7% and other thrombotic event occured...

  17. [Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

    Science.gov (United States)

    del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

    2015-10-01

    New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  18. Generic switching of warfarin and risk of excessive anticoagulation

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard

    2016-01-01

    PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analys...

  19. Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

    African Journals Online (AJOL)

    : Anticoagulation, Barriers, Nigeria, .... Cardiovascular disease (thromboembolic stroke). 2/26 (7.7). Heart valve replacement. 2/26 (7.7) ... accounts for approximately 2% of the reported hemorrhagic complications of warfarin therapy and is ...

  20. Upper Airway Obstruction Secondary to Anticoagulant Rodenticide Toxicosis in Five Dogs.

    Science.gov (United States)

    Lawson, Corinne; O'Brien, Mauria; McMichael, Maureen

    Five dogs were presented with clinical signs compatible with upper airway obstruction, including stridor, stertor, coughing, gagging, and varying degrees of respiratory distress. All dogs had radiographic findings of soft tissue opacity in the area of the pharynx, larynx, or trachea, and several had narrowing of the tracheal lumen. Coagulation abnormalities (prolonged prothrombin time, activated partial thromboplastin time) were present in the four dogs that underwent testing. Four of five dogs were treated for the coagulopathy, presumably due to anticoagulant rodenticide toxicosis, and survived to discharge.Upper airway obstruction is an unusual presentation for anticoagulant rodenticide toxicosis in dogs. Raising the index of suspicion for this treatable condition may help clinicians to identify this sooner.

  1. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Gómez-Outes A

    2013-05-01

    and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin or once-weekly dosing (ie, idraparinux and idrabiotaparinux, as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban. In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.Keywords: anticoagulants, venous thromboembolism, cancer, dabigatran, apixaban, rivaroxaban

  2. Extractions without eliminating anticoagulant treatment : a literature review.

    OpenAIRE

    Rodríguez Cabrera, Manuel Alejandro; Barona Dorado, Cristina; Leco Berrocal, María Isabel; Gómez Moreno, Gerardo; Martínez González, José María

    2011-01-01

    To establish whether there is a high enough risk of bleeding in patients who take oral anticoagulants, such that it would justify not using oral anticoagulants when performing a dental extraction, as well as if the reason for and anatomical location of the extraction increases such risk. Study We performed a bibliographic search in order to carry out a meta-analytic study using descriptive statistics. We compiled a sample of 1194 patients from the articles selected. Of these patients, a total...

  3. [Risk and benefit of oral anticoagulants in atrial fibrillation].

    Science.gov (United States)

    Zotova, I V; Zateĭshchikov, D A

    2011-01-01

    Thromboembolism is the main cause of death and disability of patients with atrial fibrillation. Indirect anticoagulants are effective means of primary and secondary prevention of thromboembolic complications. However in a number of patients risk associated with therapy with indirect anticoagulants might exceed potential benefit. The principle problem requiring solution in a patient with atrial fibrillation is individual comparative assessment of risk of development of thromboembolic and hemorrhagic complications. Modern stratification scales which allow solving this problem are considered in this review.

  4. Lupus Anticoagulant and Anticardiolipin Antibodies in Unexplained Fetal Losses

    OpenAIRE

    ALPER, Gülinnaz

    2014-01-01

    Lupus anticoagulant (LA) and anti-cardiolipin antibodies (ACAs) are acquired antiphospholipid antibodies (APAs), which are considered to be important markers for pregnancy losses and intrauterine fetal demise. LA and ACAs have anticoagulant effects in vitro and thrombotic effects in vivo and are considered to be the cause of recur-rent pregnancy losses (RPLs), resulting from placental vascular thrombosis and infarction. The aim of this study was to identify the most sensitive and specific met...

  5. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  6. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  7. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    International Nuclear Information System (INIS)

    Meng, Zhen; Gan, Ye-Hua

    2015-01-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN

  8. [Perioperative management of direct oral anticoagulant in emergency surgery and bleeding. Haemostasis monitoring and treatment].

    Science.gov (United States)

    Hidalgo, F; Gómez-Luque, A; Ferrandis, R; Llau, J V; de Andrés, J; Gomar, C; Sierra, P; Castillo, J; Torres, L M

    2015-10-01

    There is an almost unanimous consensus on the management of the direct new oral anticoagulants, dabigatran, rivaroxaban, and apixaban in elective surgery. However, this general consensus does not exist in relation with the direct new oral anticoagulants use in emergency surgery, especially in the bleeding patient. For this reason, a literature review was performed using the MEDLINE-PubMed. An analysis was made of the journal articles, reviews, systematic reviews, and practices guidelines published between 2000 and 2014 using the terms "monitoring" and "reversal". From this review, it was shown that the routine tests of blood coagulation, such as the prothrombin time and activated partial thromboplastin time, have a limited efficacy in the perioperative control of blood coagulation in these patients. There is currently no antidote to reverse the effects of these drugs, although the possibility of using concentrated prothrombin complex and recombinant activated factor vii has been suggested for the urgent reversal of the anticoagulant effect. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Aldehyde-induced xanthine oxidase activity in raw milk.

    Science.gov (United States)

    Steffensen, Charlotte L; Andersen, Henrik J; Nielsen, Jacob H

    2002-12-04

    In the present study, the aldehyde-induced pro-oxidative activity of xanthine oxidase was followed in an accelerated raw milk system using spin-trap electron spin resonance (ESR) spectroscopy. The aldehydes acetaldehyde, propanal, hexanal, trans-2-hexenal, trans-2-heptenal, trans-2-nonenal, and 3-methyl-2-butenal were all found to initiate radical reactions when added to milk. Formation of superoxide through aldehyde-induced xanthine oxidase activity is suggested as the initial reaction, as all tested aldehydes were shown to trigger superoxide formation in an ultrahigh temperature (UHT) milk model system with added xanthine oxidase. It was found that addition of aldehydes to milk initially increased the ascorbyl radical concentration with a subsequent decay due to ascorbate depletion, which renders the formation of superoxide in milk with added aldehyde. The present study shows for the first time potential acceleration of oxidative events in milk through aldehyde-induced xanthine oxidase activity.

  10. Pulsed electric field extraction enhanced anti-coagulant effect of fungal polysaccharide from Jew's ear (Auricularia auricula).

    Science.gov (United States)

    Li, Changtian; Mao, Xinxin; Xu, Baojun

    2013-01-01

    As a Chinese herbal medicine, Jew's ear has been known for its anti-coagulant effects. Hence it is worthwhile developing an effective technique to extract active components. To find the optimal extraction condition and to identify the best strain to yield fungal polysaccharide with anti-coagulant activity. Three strains of Jew's ear from Jilin Province, named as 988, DY 18 and FS 02, and three extraction techniques, namely, high intensity pulsed electric fields (HIPEF), microwave-assisted extraction method (MAEM) and ultrasonic-assisted extraction method (UAEM), were applied to optimise the extraction conditions. The crude extracts and polysaccharides were further determined for anti-coagulant activities. All extracts prolonged blood clotting time as compared to reagent control. The HIPEF exhibited the most remarkable effect among the three extraction techniques. The anti-coagulant activities of extracts were enhanced with increasing electric field strength when the field strength reached 24 kV/cm. Current results suggest that the HIPEF technique will be an effective method in the manufacture of bioactive natural polysaccharide. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis

    NARCIS (Netherlands)

    Wildt, William de; Kooijman, Huub; Funke, Carel; Üstün, Bülent; Leika, Afranina; Lunenburg, Maarten; Kaspersen, Frans; Kellenbach, Edwin

    2017-01-01

    Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra(®). The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming

  12. Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate

    Directory of Open Access Journals (Sweden)

    L Bellamy

    2009-07-01

    Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran

  13. Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Werb, Z.; Aggeler, J.

    1978-04-01

    We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.

  14. Anticoagulant-free Genius haemodialysis using low molecular weight heparin-coated circuits.

    Science.gov (United States)

    Frank, Rolf Dario; Müller, Ute; Lanzmich, Regina; Groeger, Christian; Floege, Jürgen

    2006-04-01

    Regional citrate anticoagulation or saline flushes are often used in haemodialysis patients at high risk of bleeding. In an alternative approach we evaluated the effects of covalent circuit coating with low molecular weight heparin (LMWH) for intermittent haemodialysis. In vitro, we compared the thrombogenicity of an uncoated polyvinylchloride (PVC) tubing set with LMWH-coated tubing (AOThel) and a reference tubing with end-point attached heparin coating (Carmeda Bioactive surface) under dynamic blood contact. In vivo, five chronic haemodialysis patients were studied using the Genius dialysis system and F60S filters. Each patient underwent three dialysis sessions separated by a standard haemodialysis each: (1) standard dialysis (uncoated circuit and regular dalteparin dosage), (2) dialysis with LMWH-coated circuit and regular dalteparin dosage and (3) dialysis with a completely LMWH-coated circuit without anticoagulant use. In vitro, both coated tubings showed significantly reduced thrombin-antithrombin (TAT) complex levels compared with PVC. The reference coating (Carmeda) released substantial antifactor Xa (antiXa) activity into the plasma. The LMWH coating (AOThel) released low antiXa activity only during the initial rinsing. In vivo, all dialysis sessions were well tolerated and completed without major clotting. Antithrombin levels and platelet counts were similar in all groups. P-selectin and D-dimer levels increased similarly in all groups. TAT levels were comparable in all groups during the first 3 h and significantly increased in the anticoagulant-free group after the fourth hour. LMWH surface coating reduces thrombogenicity in vitro without releasing significant amounts of heparin from the surface. In vivo, anticoagulant-free haemodialysis using a completely LMWH-coated circuit is feasible and safe in stable chronic dialysis patients with normal coagulation.

  15. [Progress of anticoagulation therapy in atrial fibrillation].

    Science.gov (United States)

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-07

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. Novel oral anticoagulants in acute coronary syndrome.

    Science.gov (United States)

    Costopoulos, Charis; Niespialowska-Steuden, Maria; Kukreja, Neville; Gorog, Diana A

    2013-09-10

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide with a prevalence that has now reached pandemic levels as a consequence of the rapid modernization of the developing world. Its presentation as an acute coronary syndrome (ACS) is a frequent reason for hospital admission and of profound implications for personal, societal and global health. Despite improvements in the management of ACS with anti-platelet and anticoagulant therapy and revascularization techniques, many patients continue to suffer recurrent ischemic events. The need to reduce future cardiovascular events has led to the development of novel therapies to prevent coronary thrombosis, targeting thrombin-mediated pathways. These include direct Xa inhibitors (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran) and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews the comparative mechanisms of action, the risks and benefits, together with the clinical evidence base for the use of these novel oral agents in the management of ACS patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Stav Sapoznik

    2016-02-01

    Full Text Available In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.

  18. Shock-induced electrical activity in polymeric solids. A mechanically induced bond scission model

    International Nuclear Information System (INIS)

    Graham, R.A.

    1979-01-01

    When polymeric solids are subjected to high-pressure shock loading, two anomalous electrical phenomena, shock-induced conduction and shock-induced polarization, are observed. The present paper proposes a model of mechanically induced bond scission within the shock front to account for the effects. An experimental study of shock-induced polarization in poly(pyromellitimide) (Vespel SP-1) is reported for shock compressions from 17 to 23% (pressures from 2.5 to 5.4 GPa). Poly(pyromellitimide) is found to be a strong generator of such polarization and the polarization is found to reflect an irreversible or highly hysteretic process. The present measurements are combined with prior measurements to establish a correlation between monomer structure and strength of shock-induced polarization; feeble signals are observed in the simpler monomer repeat units of poly(tetrafluoroethylene) and polyethylene while the strongest signals are observed in more complex monomers of poly(methyl methacrylate) and poly(pyromellitimide). It is also noted that there is an apparent correlation between shock-induced conduction and shock-induced polarization. Such shock-induced electrical activity is also found to be well correlated with the propensity for mechanical bond scission observed in experiments carried out in conventional mechanochemical studies. The bond scission model can account for characteristics observed for electrical activity in shock-loaded polymers and their correlation to monomer structure. Localization of elastic energy within the monomer repeat unit or along the main chain leads to the different propensities for bond scission and resulting shock-induced electrical activity

  19. Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

    Science.gov (United States)

    Livnat, Tami; Zivelin, Ariella; Tamarin, Ilia; Guetta, Victor; Salomon, Ophira

    2009-12-01

    Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.

  20. Pharmacy students provide care comparable to pharmacists in an outpatient anticoagulation setting.

    Science.gov (United States)

    Dalal, Kavita; McCall, Kenneth L; Fike, David S; Horton, Niambi; Allen, April

    2010-10-11

    To evaluate whether student participation in ambulatory clinics influenced the percentage of therapeutic international normalized ratio (INR) results among patients on chronic warfarin therapy. Medical records in outpatient anticoagulation clinics managed by pharmacists under physician protocol were reviewed retrospectively in 2 university-affiliated clinics in Amarillo and Lubbock, TX. Pharmacy student activities included patient interviews, vital sign measurements, fingersticks, counseling, and documentation. Patient visits were conducted by a precepted pharmacy student or a pharmacist without a student, and the INR was measured at the subsequent patient visit. Records of 1,958 anticoagulation patient visits were reviewed; 865 patients were treated by pharmacists, and 1093 were treated by precepted students. The follow-up INR was therapeutic for 48.5% of third-year (P3) students' patients, 45.6% of fourth-year (P4) students' patients, 51.2% of residents' patients, and 44.7% of pharmacists's patients (p = 0.23). Eight variables were associated with the follow-up INR (baseline INR, warfarin noncompliance, held warfarin doses, a warfarin dosage adjustment, diet change, alcohol use, tobacco use, and any medication changes). Student participation in the patient-care process did not compromise patient care and no significant difference in patient outcomes was found between patients in an anticoagulation clinic cared for by precepted students and those cared for by pharmacists.

  1. Do novel oral anticoagulants do better than standard therapy in the treatment of deep vein thrombosis?

    Science.gov (United States)

    Brodmann, M

    2013-08-01

    The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor.

  2. Code ACTIVE for calculation of the transmutation, induced activity and decay heat in neutron irradiation

    International Nuclear Information System (INIS)

    Ioki, Kimihiro; Harada, Yuhei; Asami, Naoto.

    1976-03-01

    The computer code ACTIVE has been prepared for calculation of the transmutation rate, induced activity and decay heat. Calculations are carried out with activation chain and spatial distribution of neutron energy spectrum. The spatial distribution of secondary gamma-ray source due to the unstable nuclides is also obtainable. Special attension is paid to the short life decays. (auth.)

  3. Influence of jasmonic acid as potential activator of induced ...

    Indian Academy of Sciences (India)

    MADU

    resistant and susceptible varieties under the influence of JA. Thus, exogenously applied ... [Mandal M K, Pandey D, Purwar S, Singh U S and Kumar A 2006 Influence of jasmonic acid as potential activator of induced resistance against. Karnal bunt in developing ...... expression; Trends Plant Sci. 2 302–307. MS received 7 ...

  4. Cellulase activity of filamentous fungi induced by rice husk | Oliveros ...

    African Journals Online (AJOL)

    Cellulase activity of filamentous fungi induced by rice husk. DF Oliveros, N Guarnizo, EM Perea, WM Arango. Abstract. The objective of this study was to determine the potential of different filamentous fungi to degrade cellulose in rice husk pre-treated with steam explosion or alkaline hydrolysis. A preliminary test performed ...

  5. Reducing friction-induced vibration using intelligent active force ...

    Indian Academy of Sciences (India)

    In this paper, a novel approach to reduce the effect of mode coupling that causes friction induced vibration (FIV) is proposed by applying an intelligent active force control (AFC)-based strategy employing piezoelectric actuators with hysteresis effect to a simplified two degree-of-freedom mathematical model of a ...

  6. Influence of jasmonic acid as potential activator of induced ...

    Indian Academy of Sciences (India)

    MADU

    Influence of jasmonic acid as potential activator of induced resistance against Karnal bunt in developing spikes of wheat. MIHIR K MANDAL, DINESH PANDEY, SHALINI PURWAR, U S SINGH* and ANIL KUMAR. †. Department of Molecular Biology and Genetic Engineering, College of Basic Sciences and Humanities, ...

  7. Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Sjøland, Jonas A.; Gram, Jørgen

    2007-01-01

    OBJECTIVE: Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL) are suggested as risk factors for development of deep vein thrombosis (DVT) among patients without systemic lupus erythematosus (SLE). Other conditions, e.g. inflammation, are reported to induce LA and it is uncertain whether...... the association between LA and DVT is causal. In this study the associations between aPL, LA and inflammation were investigated in 170 consecutive patients without SLE, but with a tentative diagnosis of DVT. MATERIAL AND METHODS: DVT was diagnosed in 64 patients. LA was determined according to the criteria...

  8. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Directory of Open Access Journals (Sweden)

    Tongfang Tang

    Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  9. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Science.gov (United States)

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  10. No influence of dabigatran anticoagulation on hemorrhagic transformation in an experimental model of ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Ferdinand Bohmann

    Full Text Available BACKGROUND: Dabigatran etexilate (DE is a new oral direct thrombin inhibitor. Clinical trials point towards a favourable risk-to-benefit profile of DE compared to warfarin. In this study, we evaluated whether hemorrhagic transformation (HT occurs after experimental stroke under DE treatment as we have shown for warfarin. METHODS: 44 male C57BL/6 mice were pretreated orally with 37.5 mg/kg DE, 75 mg/kg DE or saline and diluted thrombin time (dTT and DE plasma concentrations were monitored. Ischemic stroke was induced by transient middle cerebral artery occlusion (tMCAO for 1 h or 3 h. We assessed functional outcome and HT blood volume 24 h and 72 h after tMCAO. RESULTS: After 1 h tMCAO, HT blood volume did not differ significantly between mice pretreated with DE 37.5 mg/kg and controls (1.5±0.5 µl vs. 1.8±0.5 µl, p>0.05. After 3 h tMCAO, DE-anticoagulated mice did also not show an increase in HT, neither at the dose of 37.5 mg/kg equivalent to anticoagulant treatment in the therapeutic range (1.3±0.9 µl vs. control 2.3±0.5 µl, p>0.05 nor at 75 mg/kg, clearly representing supratherapeutic anticoagulation (1.8±0.8 µl, p>0.05. Furthermore, no significant increase in HT under continued anticoagulation with DE 75 mg/kg could be found at 72 h after tMCAO for 1 h (1.7±0.9 µl vs. control 1.6±0.4 µl, p>0.05. CONCLUSION: Our experimental data suggest that DE does not significantly increase hemorrhagic transformation after transient focal cerebral ischemia in mice. From a translational viewpoint, this indicates that a continuation of DE anticoagulation in case of an ischemic stroke might be safe, but clearly, clinical data on this question are warranted.

  11. Thrombin-Inhibiting Anticoagulant Liposomes: Development and Characterization.

    Science.gov (United States)

    Endreas, Wegderes; Brüßler, Jana; Vornicescu, Doru; Keusgen, Michael; Bakowsky, Udo; Steinmetzer, Torsten

    2016-02-04

    Many peptides and peptidomimetic drugs suffer from rapid clearance in vivo; this can be reduced by increasing their size through oligomerization or covalent conjugation with polymers. As proof of principle, an alternative strategy for drug oligomerization is described, in which peptidomimetic thrombin inhibitors are incorporated into the liposome surface. For this purpose, the inhibitor moieties were covalently coupled to a palmitic acid residue through a short bifunctionalized ethylene glycol spacer. These molecules were directly added to the lipid mixture used for liposome preparation. The obtained liposomes possess strong thrombin inhibitory potency in enzyme kinetic measurements and anticoagulant activity in plasma. Their strong potency and positive ζ potential indicate that large amounts of the benzamidine-derived inhibitors are located on the surface of the liposomes. This concept should be applicable to other drug molecules that suffer from rapid elimination and allow covalent modification with a suitable fatty acid residue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Neurotoxic reactive astrocytes are induced by activated microglia.

    Science.gov (United States)

    Liddelow, Shane A; Guttenplan, Kevin A; Clarke, Laura E; Bennett, Frederick C; Bohlen, Christopher J; Schirmer, Lucas; Bennett, Mariko L; Münch, Alexandra E; Chung, Won-Suk; Peterson, Todd C; Wilton, Daniel K; Frouin, Arnaud; Napier, Brooke A; Panicker, Nikhil; Kumar, Manoj; Buckwalter, Marion S; Rowitch, David H; Dawson, Valina L; Dawson, Ted M; Stevens, Beth; Barres, Ben A

    2017-01-26

    Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases.

  13. Antimicrobial Activity of UV-Induced Phenylamides from Rice Leaves

    Directory of Open Access Journals (Sweden)

    Hye Lin Park

    2014-11-01

    Full Text Available Rice produces a wide array of phytoalexins in response to pathogen attacks and UV-irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from UV-treated rice leaves showed that several phenolic compounds in addition to sakuranetin accumulated remarkably in rice leaves. We isolated two compounds from UV-treated rice leaves using silica gel column chromatography and preparative HPLC. The isolated phenolic compounds were identified as phenylamide compounds: N-trans-cinnamoyltryptamine and N-p-coumaroylserotonin. Expression analysis of biosynthetic genes demonstrated that genes for arylamine biosynthesis were upregulated by UV irradiation. This result suggested that phenylamide biosynthetic pathways are activated in rice leaves by UV treatment. To unravel the role of UV-induced phenylamides as phytoalexins, we examined their antimicrobial activity against rice fungal and bacterial pathogens. N-trans-Cinnamoyltryptamine inhibited the growth of rice brown spot fungus (Bipolaris oryzae. In addition to the known antifungal activity to the blast fungus, sakuranetin had antimicrobial activity toward B. oryzae and Rhizoctonia solani (rice sheath blight fungus. UV-induced phenylamides and sakuranetin also had antimicrobial activity against rice bacterial pathogens for grain rot (Burkholderia glumae, blight (Xanthomonas oryzae pv. oryzae and leaf streak (X. oryzae pv. oryzicola diseases. These findings suggested that the UV-induced phenylamides in rice are phytoalexins against a diverse array of pathogens.

  14. Enhanced stimulus-induced gamma activity in humans during propofol-induced sedation.

    Directory of Open Access Journals (Sweden)

    Neeraj Saxena

    Full Text Available Stimulus-induced gamma oscillations in the 30-80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

  15. Nrf2 activation prevents cadmium-induced acute liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  16. A comparative study of antithrombotic and antiplatelet activities of different fucoidans from Laminaria japonica.

    Science.gov (United States)

    Zhao, Xue; Dong, Shizhu; Wang, Jingfeng; Li, Fang; Chen, Anjin; Li, Bafang

    2012-06-01

    Fucoidans extracted from brown algae represent an intriguing group of natural fucose-enriched sulfated polysaccharide, with excellent anticoagulant, antimetastatic, antiangiogenic and anti-inflammatory activities. In the present study, we compared antithrombotic activities of four fucoidan fractions with different molecular weight and sulfated ester content from Laminaria japonica in an electrical induced arterial thrombosis and their potential mechanism underlying such activity. In vivo middle molecular weight (MMW) fucoidan fractions with molecular weight about 28000 and 35000 exhibited better antithrombotic activity in electrical induced arterial thrombosis than low molecular weight (LMW) fucoidan LF1 and LF2 (Mw 7600 and 3900). Inhibition of arterial thrombosis occurred at dose of 0.1-0.25mg/kg for MMW fucoidans, accompanied with moderate anticoagulant activity and significant decrease of whole blood viscosity and hematocrit. The antithrombotic effects of MMW Fucoidans might be related with promotion of TFPI content and decrease of TXB2 content, without affecting platelet aggregation and 6-keto-PGF1α content in vivo. In contrast, LMW fucoidans showed a correlation among anticoagulant, antiplatelet and antithrombotic effects in vivo. Antithrombotic action of LF1 and LF2 required high dose of 2.5-10mg/kg, concomitantly with anticoagulant activity and specific inhibition of platelet aggregation in vivo. Their antithrombotic effect might be related to their promotion of TFPI and 6-keto-PGF1α, down regulation of TXB2, without affecting hemorheology. These findings suggested that fucoidan fractions with different molecular weight acted on the antithrombotic action by different mechanism. By comparison, highly sulfated fucoidan LF2 with molecular weight of 3900 seemed to be a more suitable choice of antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic

  17. Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis

    Science.gov (United States)

    HajMohammadi, Sassan; Enjyoji, Keiichi; Princivalle, Marc; Christi, Patricia; Lech, Miroslav; Beeler, David; Rayburn, Helen; Schwartz, John J.; Barzegar, Samad; de Agostini, Ariane I.; Post, Mark J.; Rosenberg, Robert D.; Shworak, Nicholas W.

    2003-01-01

    Endothelial cell production of anticoagulant heparan sulfate (HSact) is controlled by the Hs3st1 gene, which encodes the rate-limiting enzyme heparan sulfate 3-O-sulfotransferase-1 (3-OST-1). In vitro, HSact dramatically enhances the neutralization of coagulation proteases by antithrombin. The in vivo role of HSact was evaluated by generating Hs3st1–/– knockout mice. Hs3st1–/– animals were devoid of 3-OST-1 enzyme activity in plasma and tissue extracts. Nulls showed dramatic reductions in tissue levels of HSact but maintained wild-type levels of tissue fibrin accumulation under both normoxic and hypoxic conditions. Given that vascular HSact predominantly occurs in the subendothelial matrix, mice were subjected to a carotid artery injury assay in which ferric chloride administration induces de-endothelialization and occlusive thrombosis. Hs3st1–/– and Hs3st1+/+ mice yielded indistinguishable occlusion times and comparable levels of thrombin•antithrombin complexes. Thus, Hs3st1–/– mice did not show an obvious procoagulant phenotype. Instead, Hs3st1–/– mice exhibited genetic background–specific lethality and intrauterine growth retardation, without evidence of a gross coagulopathy. Our results demonstrate that the 3-OST-1 enzyme produces the majority of tissue HSact. Surprisingly, this bulk of HSact is not essential for normal hemostasis in mice. Instead, 3-OST-1–deficient mice exhibited unanticipated phenotypes suggesting that HSact or additional 3-OST-1–derived structures may serve alternate biologic roles. PMID:12671048

  18. Obesity-induced vascular inflammation involves elevated arginase activity.

    Science.gov (United States)

    Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

    2017-11-01

    Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-( S )-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

  19. Extractions without eliminating anticoagulant treatment: a literature review.

    Science.gov (United States)

    Rodríguez-Cabrera, Manuel-Alejandro; Barona-Dorado, Cristina; Leco-Berrocal, Isabel; Gómez-Moreno, Gerardo; Martínez-González, José-Maria

    2011-09-01

    To establish whether there is a high enough risk of bleeding in patients who take oral anticoagulants, such that it would justify not using oral anticoagulants when performing a dental extraction, as well as if the reason for and anatomical location of the extraction increases such risk. We performed a bibliographic search in order to carry out a meta-analytic study using descriptive statistics. We compiled a sample of 1194 patients from the articles selected. Of these patients, a total of 2392 simple, serial surgical extractions were performed; none of the patients interrupted their anticoagulant treatment with warfarin sodium. Of the sample, 83 patients presented a certain degree of bleeding; in 77 of such cases, the bleeding was controlled with local hemostasis, whereas 6 patients required their dose of oral anticoagulants to be adjusted. There was a higher incidence of bleeding in patients presenting a periodontal pathology, compared to deep caries and pericoronitis. Patients being treated with oral anticoagulants represent a risk that we should be aware of, but local hemostasis has proven to be effective when performing extractions, provided that the INR value is less than 4. There is an increased incidence of bleeding in patients with periodontal problems, due to the greater presence of inflammation in the soft tissues. If the extraction is performed in the maxilla, the incidence of hemorrhagic complications is slightly higher than in the mandible, although this difference is considered to be insignificant.

  20. Anticoagulants for the prevention and treatment of catheter-related thrombosis in adults and children on parenteral nutrition: a systematic review and critical appraisal.

    Science.gov (United States)

    Barco, Stefano; Atema, Jasper J; Coppens, Michiel; Serlie, Mireille J; Middeldorp, Saskia

    2017-07-01

    Patients on parenteral nutrition require a central venous access and are at risk of catheter-related thrombosis, pulmonary embolism, and vena cava syndrome. Parenteral nutrition guidelines suggest anticoagulation for the primary prevention of catheter-related thrombosis during long-term parenteral nutrition. We conducted a systematic review of the efficacy, safety and feasibility of anticoagulant use for preventing and treating catheter-related thrombosis during parenteral nutrition. We searched for interventional and observational studies on adults and children receiving systemic anticoagulants during either short- or long-term parenteral nutrition delivered via central venous access. Primary outcomes were: objectively-confirmed catheter-related thrombosis, pulmonary embolism and bleeding. Secondary outcomes were: heparin-induced thrombocytopenia, prevalence of anticoagulation, and quality of International Normalised Ratio management in vitamin K antagonist-treated patients. We identified 1,199 studies, of which 23 were included. Seven interventional studies of short-term parenteral nutrition (adult population, n=5) were classified as low-quality: in those, intravenous unfractionated heparin did not prevent catheter-related thrombosis if compared to saline. No interventional studies were conducted in patients on long-term parenteral nutrition. Observational data were sparse, rarely focusing on anticoagulation, and overall of low quality. The reported use of anticoagulants was between 22 and 66% in recent multicentre cohorts. The amount and quality of data in this area are very suboptimal: most studies are outdated and involved heterogeneous populations. Currently, there is insufficient evidence to allow conclusions to be reached regarding the efficacy and safety of anticoagulants in this setting.

  1. Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Luger S

    2015-11-01

    Full Text Available Sebastian Luger,1 Carina Hohmann,2 Daniela Niemann,1 Peter Kraft,3 Ignaz Gunreben,3 Tobias Neumann-Haefelin,2 Christoph Kleinschnitz,3 Helmuth Steinmetz,1 Christian Foerch,1 Waltraud Pfeilschifter1 1Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, 2Department of Neurology, Klinikum Fulda gAG, Fulda, 3Department of Neurology, University Hospital Würzburg, Würzburg, Germany Background: Oral anticoagulant therapy (OAT potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209. A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243 with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90% and patients

  2. The influence of experimentally induced pain on shoulder muscle activity.

    Science.gov (United States)

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul; Krogsgaard, Michael R; Nørregaard, Jesper

    2009-04-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0 degrees -105 degrees) at a speed of approximately 120 degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load

  3. Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

    Science.gov (United States)

    Ishihara, Yasuhiro; Takemoto, Takuya; Itoh, Kouichi; Ishida, Atsuhiko; Yamazaki, Takeshi

    2015-01-01

    Microglia are activated quickly in response to external pathogens or cell debris and clear these substances via the inflammatory response. However, excessive activation of microglia can be harmful to host cells due to the increased production of reactive oxygen species and proinflammatory cytokines. Superoxide dismutase 2 (SOD2) is reportedly induced under various inflammatory conditions in the central nervous system. We herein demonstrated that activated microglia strongly express SOD2 and examined the role of SOD2, focusing on regulation of the microglial activity and the susceptibility of microglia to oxidative stress. When rat primary microglia were treated with LPS, poly(I:C), peptidoglycan, or CpG oligodeoxynucleotide, respectively, the mRNA and protein levels of SOD2 largely increased. However, an increased expression of SOD2 was not detected in the primary neurons or astrocytes, indicating that SOD2 is specifically induced in microglia under inflammatory conditions. The activated microglia showed high tolerance to oxidative stress, whereas SOD2 knockdown conferred vulnerability to oxidative stress. Interestingly, the production of proinflammatory cytokines was increased in the activated microglia treated with SOD2 siRNA compared with that observed in the control siRNA-treated cells. Pretreatment with NADPH oxidase inhibitors, diphenylene iodonium and apocynin, decreased in not only reactive oxygen species generation but also the proinflammatory cytokine expression. Notably, SOD2 knockdown largely potentiated the nuclear factor κB activity in the activated microglia. Taken together, increased SOD2 conferred tolerance to oxidative stress in the microglia and decreased proinflammatory cytokine production by attenuating the nuclear factor κB activity. Therefore, SOD2 might regulate neuroinflammation by controlling the microglial activities. PMID:26231211

  4. Extended anticoagulation in venous thromboembolism disease. In favour.

    Science.gov (United States)

    Fernández Capitan, M C

    Venous thromboembolism disease can be considered a chronic disease because, after the first episode, there is a life-long risk of recurrence. Recurrence is a severe complication. Anticoagulation is effective while it is maintained, but when it is discontinued, the risk of new thrombotic events persists indefinitely. Clinical practice guidelines offer specific recommendations on the treatment duration for patients with provoked or recurrent disease but are not specific for those with a first unprovoked episode. The decision should be made after a careful individual assessment of the risk-benefit of anticoagulation. This article reviews the evidence in favour of extending the anticoagulation and the current therapeutic options. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  5. [Tranexamic acid gel in patients treated with oral anticoagulants].

    Science.gov (United States)

    Ripollés-de Ramón, Jorge; Muñoz-Corcuera, Marta; Bravo-Llatas, Carmen; Bascones-Martínez, Antonio

    2014-12-09

    Patients treated with oral anticoagulants have increased susceptibility to bleeding, and therefore any surgical medical procedure and especially oral surgery requires a therapeutic approach that minimizes bleeding effects in these patients. The working hypothesis was based on studies of local application of tranexamic acid after maxillofacial interventions as effective therapeutic alternative for the prevention and control of bleeding. The aim was to assess the effectiveness of the application of a gel solution tranexamic acid after tooth extraction in anticoagulated patients in terms of healing time and degree of healing. The results indicate that application of tranexamic acid gel is very effective for consistency and maintenance in the place of action and shows its efficacy as a procoagulant material. The application of a gel solution of tranexamic acid in oral anticoagulants patients ameliorates healing time and the bleeding time within the first 48-72 h. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  6. [Novel anticoagulants for stroke prevention in atrial fibrillation].

    Science.gov (United States)

    Baumhäkel, M; Schirmer, S H; Böhm, M

    2010-11-01

    The most frequent cardiac arrhythmia and main cause for cardio-embolic stroke is atrial fibrillation. Prophylaxis for thrombembolic events is performed regarding individual risk of patients with either ASS or vitamin-K-antagonists. Efficacy and safety of oral anticoagulation is limited by a narrow therapeutical range as well as by inter- and intraindividual variability of INR-values due to genetic disposition, differences in alimentation, dosage errors, rare control of INR-levels and drug-interactions. New oral anticoagulants with different mechanisms of action may be a promising therapeutic option in future. This review addresses the new anticoagulants Apixaban, Rivaroxban and Dabigatranetexilat with the design and as available the results of the corresponding phase-III-trials in atrial fibrillation (ARISTOTLE, ROCKET-AF, RE-LY). © Georg Thieme Verlag KG Stuttgart · New York.

  7. Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice.

    Science.gov (United States)

    Flaker, Greg C; Theriot, Paul; Binder, Lea G; Dobesh, Paul P; Cuker, Adam; Doherty, John U

    2016-07-12

    Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Mechanical Prosthetic Valves and Pregnancy: A therapeutic dilemma of anticoagulation

    Directory of Open Access Journals (Sweden)

    Prashanth Panduranga

    2014-10-01

    Full Text Available Choosing the best anticoagulant therapy for a pregnant patient with a mechanical prosthetic valve is controversial and the published international guidelines contain no clear-cut consensus on the best approach. This is due to the fact that there is presently no anticoagulant which can reliably decrease thromboembolic events while avoiding damage to the fetus. Current treatments include either continuing oral warfarin or substituting warfarin for subcutaneous unfractionated heparin or low-molecular-weight heparin (LMWH in the first trimester (6–12 weeks or at any point throughout the pregnancy. However, LMWH, while widely-prescribed, requires close monitoring of the blood anti-factor Xa levels. Unfortunately, facilities for such monitoring are not universally available, such as within hospitals in developing countries. This review evaluates the leading international guidelines concerning anticoagulant therapy in pregnant patients with mechanical prosthetic valves as well as proposing a simplified guideline which may be more relevant to hospitals in this region.

  9. Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Xuan Fu

    2008-04-01

    Full Text Available DNA damage such as double-stranded DNA breaks (DSBs has been reported to stimulate mitochondrial biogenesis. However, the underlying mechanism is poorly understood. The major player in response to DSBs is ATM (ataxia telangiectasia mutated. Upon sensing DSBs, ATM is activated through autophosphorylation and phosphorylates a number of substrates for DNA repair, cell cycle regulation and apoptosis. ATM has been reported to phosphorylate the alpha subunit of AMP-activated protein kinase (AMPK, which senses AMP/ATP ratio in cells, and can be activated by upstream kinases. Here we provide evidence for a novel role of ATM in mitochondrial biogenesis through AMPK activation in response to etoposide-induced DNA damage.Three pairs of human ATM+ and ATM- cells were employed. Cells treated with etoposide exhibited an ATM-dependent increase in mitochondrial mass as measured by 10-N-Nonyl-Acridine Orange and MitoTracker Green FM staining, as well as an increase in mitochondrial DNA content. In addition, the expression of several known mitochondrial biogenesis regulators such as the major mitochondrial transcription factor NRF-1, PGC-1alpha and TFAM was also elevated in response to etoposide treatment as monitored by RT-PCR. Three pieces of evidence suggest that etoposide-induced mitochondrial biogenesis is due to ATM-dependent activation of AMPK. First, etoposide induced ATM-dependent phosphorylation of AMPK alpha subunit at Thr172, indicative of AMPK activation. Second, inhibition of AMPK blocked etoposide-induced mitochondrial biogenesis. Third, activation of AMPK by AICAR (an AMP analogue stimulated mitochondrial biogenesis in an ATM-dependent manner, suggesting that ATM may be an upstream kinase of AMPK in the mitochondrial biogenesis pathway.These results suggest that activation of ATM by etoposide can lead to mitochondrial biogenesis through AMPK activation. We propose that ATM-dependent mitochondrial biogenesis may play a role in DNA damage response

  10. Sugarwin: a sugarcane insect-induced gene with antipathogenic activity.

    Science.gov (United States)

    Medeiros, Ane H; Franco, Flávia P; Matos, Juliana L; de Castro, Patrícia A; Santos-Silva, Ludier K; Henrique-Silva, Flávio; Goldman, Gustavo H; Moura, Daniel S; Silva-Filho, Marcio C

    2012-05-01

    In sugarcane fields, colonization of the stalk by opportunistic fungi usually occurs after the caterpillar Diatraea saccharalis attacks the sugarcane plant. Plants respond to insect attack by inducing and accumulating a large set of defense proteins. Two homologues of a barley wound-inducible protein (BARWIN), sugarcane wound-inducible proteins SUGARWIN1 and SUGARWIN2, have been identified in sugarcane by an in silico analysis. Antifungal properties have been described for a number of BARWIN homologues. We report that a SUGARWIN::green fluorescent protein fusion protein is located in the endoplasmic reticulum and in the extracellular space of sugarcane plants. The induction of sugarwin transcripts occurs in response to mechanical wounding, D. saccharalis damage, and methyl jasmonate treatment. The accumulation of transcripts is late induced and is restricted to the site of the wound. Although the transcripts of sugarwin genes were strongly increased following insect attack, the protein itself did not show any effect on insect development; rather, it altered fungal morphology, leading to the apoptosis of the germlings. These results suggest that, in the course of evolution, sugarwin-encoding genes were recruited by sugarcane due to their antipathogenic activity. We rationalize that sugarcane is able to induce sugarwin gene expression in response to D. saccharalis feeding as a concerted plant response to the anticipated invasion by the fungi that typically penetrate the plant stalk after insect damage.

  11. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees...... that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation...

  12. Calculation of induced activity in the V-230 reactor

    International Nuclear Information System (INIS)

    Bouhahhane, A.; Farkas, G.

    2013-01-01

    In this paper, we focused on the calculation of the neutron induced activity of nuclear reactor components for decommissioning purposes. The results confirm, that the most important radionuclides in the reactor components dismantling process are 55 Fe (1 st decade), 60 Co (10 - 50 y) and 63 Ni (during the whole process). Another aim of this paper was to refer to the possibility to improve the accuracy of the calculations using continuous energy Monte Carlo methods. (authors)

  13. Soybean Extract Antioxidant Protective Activity Against Copper-Induced Cytotoxicity

    OpenAIRE

    Mansour I. Almansour

    2008-01-01

    The antioxidant activity of soybean crude extract against induced oxidative damage has been achieved through quails Coturnix coturnix treatment with various copper sulphate concentrations alone or with a protective dose of soybean crude extract. Several parameters of oxidative stress together with liver and kidney function tests in serum and liver tissue homogenate were studied. Hematologic indices and liver copper content were determined. Obtained data showed a significant increase in...

  14. Differences in patient outcomes and chronic care management of oral anticoagulant therapy: an explorative study

    NARCIS (Netherlands)

    Drewes, H.W.; Lambooij, M.S.; Baan, C.A.; Meijboom, B.R.; Graafmans, W.C.; Westert, G.P.

    2011-01-01

    BACKGROUND: The oral anticoagulant therapy - provided to prevent thrombosis - is known to be associated with substantial avoidable hospitalization. Improving the quality of the oral anticoagulant therapy could avoid drug related hospitalizations. Therefore, this study compared the patient outcomes

  15. Differences in patient outcomes and chronic care management of oral anticoagulant therapy : An explorative study

    NARCIS (Netherlands)

    Drewes, H.W.; Lambooij, M.; Baan, C.A.; Meijboom, B.R.; Graafmans, W.C.; Westert, G.P.

    2011-01-01

    Background The oral anticoagulant therapy - provided to prevent thrombosis - is known to be associated with substantial avoidable hospitalization. Improving the quality of the oral anticoagulant therapy could avoid drug related hospitalizations. Therefore, this study compared the patient outcomes

  16. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  17. A comparative assessment of efficacy of three anticoagulant rodenticides.

    Science.gov (United States)

    Renapurkar, D M

    1982-01-01

    Results are presented of feeding tests carried out with three common anticoagulant rodenticides viz., coumatetralyl, fumarin and warfarin on three common species of commensal rodents i.e., Rattus rattus, Rattus norvegicus and Bandicota bengalensis. All three species of rodents were susceptible to anticoagulant rodenticides. However, the action of these compounds in B. bengalensis was comparatively slow. Coumatetralyl was found to be the most effective rodenticide followed by fumarin and warfarin. Liquid baits of these compounds are more effective in comparison to food baits.

  18. Inhibition of warfarin anticoagulation associated with chelation therapy.

    Science.gov (United States)

    Grebe, Heidi Braun; Gregory, Philip J

    2002-08-01

    Chelation therapy originally was administered exclusively to patients with heavy metal poisoning. Now some physicians are administering this therapy for numerous conditions, most commonly coronary heart disease. A 64-year-old man experienced impaired warfarin anticoagulation after undergoing chelation therapy His international normalized ratio (INR) fell from 2.6 the day before to 1.6 the day after therapy was administered. Whether chelation therapy decreases the effectiveness of warfarin anticoagulation is uncertain. However, because of this potential interaction, clinicians should consider increased INR monitoring in patients undergoing chelation therapy.

  19. Novel oral anticoagulants in the treatment of cerebral venous thrombosis

    DEFF Research Database (Denmark)

    Feher, G; Illes, Z; Komoly, S

    2015-01-01

    Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants...... (NOACs) have been extensively studied in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and non-valvular atrial fibrillation (NVAF). The aim of our work to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence...... to support the use of NOACs in CVT, although case series with rivaroxaban and dabigatran have showed promising results....

  20. Direct anticoagulants and nursing: an approach from patient's safety.

    Science.gov (United States)

    Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan

    In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. New oral anticoagulants in patients with chronic kidney disease.

    Science.gov (United States)

    Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema

    Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Regulatory, legislative, and policy updates with anticoagulant use.

    Science.gov (United States)

    Fanikos, John; Buckley, Leo F; Aldemerdash, Ahmed; Terry, Kimberly J; Piazza, Gregory; Connors, Jean M; Goldhaber, Samuel Z

    2015-04-01

    Thromboembolism afflicts millions of patients annually in the United States and is associated with a significant cost burden. Recent advances in oral anticoagulation have provided clinicians with more options for management of these diseases. Accordingly, regulatory, legislative, and policy-making organizations have intervened with the aim of improving patient outcomes, ensuring patient safety, and reducing costs. There have been a number of recent developments in surveillance, litigation, and regulatory oversight that clinicians should recognize. In this review article we summarize key updates related to the management of anticoagulant therapy as it relates to thrombosis prevention and treatment.

  3. Anticoagulant therapy duration. In favour of short-term courses.

    Science.gov (United States)

    Nieto Rodríguez, J A; Ramírez Luna, J C

    In recent years, we have observed a tendency to extend anticoagulant therapy for patients with venous thromboembolism disease (VTE). This practice exposes patients to a greater risk of severe and fatal haemorrhage, which, in certain conditions, outweighs the benefits related to the reduction in disease recurrence. This review examines the evidence in favour of reducing anticoagulant therapy as much as possible, especially for patients with VTE "caused" by temporary risk factors, with isolated deep vein thrombosis and with unprovoked VTE and a high risk of haemorrhage. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  4. Antiproliferative and quinone reductase-inducing activities of withanolides derivatives.

    Science.gov (United States)

    García, Manuela E; Nicotra, Viviana E; Oberti, Juan C; Ríos-Luci, Carla; León, Leticia G; Marler, Laura; Li, Guannan; Pezzuto, John M; van Breemen, Richard B; Padrón, José M; Hueso-Falcón, Idaira; Estévez-Braun, Ana

    2014-07-23

    Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structure-activity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4β,12β,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-26,23-olide (18) and (23R)-21-acetoxy-12β-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-26,23-lactame (20). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Cisplatin-induced Casepase-3 activation in different tumor cells

    Science.gov (United States)

    Shi, Hua; Li, Xiao; Su, Ting; Zhang, Yu-Hai

    2008-12-01

    Apoptosis plays an essential role in normal organism development which is one of the main types of programmed cell death to help tissues maintain homeostasis. Defective apoptosis can result in cell accumulation and therefore effects on tumor pathogenesis, progression and therapy resistance. A family of proteins, known as caspases, is typically activated in the early stages of apoptosis. Therefore, studying the kinetics of activation of caspases induced by antitumor drugs can contribute to antitumor drug discovery and explanation of the molecular mechanisms. This paper detected the Caspase-3 activity induced by cisplatin in human adenoid cystic carcinoma cell line (ACC-M), human hepatocellular liver carcinoma cell line (HepG2) and human epithelial carcinoma cell line (Hela) with stably expressing ECFP-DEVDDsRed (CD3) probe, a fluorescent probe consisting of Enhanced Cyan Fluorescent Protein (ECFP), red fluorescent protein (DsRed) and a linker with a recognition site of Caspase-3, by using the capillary electrophoresis (CE) and fluorescence resonance energy transfer (FRET) imaging system. Under the same concentration of cisplatin, ACC-M cells responded the most rapidly, and then HepG2 cells and Hela cells, respectively, in the early 30 hours. Later, HepG2 cells represented acceleration in the Caspase-3 activation speed and reached full activation the earliest comparing to other two cell types. The results demonstrated that ACC-M cell is more sensitive than the other two cell types under the treatment of cisplatin.

  6. Use of Thromboelastography (TEG) for Detection of New Oral Anticoagulants.

    Science.gov (United States)

    Dias, João D; Norem, Katherine; Doorneweerd, Derek D; Thurer, Robert L; Popovsky, Mark A; Omert, Laurel A

    2015-05-01

    The clinical introduction of new oral anticoagulants (NOACs) has stimulated the development of tests to quantify the effects of these drugs and manage complications associated with their use. Until recently, the only treatment choices for the prevention of venous thromboembolism in orthopedic surgical patients, as well as for stroke and systemic embolism in patients with atrial fibrillation, were vitamin K antagonists, antiplatelet drugs, and unfractionated and low-molecular-weight heparins. With the approval of NOACs, treatment options and consequent diagnostic challenges have expanded. To study the utility of thromboelastography (TEG) in monitoring and differentiating between 2 currently approved classes of NOACs, direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). Blood samples from healthy volunteers were spiked with each NOAC in both the presence and absence of ecarin, and the effects on TEG were evaluated. Both the kaolin test reaction time (R time) and the time to maximum rate of thrombus generation were prolonged versus control samples and demonstrated a dose response for apixaban (R time within the normal range) and dabigatran. The RapidTEG activated clotting time test allowed the creation of a dose-response curve for all 3 NOACs. In the presence of anti-Xa inhibitors, the ecarin test promoted significant shortening of kaolin R times to the hypercoagulable range, while in the presence of the direct thrombin inhibitor only small and dose-proportional R time shortening was observed. The RapidTEG activated clotting time test and the kaolin test appear to be capable of detecting and monitoring NOACs. The ecarin test may be used to differentiate between Xa inhibitors and direct thrombin inhibitors. Therefore, TEG may be a valuable tool to investigate hemostasis and the effectiveness of reversal strategies for patients receiving NOACs.

  7. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

  8. Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation.

    Science.gov (United States)

    Kloos, Bianca; Chakraborty, Sushmita; Lindner, Sonja G; Noack, Katrin; Harre, Ulrike; Schett, Georg; Krämer, Oliver H; Kubatzky, Katharina F

    2015-09-14

    Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis.

  9. NOX2-Induced Activation of Arginase and Diabetes-Induced Retinal Endothelial Cell Senescence

    Directory of Open Access Journals (Sweden)

    Modesto Rojas

    2017-06-01

    Full Text Available Increases in reactive oxygen species (ROS and decreases in nitric oxide (NO have been linked to vascular dysfunction during diabetic retinopathy (DR. Diabetes can reduce NO by increasing ROS and by increasing activity of arginase, which competes with nitric oxide synthase (NOS for their commons substrate l-arginine. Increased ROS and decreased NO can cause premature endothelial cell (EC senescence leading to defective vascular repair. We have previously demonstrated the involvement of NADPH oxidase 2 (NOX2-derived ROS, decreased NO and overactive arginase in DR. Here, we investigated their impact on diabetes-induced EC senescence. Studies using diabetic mice and retinal ECs treated with high glucose or H2O2 showed that increases in ROS formation, elevated arginase expression and activity, and decreased NO formation led to premature EC senescence. NOX2 blockade or arginase inhibition prevented these effects. EC senescence was also increased by inhibition of NOS activity and this was prevented by treatment with a NO donor. These results indicate that diabetes/high glucose-induced activation of arginase and decreases in NO bioavailability accelerate EC senescence. NOX2-generated ROS contribute importantly to this process. Blockade of NOX2 or arginase represents a strategy to prevent diabetes-induced premature EC senescence by preserving NO bioavailability.

  10. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs Versus Direct Oral Anticoagulants (DOACs

    Directory of Open Access Journals (Sweden)

    Rick H. van Gorp

    2015-11-01

    Full Text Available Vitamin K-antagonists (VKA are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs. As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

  11. QCM-D surpassing clinical standard for the dose administration of new oral anticoagulant in the patient of coagulation disorders.

    Science.gov (United States)

    Hussain, Munawar; Wendel, Hans Peter; Schmidt, Katrin; Langer, Elisabeth; Körber, Mareike Kristina; Faul, Oksana; Northoff, Hinnak; von Heymann, Christian; Gehring, Frank K

    2018-05-01

    The study focuses the dose administration of dabigatran to avoid the deaths due to hemorrhagic complications and thromboembolic stroke in clinics worldwide. To target the issue, a novel emerging acoustic technology, namely ''Quartz Crystal Microbalance with Dissipation'' (QCM-D) has been applied, while the acoustic assays namely ''activated Partial Thromboplastin Time'' (aPTT) and ''Prothrombinase complex-induced Clotting Test'' (PiCT) have been compared with the standard methods in parallel. Both techniques have been applied to 300 samples, including 220 plasma samples of patients suffering coagulation disorders and 80 plasma samples of non-patients. In comparison, the coagulation times of the acoustic aPTT and PiCT yielded an excellent correlation with the standard methods with in analytical standard deviation limits. Finally, the acoustic aPTT assay is the ''gold standard'' for a dose administration of the new oral anticoagulant, where the Δf/ΔΓ ratio of the acoustic assay demonstrates that dabigatran with FEIBA 50 combination could be a safe remedy to avoid the deaths in clinics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Bleeding in patients using new anticoagulants or antiplatelet agents: Risk factors and management

    NARCIS (Netherlands)

    Levi, M.M.; Eerenberg, E.; Löwenberg, E.; Kamphuisen, P.W.

    2010-01-01

    The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be

  13. [Economic consequences of biological monitoring and medical complications of injectable anticoagulants in France].

    Science.gov (United States)

    Paubel, P; Cousin, M; Amar, C; Gourmelen, J; Fabron, C; Detournay, B

    2016-12-01

    To assess the frequency of platelet monitoring and bleeding risks associated with the use of injectable anticoagulants in a real life setting and to estimate the associated costs. An analysis of the 2013 data from a random sample of ≈600,000 patients registered in the French National Health Insurances reimbursement database was conducted to identify platelet counts performed during injectable anticoagulants exposure period and treatment interruptions due to heparin-induced thrombocytopenia or transfusion. Events were then valued to establish associated costs. Overall 15,985 adult patients representing a cumulated injectable anticoagulants exposure time of 12,264 months were selected. Treatment sequences involved unfractionated heparin (2.8%), low molecular weight heparin (86.9%), and fondaparinux (13.1%). Patients treated with unfractionated heparin were older (77 vs. 57 and 59 years) with longer treatment duration (32.6 vs. 25.1 and 21 days). After statistical adjustment, the average monthly number of platelet counts was 1.36-fold lower in patients treated with fondaparinux compared to low molecular weight heparin (P<0.0001). No difference was found between low molecular weight heparin and fondaparinux regarding the incidence of bleeding with transfusion (P=0.76) or hospitalized thrombocytopenia (P=0.82). Extrapolated for the whole country, the estimated costs for biological monitoring were € 21.6 million for low molecular weight heparin and € 0.9 million for fondaparinux. Significantly fewer platelet counts were performed among patients treated with fondaparinux than among patients receiving low molecular weight heparin without additional bleeding risk. This finding should be taken into account when assessing the costs of such treatments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheters (TCC) thrombosis.

    Science.gov (United States)

    Colì, L; Donati, G; Cianciolo, G; Raimondi, C; Comai, G; Panicali, L; Nastasi, V; Cannarile, D C; Gozzetti, F; Piccari, M; Stefoni, S

    2006-01-01

    Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.

  15. Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

    Science.gov (United States)

    Krisper, Peter; Tiran, Beate; Fliser, Danilo; Haditsch, Bernd; Stadlbauer, Vanessa; Otto, Ronald; Ernst, Thomas; Kretschmer, Ulrich; Stauber, Rudolf E; Haller, Hermann; Holzer, Herwig; Manns, Michael P; Rifai, Kinan

    2010-01-01

    Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

  16. Monitoring strategies for patients treated with the new oral anticoagulants and the need for laboratory evaluation of hemostasis

    Directory of Open Access Journals (Sweden)

    Andrea Fontanella

    2013-12-01

    Full Text Available New oral anticoagulants that directly inhibit Factor IIa (dabigatran or Factor Xa (rivaroxaban, apixaban are currently available for prevention of venous thromboembolism (VTE after orthopedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over vitamin K antagonists including rapid onset, shorter half-lives, fewer drug interactions, and the lack of a need for routine monitoring. The fact that monitoring is not required should not, however, lead to lack of surveillance or a fire and forget medicine approach because there are several medical conditions that require careful clinical surveillance and, sometimes, laboratory monitoring. The main situations that require close monitoring are major bleeding, assessment of compliance (in particular during comorbidities other than vascular disease, e.g. dementia, overdose, sudden or progressive renal dysfunction, extreme body weight, concomitant use of other drugs that may induce impairment of new oral anticoagulants, need for urgent surgery.

  17. Fructokinase activity mediates dehydration-induced renal injury.

    Science.gov (United States)

    Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

    2014-08-01

    The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

  18. Prevention of thromboembolic events in patients with atrial fibrillation – new anticoagulants

    Directory of Open Access Journals (Sweden)

    Alexandre Holthausen Campos

    2011-09-01

    Full Text Available The authors present alternatives for the treatment of cardiacarrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as conveniencefor not requiring frequent laboratory controls.

  19. The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation

    Science.gov (United States)

    Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia

    2018-03-01

    Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

  20. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation...... in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load on the painful structures Udgivelsesdato: 2009/4...

  1. Anticoagulant rodenticide toxicity in six dogs presenting for ocular disease.

    Science.gov (United States)

    Griggs, Angela N; Allbaugh, Rachel A; Tofflemire, Kyle L; Ben-Shlomo, Gil; Whitley, David; Paulsen, Michael E

    2016-01-01

    To describe cases of suspected anticoagulant rodenticide toxicity manifesting with predominantly ocular signs. Six canine cases that presented to veterinary referral hospitals for ocular abnormalities and were diagnosed with suspected or confirmed anticoagulant rodenticide ingestion were reviewed for commonalities in presentation and outcome. Five dogs had unilateral ocular signs and one dog had bilateral manifestations. Signs included subconjunctival hemorrhage, exophthalmos, and commonly orbital pain without other significant physical examination findings. Prothrombin time was measured in 5 of 6 dogs and was prolonged in all. Partial thromboplastin time was measured in 4 of 6 dogs and was prolonged in all. Complete blood cell count and serum chemistry profiles demonstrated mild, if any, abnormalities. Five dogs had known anticoagulant rodenticide exposure, and rodenticide ingestion was suspected in 1 additional case based on clinical signs, clinical pathologic abnormalities, and response to treatment. Five of 6 cases were hospitalized overnight for plasma transfusions along with oral or injectable vitamin K1 , and all dogs were treated with oral vitamin K1 for 30 days. All dogs experienced complete resolution of clinical signs within 6 weeks of initiating treatment. Anticoagulant rodenticide toxicity can present with predominantly ocular manifestations. Rodenticide ingestion should be considered in dogs with unilateral or bilateral subconjunctival hemorrhage, exophthalmos, and orbital pain. © 2015 American College of Veterinary Ophthalmologists.

  2. Prevalence of Lupus Anticoagulant in Women with Spontaneous ...

    African Journals Online (AJOL)

    2017-10-26

    Oct 26, 2017 ... Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has been associated with SA in many ... (a hexagonal-phase phospholipid) test and calculated Rosner index for prolonged. KCT were used for the ... marker for APL syndrome, the demonstration that β2-GPI can bind to anionic ...

  3. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

    Directory of Open Access Journals (Sweden)

    Sara Nicole Fernández

    2014-01-01

    Full Text Available Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P=0.028. 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

  4. Haemorrhage in the labyrinth caused by anticoagulant therapy: case report

    Energy Technology Data Exchange (ETDEWEB)

    Callonnec, F.; Gerardin, E.; Thiebot, J. [Department of Radiology, Rouen University Hospital, 1 rue de Germont, F-76031 Rouen cedex (France); Marie, J.P.; Andrieu Guitrancourt, J. [Department of Otolaryngology, Rouen University Hospital (France); Marsot-Dupuch, K. [Department of Radiology, St. Antoine, Paris University Hospital (France)

    1999-06-01

    We report a patient who experienced a severe vertiginous episode with bilateral tinnitus and progressive right-sided hearing loss. She had Marfan`s disease and was on anticoagulant treatment. The fluid in the labyrinth gave higher signal than cerebrospinal fluid on T1-weighted images, suggesting haemorrhage. The radiological follow-up is discussed. (orig.) With 2 figs., 11 refs.

  5. Vitamin K and stability of oral anticoagulant therapy

    NARCIS (Netherlands)

    Rombouts, Eva Karolien

    2011-01-01

    One of the causes of unstable anticoagulation is a variable vitamin K intake. The main objective of this thesis was to test the hypothesis that the INR is particularly sensitive to changes in vitamin K intake when vitamin K status is low, and that patients with a low vitamin K intake would therefore

  6. Prevalence of Lupus Anticoagulant in Women with Spontaneous ...

    African Journals Online (AJOL)

    Introduction: Spontaneous abortion (SA) is a common complication of pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has been associated with SA in many studies, especially in Caucasians. This study was carried out to determine the prevalence of LA in women with SA in ABUTH, ...

  7. Challenges in management of Warfarin anti-coagulation in ...

    African Journals Online (AJOL)

    Challenges in management of Warfarin anti-coagulation in advanced HIV/AIDS patients with venous thrombotic events - A case series from a research clinic in rural Kericho, Kenya. ... VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least ...

  8. pattern of anticoagulation control after heart valve surgery at the ...

    African Journals Online (AJOL)

    hi-tech

    2000-07-07

    Jul 7, 2000 ... Regular attendance by the patients, supplemented by a system of quality control anticaogulation are the prerequisites of such a service. In some centres where such quality control systems are in place, levels of adequate. INR control maintained up to 80% of the patients attending the anticoagulation clinic ...

  9. Perioperative anticoagulation for children with prosthetic mechanical valves

    OpenAIRE

    Grech, Victor E.; Rees, Philip G.

    2000-01-01

    The insertion of a mechanical heart valve predisposes to thrombosis and embolism, and for this reason, individuals with mechanical valves who undergo dental/surgical procedures must take special precautions. In this article, we illustrate a protocol for anticoagulation during such procedures in individuals with mechanical valves.

  10. Standardisation of the Laboratory Control of Anticoagulant Therapy

    African Journals Online (AJOL)

    1974-09-11

    Sep 11, 1974 ... Anticoagulant therapy with the coumarin group of drugs has been used in clinical practice for more than a quarter of a century. The most widely used form of laboratory control of the treatment is the Quick one-stage prothrom·- bin time. I. This simple test proved to be satisfactory in most cases, but discrepant ...

  11. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants

    NARCIS (Netherlands)

    Broekema, Ferdinand I.; van Minnen, Baucke; Jansma, Johan; Bos, Rudolf R. M.

    To avoid increasing the risk of thromboembolic events, it is recommended that treatment with anticoagulants should be continued during dentoalveolar operations. We have evaluated the incidence of bleeding after dentoalveolar operations in a prospective study of 206 patients, 103 who were, and 103

  12. Sequential activation of proteases in radiation induced apoptosis

    International Nuclear Information System (INIS)

    Watters, D.; Waterhouse, N.

    1997-01-01

    Full text: Significant advances have been made in recent years in unraveling the molecular mechanisms of apoptosis particularly in relation to Fas- and TNF-mediated cell death, however there are considerable gaps in our knowledge of the processes involved in apoptosis induced by ionizing radiation. We have used the degradation of specific proteolytic targets in a pair of isogenic Burkitt's Iymphoma cells lines (BL30A, sensitive and BL30K resistant) to study the sequence of events in the execution of radiation-induced apoptosis. Fodrin can be cleaved to fragments of 150 kDa and 120 kDa. In the case of Fas-mediated apoptosis both cleavages are inhibited by the caspase inhibitor zVAD-fmk at 10 μM, a concentration which inhibits all the hallmarks of apoptosis. However in radiation-induced apoptosis, inhibition of the clevage of fodrin to the 150 kDa fragment requires 100 μM zVAD-fink while apoptosis itself is inhibited at 10 μM. This suggests that different enzymes are responsible for the generation of the 150 kDa fragment in the two models of apoptosis. Fodrin has been reported to be cleaved by μ-calpain to a 150 kDa fragment however, the involvement of μ-calpain in apoptosis has not yet been established. In murine fodrin there is a caspase cleavage site within 1 kDa of the calpain cleavage site. In vitro studies using purified enzymes showed that only caspase-3 and μ-calpain could cleave fodrin in untreated cell extracts to the same sized fragments as seen during apoptosis in vivo. We provide evidence for the early activation of μ-calpain after ionizing radiation in the sensitive BL30A cell line, and show that the time course of μ-calpain activation parallels that of the appearance of the 150 kDa fragment. Caspase-3 is activated much later and is likely to be responsible for the generation of the 120 kDa fragment. μ-Calpain was not activated in the resistant cell line. Based on these results we propose a model for the proteolytic cascade in radiation-induced

  13. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Hino, Atsuko; Ohta, Shigeru

    2008-01-01

    AMP-activated protein kinase (AMPK), a member of the metabolite-sensing protein kinase family, is activated by energy deficiency and is abundantly expressed in neurons. The environmental pollutant, tributyltin chloride (TBT), is a neurotoxin, and has been reported to decrease cellular ATP in some types of cells. Therefore, we investigated whether TBT activates AMPK, and whether its activation contributes to neuronal cell death, using primary cultures of cortical neurons. Cellular ATP levels were decreased 0.5 h after exposure to 500 nM TBT, and the reduction was time-dependent. It was confirmed that most neurons in our culture system express AMPK, and that TBT induced phosphorylation of AMPK. Compound C, an AMPK inhibitor, reduced the neurotoxicity of TBT, suggesting that AMPK is involved in TBT-induced cell death. Next, the downstream target of AMPK activation was investigated. Nitric oxide synthase, p38 phosphorylation and Akt dephosphorylation were not downstream of TBT-induced AMPK activation because these factors were not affected by compound C, but glutamate release was suggested to be controlled by AMPK. Our results suggest that activation of AMPK by TBT causes neuronal death through mediating glutamate release

  14. Trypsin-induced ATPase activity in potato mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Jung, D.W.; Laties, G.G.

    1976-04-01

    Potato mitochondria (Solanum tuberosum var. Russet Burbank), which readily phosphorylate ADP in oxidative phosphorylation, show low levels of ATPase activity which is stimulated neither by Mg/sup 2 +/, 2,4-dinitrophenol, incubation with respiratory substrates, nor disruption by sonication or treatment with Triton X-100, individually or in concert. Treatment of disrupted potato mitochondria with trypsin stimulates Mg/sup 2 +/-dependent, oligomycin-sensitive ATPase activity 10- to 15-fold, suggesting the presence of an ATPase inhibitor protein. Trypsin-induced ATPase activity was unaffected by uncoupler. Oligomycin-sensitive ATPase activity decreases as exposure to trypsin is increased. Incubation at alkaline pH or heating at 60/sup 0/C for 2 minutes also activates ATPase of sonicated potato mitochondria. Disruption of cauliflower (Brassica oleracea), red sweet potato (Ipomoea batatas), and carrot (Daucus carota) mitochondria increases ATPase activity, which is further enhanced by treatment with trypsin. The significance of the tight association of the inhibitor protein and ATPase in potato mitochondria is not clear.

  15. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  16. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, BlockEx VivoEquid Herpesvirus Type-1-Induced Platelet Activation.

    Science.gov (United States)

    Stokol, Tracy; Serpa, Priscila Beatriz da Silva; Zahid, Muhammad N; Brooks, Marjory B

    2016-01-01

    Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins) or platelet inhibitors that impede post-receptor thrombin signaling [phosphodiesterase (PDE) antagonists] would inhibit EHV-1-induced platelet activation ex vivo . We exposed platelet-rich plasma (PRP) collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque-forming unit/cell in the presence or absence of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX), and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1-0.2 U/mL anti-factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM, but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX) or isoenzyme-3 selective (cilostazol) PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  17. Unfractionated and low-molecular-weight heparin and the phosphodiesterase inhibitors, IBMX and cilostazol, block ex vivo Equid Herpesvirus type-1-induced platelet activation

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    2016-11-01

    Full Text Available Equid herpes virus type-1 (EHV-1 is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins or platelet inhibitors that impede post-receptor thrombin signaling (phosphodiesterase [PDE] antagonists would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque forming unit/cell in the presence or absence of unfractionated heparin (UFH, low-molecular-weight (LMWH heparin or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1 to 0.2 U/mL anti-Factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX or isoenzyme-3 selective (cilostazol PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  18. Hypoxia induced cognitive impairment modulating activity of Cyperus rotundus.

    Science.gov (United States)

    Kandikattu, Hemanth Kumar; Deep, Satya Narayan; Razack, Sakina; Amruta, Narayanappa; Prasad, Dipti; Khanum, Farhath

    2017-06-01

    Hypobaric hypoxia leads to decrease in cellular oxygen content which subsequently damages the hippocampus with an increase in brain oxidative stress and impairs the memory of the individual. In the present study, we have evaluated the cognitive impairment modulating activity of total oligomeric flavonoids fraction of Cyperus rotundus (TOF) in Sprague Dawley rats. The rats were trained for memory activity for a period of 7days followed by 7days exposure to 25,000ft. altitude and the spatial reference memory was evaluated. Behavioral analysis of the rats by Morris water maze experiment showed that TOF supplementation enhanced the spatial reference memory activity of the rats exposed to hypobaric hypoxia. The decrease in antioxidant status of the animals exposed to hypoxia was restored with TOF supplementation. The increase in ROS, lipid peroxidation products and protein carbonyls of the hippocampus was significantly decreased in animals with TOF administration. The histological assessment of the pyramidal cells of the hippocampus of hypoxia-exposed animals showed nuclear damage and TOF supplementation prevented nuclear damage. TOF administration suppressed hypoxia-induced increase in serotonin, dopamine, and norepinephrine. GABA and Ach levels were decreased by hypoxia which was prevented by TOF supplementation. The increase in GFAP, HIF-1α and VEGF expression in CA3 region of the hippocampus in hypoxia-exposed rats was decreased in TOF administered rats. Taken together, TOF extract ameliorates hypobaric hypoxia induced memory impairment and neurodegeneration in hippocampus through its anti-stress effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Hypocapnia induces caspase-3 activation and increases Abeta production.

    Science.gov (United States)

    Xie, Zhongcong; Moir, Robert D; Romano, Donna M; Tesco, Giuseppina; Kovacs, Dora M; Tanzi, Rudolph E

    2004-01-01

    At least half of all cases of early onset (<60) familial Alzheimer's disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death. We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta-protein (Abeta) production, and assessed the influence of the PS1Delta9 FAD mutation on these effects. For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO2<40 mm Hg) and hypocapnia plus hypoxia (PO2<21%). Hypocapnia (20 mm Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1Delta9 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO2) and hypoxia (5%O2) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased Abeta production. The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis. Copyright (c) 2004 S. Karger AG, Basel.

  20. Primary care monitoring of patients under oral anticoagulation.

    Science.gov (United States)

    Agnelo, Pedro; Alexandra, Denise; Matias, Sara

    2014-01-01

    With the advent of new oral anticoagulants that do not require regular laboratory control but are significantly more expensive, there has been renewed interest in the quality of the classic agents and the monitoring of patients taking them. We set out to analyze time in therapeutic range of patients under oral anticoagulation monitored in our health unit, to determine whether primary care monitoring is comparable to that in anticoagulation clinics. At the same time, we aimed to ascertain whether there was any association between the dosing method (unit protocol vs. computer-assisted) and the time in therapeutic range achieved.Methods We analyzed all INR values determined in our health unit during the first six months of 2012, using Excel 2007 and SPSS version 17.0, and applying the Student's t test for a level of significance of 0.05. All INR assessments during the first six months of 2012 were recorded, a total of 320 tests; mean patient age was 69.9±11.25 years, 63% male. Dose adjustments were made according to the unit protocol in 77% of cases. Atrial fibrillation was the most prevalent indication. Most values (65.3%) were within the target therapeutic range; 24.1% were subtherapeutic and 10.6% supratherapeutic. Computer-assisted dosing achieved better control than the protocol (72.5% vs. 62.9%), without statistical significance. Primary care monitoring of oral anticoagulation appears to be comparable to that in anticoagulation clinics, while affording better access and cost reductions. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  1. Adverse effects of anticoagulation treatment: clinically significant upper gastrointestinal hemorrhage

    Directory of Open Access Journals (Sweden)

    Pavel Skok

    2006-12-01

    Full Text Available Background: Over the last years, the use of oral anticoagulant treatment has increased dramatically, principally for the prevention of venous thrombosis and thrombembolic events. This treatment is demanding, especially among the elderly with concommitant diseases and different medication. Aim of the study to evaluate the rate of serious complications, clinically significant hemorrhage from upper gastointestinal tract in patients treated with oral antiocoagulants in a prospective cohort study.Patients and methods: Included were patients admitted to our institution between January 1, 1994 and December 31, 2003 due to gastrointestinal hemorrhage. Emergency endoscopy and laboratory testing was performed in all patients.Results: 6416 patients were investigated: 2452 women (38.2 % and 3964 men (61.8 %, mean age 59.1 years, SD 17.2. Among our patients, 55 % were aged over 60 years. In 86.4 % of patients the source of bleeding was confirmed in the upper gastrointestinal tract. In the last week prior to bleeding, 20.4 % (1309/6416 of all patients were regularly taking nonsteroidal anti-inflammatory drugs, anticoagulant therapy or antiplatelet agents in single daily doses at least. 6.3 % of patients (82/1309 with abundant hemorrhage from upper gastrointestinal tract were using oral anticoagulant therapy and had INR > 5 at admission, 25.6 % of them had INR > 10. The mortality of patients using oral anticoagulants and INR > 5 was 17.1 %.Conclusions: Upper gastrointestinal hemorrhage is a serious complication of different medications, particularly in elderly patients. Safe use of anticoagulant therapy is based on careful selection of patients and correct intake of the prescribed drugs.

  2. Transition polarizability model of induced resonance Raman optical activity

    Czech Academy of Sciences Publication Activity Database

    Yamamoto, S.; Bouř, Petr

    2013-01-01

    Roč. 34, č. 25 (2013), s. 2152-2158 ISSN 0192-8651 R&D Projects: GA ČR GAP208/11/0105; GA ČR GA13-03978S; GA MŠk(CZ) LH11033 Grant - others:AV ČR(CZ) M200551205 Institutional support: RVO:61388963 Keywords : induced resonance Raman optical activity * europium complexes * density functional computations * light scattering Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.601, year: 2013

  3. Hypoxia activated EGFR signaling induces epithelial to mesenchymal transition (EMT.

    Directory of Open Access Journals (Sweden)

    Ashish Misra

    Full Text Available Metastasis is a multi-step process which requires the conversion of polarized epithelial cells to mesenchymal cells, Epithelial-Mesenchymal Transition (EMT. EMT is essential during embryonic morphogenesis and has been implicated in the progression of primary tumors towards metastasis. Hypoxia is known to induce EMT; however the molecular mechanism is still poorly understood. Using the A431 epithelial cancer cell line, we show that cells grown under hypoxic conditions migrated faster than cells grown under normal oxygen environment. Cells grown under hypoxia showed reduced adhesion to the extracellular matrix (ECM probably due to reduced number of Vinculin patches. Growth under hypoxic conditions also led to down regulation of E-cadherin and up regulation of vimentin expression. The increased motility of cells grown under hypoxia could be due to redistribution of Rac1 to the plasma membrane as opposed to increased expression of Rac1. EGF (Epidermal Growth Factor is a known inducer of EMT and growth of A431 cells in the absence of oxygen led to increased expression of EGFR (EGF Receptor. Treatment of A431 cells with EGF led to reduced cell adhesion to ECM, increased cell motility and other EMT characteristics. Furthermore, this transition was blocked by the monoclonal antibody Cetuximab. Cetuximab also blocked the hypoxia-induced EMT suggesting that cell growth under hypoxic conditions led to activation of EGFR signaling and induction of EMT phenotype.

  4. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    Science.gov (United States)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  5. Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

    Science.gov (United States)

    Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

    2017-05-01

    Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Influence of the sample anticoagulant on the measurements of impedance aggregometry in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Cristina Solomon

    2008-10-01

    Full Text Available Cristina Solomon1, Michael Winterhalter1, Isabel Gilde1, Ludwig Hoy2, Andreas Calatzis3, Niels Rahe-Meyer11Department of Anesthesiology, Hannover Medical School, Hannover, Germany; 2Institute for Biometry, Hannover Medical School, Hannover, Germany; 3Department Hemostasis Transfusion Medicine, University Hospital Munich, Munich, GermanyBackground: The standard method of assessment of platelet function is represented by light transmission aggregometry (LTA, performed in citrated platelet-rich plasma (PRP. With LTA, decrease and subsequent post-cardiopulmonary bypass (CPB recovery of platelet function have been reported during cardiac surgery. Multiple electrode aggregometry (MEA may be used as point-of-care method to monitor perioperative changes in platelet function. Since MEA assesses macroaggregation which is influenced by the plasmatic levels of unbound calcium, citrate may be inadequate as anticoagulant for MEA. We used citrate and heparin for MEA samples, to see with which anticoagulant the intraoperative decrease and postoperative recovery in platelet function previously described with other aggregometric methods in cardiac surgery may be observed with MEA.Methods: Blood was obtained from 60 patients undergoing routine cardiac surgery and the samples were collected in standard tubes containing unfractionated heparin (50 U/mL or trisodium citrate (3.2%. The samples were obtained before CPB, at 30 minutes on CPB, end of CPB and on the first postoperative day. MEA was performed using the Multiplate® analyzer. Collagen (COLtest, 100 μg/mL and TRAP-6 (thrombin receptor activating peptide, TRAPtest, 1mM/mL were used as aggregation agonists.Results: Platelet aggregometric response decreased significantly during CPB. Platelet aggregation assessed using TRAP-6 as agonist on heparinized blood significantly correlated with the duration of CPB (r = −0.41, p = 0.001, 2-tailed Pearson test. The aggregometric analysis performed on the first

  7. Active Control Does Not Eliminate Motion-Induced Illusory Displacement

    Directory of Open Access Journals (Sweden)

    Ian M. Thornton

    2011-05-01

    Full Text Available When the sine-wave grating of a Gabor patch drifts to the left or right, the perceived position of the entire object is shifted in the direction of local motion. In the current work we explored whether active control of the physical position of the patch overcomes such motion induced illusory displacement. In Experiment 1 we created a simple computer game and asked participants to continuously guide a Gabor patch along a randomly curving path using a joystick. When the grating inside the Gabor patch was stationary, participants could perform this task without error. When the grating drifted to either left or right, we observed systematic errors consistent with previous reports of motion-induced illusory displacement. In Experiment 2 we created an iPad application where the built-in accelerometer tilt control was used to steer the patch through as series of “gates”. Again, we observed systematic guidance errors that depended on the direction and speed of local motion. In conclusion, we found no evidence that participants could adapt or compensate for illusory displacement given active control of the target.

  8. Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang

    2009-01-01

    Full Text Available Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β. Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 μM concentration-dependently inhibited lipopolysaccharide (LPS-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM. Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2 phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

  9. FOXO1 mediates RANKL-induced osteoclast formation and activity.

    Science.gov (United States)

    Wang, Yu; Dong, Guangyu; Jeon, Hyeran Helen; Elazizi, Mohamad; La, Lan B; Hameedaldeen, Alhassan; Xiao, E; Tian, Chen; Alsadun, Sarah; Choi, Yongwon; Graves, Dana T

    2015-03-15

    We have previously shown that the transcription factor FOXO1 is elevated in conditions with high levels of bone resorption. To investigate the role of FOXO1 in the formation of osteoclasts, we examined mice with lineage-specific deletion of FOXO1 in osteoclast precursors and by knockdown of FOXO1 with small interfering RNA. The receptor activator for NF-κB ligand (RANKL), a principal bone-resorbing factor, induced FOXO1 expression and nuclear localization 2 d after stimulation in bone marrow macrophages and RAW264.7 osteoclast precursors. RANKL-induced osteoclast formation and osteoclast activity was reduced in half in vivo and in vitro with lineage-specific FOXO1 deletion (LyzM.Cre(+)FOXO1(L/L)) compared with matched controls (LyzM.Cre(-)FOXO1(L/L)). Similar results were obtained by knockdown of FOXO1 in RAW264.7 cells. Moreover, FOXO1-mediated osteoclast formation was linked to regulation of NFATc1 nuclear localization and expression as well as a number of downstream factors, including dendritic cell-specific transmembrane protein, ATP6vod2, cathepsin K, and integrin αv. Lastly, FOXO1 deletion reduced M-CSF-induced RANK expression and migration of osteoclast precursors. In the present study, we provide evidence that FOXO1 plays a direct role in osteoclast formation by mediating the effect of RANKL on NFATc1 and several downstream effectors. This is likely to be significant because FOXO1 and RANKL are elevated in osteolytic conditions. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Chang-Jiang, E-mail: panchangjiang@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China); Pang, Li-Qun [Department of General Surgery, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an 223300 (China); Gao, Fei [Zhejiang Zylox Medical Devices Co., Ltd., Hangzhou 310000 (China); Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China)

    2016-06-01

    Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents. - Highlights: • Heparin-loaded graphene oxide coating was

  11. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

    Directory of Open Access Journals (Sweden)

    Mark R. Hutchinson

    2007-01-01

    Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

  12. Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals

    Science.gov (United States)

    Odaka, C; Mizuochi, T

    2000-01-01

    Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) which is widely used as an anti-hypertensive agent. In addition to its ability to reduce blood pressure, captopril has a number of other biological activities. Recently the drug was shown to inhibit Fas-induced apoptosis in human activated peripheral T cells and human lung epithelial cells. In this study, we investigated whether captopril blocks activation-induced apoptosis in murine T cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic cell death upon activation with anti-CD3 antibody. In addition, captopril inhibited an inducible caspase-3-like activity during activation-induced apoptosis. On the other hand, captopril did not interfere with Fas signalling, since anti-Fas antibody-induced apoptosis in Fas+ Jurkat cells was unaffected by the drug. Furthermore, we examined whether captopril blocks activation-induced apoptosis by interfering with expression of Fas, Fas ligand (FasL), or both on T cell hybridomas. FasL expression on activated T cells was significantly inhibited by captopril, whereas up-expression of Fas was partially inhibited, as assessed by cell surface staining. Taking all data together, we conclude that captopril prevents activation-induced apoptosis in T cell hybridomas by interfering with T cell activation signals. Captopril has been reported to induce systemic lupus erythematosus syndrome, and our findings may be useful for elucidating the mechanism of captopril-induced autoimmunity. PMID:10971519

  13. Antiplatelet and anticoagulation for patients with prosthetic heart valves.

    Science.gov (United States)

    Massel, David R; Little, Stephen H

    2013-07-09

    Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimise this risk. An important issue is the effectiveness and safety of the latter strategy. This is an update of our previous review; the goal was to create a valid synthesis of all available, methodologically sound data to further assess the safety and efficacy of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulant monotherapy in patients with prosthetic heart valves. We updated the previous searches from 2003 and 2010 on 16 January 2013 and searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 12), MEDLINE (OVID, 1946 to January Week 1 2013), and EMBASE (OVID, 1980 to 2013 Week 02). We have also looked at reference lists of individual reports, review articles, meta-analyses, and consensus statements. We included reports published in any language or in abstract form. All reports of randomised controlled trials comparing standard-dose oral anticoagulation to standard-dose oral anticoagulation and antiplatelet therapy in patients with one or more prosthetic heart valves. Two review authors independently performed the search strategy, assessed trials for inclusion and study quality, and extracted data. We collected adverse effects information from the trials. One new study has been identified and included in this update. In total, 13 studies involving 4122 participants were included in this review update. Years of publication ranged from 1971 to 2011. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with

  14. Anticoagulant, antiplatelet and antianemic effects of Punica granatum (pomegranate) juice in rabbits.

    Science.gov (United States)

    Riaz, Azra; Khan, Rafeeq A

    2016-04-01

    Pomegranate (Punica granatum L., Punicaceae) is a good source of minerals and phytochemicals with diverse pharmacological activities such as anxiolytic, antidepressant, hypoglycemic, hypolipidemic, and anti-inflammatory activities. Effects of P. granatum on blood parameters and coagulation have, however, been little studied. The aim of the study was to assess the outcome of P. granatum on coagulation and anticoagulation factors at different doses on blood samples of healthy white rabbits. Blood samples of the animals were collected twice during the study and biochemical assays were performed to assess the effect on hematological, coagulation, anticoagulation, and platelet aggregation. Significant changes were observed in erythrocytes, hemoglobin, and mean corpuscular hemoglobin concentration, while bleeding and thrombin time were also prolonged significantly. There was significant increase in protein C, thrombin antithrombin complex levels, and decrease in platelet aggregation and fibrinogen concentration, in a dose-dependent manner. The results of hematological and coagulation assays lead to the speculation about a possible antianemic and cardioprotective effect of P. granatum.

  15. Formation of Tankyrase Inhibitor-Induced Degradasomes Requires Proteasome Activity.

    Directory of Open Access Journals (Sweden)

    Nina Marie Pedersen

    Full Text Available In canonical Wnt signaling, the protein levels of the key signaling mediator β-catenin are under tight regulation by the multimeric destruction complex that mediates proteasomal degradation of β-catenin. In colorectal cancer, destruction complex activity is often compromised due to mutations in the multifunctional scaffolding protein Adenomatous Polyposis Coli (APC, leading to a stabilization of β-catenin. Recently, tankyrase inhibitors (TNKSi, a novel class of small molecule inhibitors, were shown to re-establish a functional destruction complex in APC-mutant cancer cell lines by stabilizing AXIN1/2, whose protein levels are usually kept low via poly(ADP-ribosylation by the tankyrase enzymes (TNKS1/2. Surprisingly, we found that for the formation of the morphological correlates of destruction complexes, called degradasomes, functional proteasomes are required. In addition we found that AXIN2 is strongly upregulated after 6 h of TNKS inhibition. The proteasome inhibitor MG132 counteracted TNKSi-induced degradasome formation and AXIN2 stabilization, and this was accompanied by reduced transcription of AXIN2. Mechanistically we could implicate the transcription factor FoxM1 in this process, which was recently shown to be a transcriptional activator of AXIN2. We observed a substantial reduction in TNKSi-induced stabilization of AXIN2 after siRNA-mediated depletion of FoxM1 and found that proteasome inhibition reduced the active (phosphorylated fraction of FoxM1. This can explain the decreased protein levels of AXIN2 after MG132 treatment. Our findings have implications for the design of in vitro studies on the destruction complex and for clinical applications of TNKSi.

  16. Attenuation of cocaine-induced locomotor activity in male and female mice by active immunization.

    Science.gov (United States)

    Kosten, Therese A; Shen, Xiaoyun Y; Kinsey, Berma M; Kosten, Thomas R; Orson, Frank M

    2014-01-01

    Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Male and female BALB/c mice were vaccinated (n = 44) or served as non-vaccinated controls (n = 34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7 weeks and plasma obtained at 8 weeks to assess antibody levels. High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. © American Academy of Addiction Psychiatry.

  17. Oral anticoagulants for stroke prevention in atrial fibrillation.

    Science.gov (United States)

    Senoo, Keitaro; Lane, Deirdre A; Lip, Gregory Y H

    2014-09-01

    The availability of 4 non-vitamin K oral anticoagulants (NOACs), that is, dabigatran, rivaroxaban, apixaban, and edoxaban, has changed the landscape of stroke prevention in patients with atrial fibrillation. This review article provides an overview of the 4 phase III studies that have compared these NOACs, examining major outcomes of efficacy and safety. A range of practical questions relating to the NOACs have emerged, including topics such as patient selection, treating patients with renal impairment, treating elderly patients, and combining anticoagulant therapy with antiplatelet drugs. We also address the interaction of various patient characteristics with the treatments and suggest the features can assist the physician in the choice of a particular NOAC for a particular patient(s). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Recent developments in the use of oral anticoagulants

    DEFF Research Database (Denmark)

    Lassen, Michael R

    2009-01-01

    For many years, vitamin K antagonists, unfractionated heparins, low-molecular-weight heparins and a pentasaccharide were the only anticoagulant drugs available for the prevention of venous thromboembolism after surgery. However, their benefits were associated with disadvantages, such as their sub......For many years, vitamin K antagonists, unfractionated heparins, low-molecular-weight heparins and a pentasaccharide were the only anticoagulant drugs available for the prevention of venous thromboembolism after surgery. However, their benefits were associated with disadvantages......, such as their subcutaneous route of administration or the need for coagulation monitoring. Research was challenged to develop new drugs that would simplify thromboprophylaxis while showing equivalent or better efficacy. Rivaroxaban and dabigatran are now available in some countries for the prevention of venous...

  19. Self-management of oral anticoagulant therapy in two centers

    DEFF Research Database (Denmark)

    Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard

    Self-management of oral anticoagulant therapy in two centers: 11.000 patient-years of follow-up H Nilsson1,2,3, EL Grove2, TB Larsen3, M Maegaard1, TD Christensen1 1Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Aarhus; 2Department...... of Cardiology, Aarhus University Hospital, Aarhus; 3Department of Cardiology, Aalborg Hospital & Department of Health Science and Technology, Aalborg University, Aalborg, Denmark haana_86@hotmail.com Objectives: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists have...... clinical practice. Materials and methods: A case-series study including all patients who had passed an exam in PSM in the period 1995-2012 at Aarhus University Hospital or Aalborg University Hospital, including 2200 patients and 11000 patient-years in total. The effectiveness was measured using...

  20. Active Emergence from Propofol General Anesthesia is Induced by Methylphenidate

    Science.gov (United States)

    Chemali, Jessica J.; Van Dort, Christa J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. METHODS Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of methylphenidate to restore righting during a continuous target controlled infusion of propofol was also tested. In a separate group of rats, a target controlled infusion of propofol was established and spectral analysis was performed on electroencephalogram recordings taken before and after methylphenidate administration. RESULTS Methylphenidate decreased median time to emergence after a single dose of propofol from 735 seconds (95% CI: 598 to 897 seconds, n=6) to 448 seconds (95% CI: 371 to 495 seconds, n=6). The difference was statistically significant (p = 0.0051). During continuous propofol anesthesia with a median final target plasma concentration of 4.0 μg/ml (95%CI: 3.2 to 4.6, n=6), none of the rats exhibited purposeful movements after injection of normal saline. After methylphenidate, however, all 6 rats promptly exhibited arousal and had restoration of righting with a median time of 82 seconds (95% CI: 30 to 166 seconds). Spectral analysis of electroencephalogram data demonstrated a shift in peak power from delta (anesthesia in rats. Further study is warranted to test the hypothesis that methylphenidate induces emergence from propofol general anesthesia in humans. PMID:22446983

  1. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  2. TENS attenuates repetition-induced summation of activity-related pain following experimentally induced muscle soreness.

    Science.gov (United States)

    Mankovsky-Arnold, Tsipora; Wideman, Timothy H; Larivière, Christian; Sullivan, Michael J L

    2013-11-01

    This study sought to determine whether repetition-induced summation of activity-related pain (RISP) could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain. This study also assessed the effects of transcutaneous electrical nerve stimulation on RISP. The relation between the index of RISP and psychological factors such as catastrophizing and fear of pain was also explored. The sample consisted of 56 healthy (35 women, 21 men) participants who underwent 2 testing sessions, separated by 24 hours. In the first session, musculoskeletal pain was induced with a delayed-onset muscle soreness protocol. During the second session, participants were randomly assigned to the transcutaneous electrical nerve stimulation or placebo condition and were asked to rate their pain as they lifted a series of 18 weighted canisters. An index of RISP was derived as the change in pain ratings across repeated lifts. Approximately 25% of participants showed evidence of RISP. Results also revealed that transcutaneous electrical nerve stimulation attenuated the RISP effect. Psychological measures (fear of pain, catastrophizing) were not significantly correlated with the index of RISP, but the index of RISP was significantly correlated with a measure of physical tolerance. Discussion addresses the clinical implications of the findings as well as the potential mechanisms underlying RISP. This study showed that RISP could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain with delayed-onset muscle soreness. Transcutaneous electrical nerve stimulation led to a significant reduction in RISP. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Net clinical benefit of combination anticoagulant and antiplatelet therapy versus anticoagulation alone in atrial fibrillation patients: Results from the amadeus trial

    NARCIS (Netherlands)

    Lane, Deirdre; Kamphuisen, Pieter; Minini, Pascal; De Peuter, Olaf R.; Buller, Harry R.; Lip, Gregory Y. H.

    2010-01-01

    Background: To compare the effect of combination anticoagulant and antiplatelet (AP) therapy with anticoagulation alone on stroke and bleeding risk in atrial fibrillation (AF) patients and examine predictors of clinically relevant bleeding. Methods: Post-hoc analysis of 4576 AF patients [mean (SD)

  4. Platelet-activating factor-induced increases in glucose kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Lang, C.H.; Dobrescu, C.; Hargrove, D.M.; Bagby, G.J.; Spitzer, J.J. (Louisiana State Univ. Medical Center, New Orleans (USA))

    1988-02-01

    Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose before and for 4 h after either a bolus injection or a constant infusion of PAF. The bolus injection of PAF elevated the rate of glucose appearance (R{sub a}; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose and glucose R{sub a} throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. Because the constant infusion of PAF did stimulate many of the hemodynamic and metabolic alterations produced by endotoxin, this study provides additional support for the potential importance of PAF as a mediator of the early hemodynamic and metabolic sequela of endotoxin shock. Furthermore, the PAF-induced changes in glucose metabolism appear to be mediated by the resultant elevation in plasma catecholamines.

  5. Mechanism of Hydrophilicity by Radiation-Induced Surface Activation

    Science.gov (United States)

    Honjo, Yoshio; Furuya, Masahiro; Takamasa, Tomoji; Okamoto, Koji

    When a metal oxide is irradiated by gamma rays, the irradiated surface becomes hydrophilic. This surface phenomenon is called as radiation-induced surface activation (RISA) hydrophilicity. In order to investigate gamma ray-induced and photoinduced hydrophilicity, the contact angles of water droplets on a titanium dioxide surface were measured in terms of irradiation intensity and time for gamma rays of cobalt-60 and for ultraviolet rays. Reciprocals of the contact angles increased in proportion to the irradiation time before the contact angles reached its super-hydrophilic state. The irradiation time dependency is equal to each other qualitatively. In addition, an effect of ambient gas was investigated. In pure argon gas, the contact angle remains the same against the irradiation time. This clearly indicates that certain humidity is required in ambient gas to take place of RISA hydrophilicity. A single crystal titanium dioxide (100) surface was analyzed by X-ray photoelectron spectrometry (XPS). After irradiation with gamma rays, a peak was found in the O1s spectrum, which indicates the adsorption of dissociative water to a surface 5-fold coordinate titanium site, and the formation of a surface hydroxyl group. We conclude that the RISA hydrophilicity is caused by chemisorption of the hydroxyl group on the surface.

  6. Unveiling Unexpected Immune Activities Induced by Your Pneumococcal Vaccine

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2016-03-01

    Full Text Available In modern-day vaccine design, a good pneumococcal capsular polysaccharide vaccine is measured by its ability to induce opsonic antibodies. These antibodies label bacteria for phagocytosis by neutrophils and thereby overcome the capsule’s barrier function. Doyle and Pirofski have raised a serious challenge to the current paradigm by describing anti-capsular antibodies that are highly protective but nonopsonic [C.R. Doyle and L. Pirofski, mBio 7(1:e02260-15, 2016, doi:10.1128/mBio.02260-15]. In fact, some functions are not related to neutrophils or phagocytosis at all. An increased awareness of these activities is critical not only for accurate comparisons of vaccine candidates but also for improvements in vaccination outcomes in settings of neutropenia. When vaccine developers select a single gatekeeper assay (e.g., an opsonophagocytic assay for bacteria or a neutralization assay for viruses, promising vaccine candidates may be missed. Doyle and Pirofski stress that multiple functions, not just one, should be investigated to enhance discovery of antibody mechanisms and to best assess vaccine-induced correlates of immune protection.

  7. [Clinical perspectives on the management of bleeding in patients on oral anticoagulants: the DECOVER Study (DElphi Consensus on oral COagulation and therapy action reVERsal)].

    Science.gov (United States)

    Vicente, Vicente; Martín, Alfonso; Lecumberri, Ramón; Coll-Vinent, Blanca; Suero, Coral; González-Porras, José Ramón; Marco, Pascual; Mateo, José; Roldán, Vanesa; Soulard, Stéphane; Crespo, Carlos; Camats, Míriam

    2017-02-01

    To evaluate the level of agreement between hematologists and emergency medicine physicians regarding the best clinical practices for managing bleeding and anticoagulant reversal. Nationwide Spanish multicenter Delphi method study with a panel of experts on anticoagulation and the management of bleeding. Two survey rounds were carried out between April and September 2015. Consensus was reached when more than 75% of the panelists scored items in the same tertile. Fifteen hematologists and 17 emergency medicine specialists from 14 Spanish autonomous communities participated. Consensus was reached on the use of both hemodialysis and an activated prothrombin complex concentrate (PCC) to antagonize significant/major bleeding in patients taking dabigatran. Use of an activated PCC was considered sufficient for patients on rivaroxaban or apixaban. The panel did not consider any PCC to be both effective and safe. Tests for activated partial thromboplastin, thrombin, diluted thrombin, and ecarin clotting times were considered useful in patients treated with dabigatran. A specific anti-Xa activity assay was suggested for patients who developed bleeds while treated with rivaroxaban or apixaban. Specific antidotes for direct-acting oral anticoagulants would be useful when severe bleeding occurs according to 97% of the panelists. Such antidotes would substantially change current treatment algorithms. The points of consensus were generally in line with clinical practice guidelines, but the Delphi process revealed that there are aspects of the clinical management of bleeding that require unified criteria. The need for specific antidotes for direct-acting oral anticoagulants was emphasized.

  8. Conservatively managed pineal apoplexy in an anticoagulated patient

    International Nuclear Information System (INIS)

    Werder, Gabriel M.; Razdan, Rahul S.; Gagliardi, Joseph A.; Chaddha, Shashi K.B.

    2008-01-01

    We present a case of pineal apoplexy in an anticoagulated and hypertensive 56-year-old Hispanic male. At presentation, the patient's international normalized ratio (INR) was 10.51 and his blood pressure was 200/130 mmHg. His presenting symptoms included acute onset of headache, chest pain, nausea, vomiting, vertigo, and visual disturbance. Neuroimaging demonstrated hemorrhage into a morphologically normal pineal gland. Under conservative management, the patient experienced gradual resolution of all symptoms excluding the disturbance of upward gaze

  9. Patients' preferences in anticoagulant therapy: discrete choice experiment.

    Science.gov (United States)

    Najafzadeh, Mehdi; Gagne, Joshua J; Choudhry, Niteesh K; Polinski, Jennifer M; Avorn, Jerry; Schneeweiss, Sebastian S

    2014-11-01

    With proliferating treatment options for anticoagulant therapy, physicians and patients must choose among them based on their benefits and risks. Using a Discrete Choice Experiment, we elicited patients' relative preferences for specific benefits and risks of anticoagulant therapy. We selected a sample of US patients with cardiovascular disease from an online panel and elicited their preferences for benefits and risks of anticoagulant therapy: nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, bleeding death, and need for monitoring. These attributes were used to design scenarios describing hypothetical treatments that were labeled as new drug, old drug, or no drug. Latent class analysis was used to identify groups of patients with similar preferences. A total of 341 patients completed all Discrete Choice Experiment questions. On average, patients valued a 1% increased risk of a fatal bleeding event the same as a 2% increase in nonfatal myocardial infarction, a 3% increase in nonfatal stroke, a 3% increase in cardiovascular death, a 6% increase in major bleeding, and a 16% increase in minor bleeding. The odds of choosing no drug or old drug versus new drug were 0.72 (95% confidence interval, 0.61-0.84) and 0.86 (95% confidence interval, 0.81-0.93), respectively. Previous stroke or myocardial infarction was associated with membership in the class with larger negative preferences for these outcomes. Patients' preferences for various outcomes of anticoagulant therapy vary and depend on their previous experiences with myocardial infarction or stroke. Incorporating these preferences into benefit risk calculation and treatment decisions can enhance patient-centered care. © 2014 American Heart Association, Inc.

  10. Radiation degradation of polysaccharides and induced biological activity

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, Naotsugu; Yoshii, Fumio; Makuuchi Keizo; Kume Tamikazu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Mitomo, Hiroshi [Gunma Univ., Kiryu (Japan). Faculty of Engineering

    1999-09-01

    Relationship between irradiation effect of polysaccharides and induced biological activity for plants has been investigated. Sodium alginate was irradiated by gamma-rays from a Co-60 source in liquid state (aqueous solution) and in solid state (powder form). Measurement of molecular weight and analysis of UV spectra of irradiated sodium alginate have been carried out. The molecular weight was decreased by irradiation in both conditions. New absorbance peak derived from double bond or/and carbonyl group was appeared at close to 267 nm by irradiation in UV spectra. It was found that alginate having molecular weight about 10,000 is most suitable to used as growth promoter in plants. To obtain the molecular weight of 10,000 by irradiation, the necessary doses are 100 kGy in liquid state and 500 kGy in solid state, respectively. (author)

  11. Helminth induced suppression of macrophage activation is correlated with inhibition of calcium channel activity.

    Directory of Open Access Journals (Sweden)

    Arun Chauhan

    Full Text Available Helminth parasites cause persistent infections in humans and yet many infected individuals are asymptomatic. Neurocysticercosis (NCC, a disease of the central nervous system (CNS caused by the cestode Taenia solium, has a long asymptomatic phase correlated with an absence of brain inflammation. However, the mechanisms of immune suppression remain poorly understood. Here we report that murine NCC displays a lack of cell surface maturation markers in infiltrating myeloid cells. Furthermore, soluble parasite ligands (PL failed to induce maturation of macrophages, and inhibited TLR-induced inflammatory cytokine production. Importantly, PL treatment abolished both LPS and thapsigargin-induced store operated Ca2+ entry (SOCE. Moreover, electrophysiological recordings demonstrated PL-mediated inhibition of LPS or Tg-induced currents that were TRPC1-dependent. Concomitantly STIM1-TRPC1 complex was also impaired that was essential for SOCE and sustained Ca2+ entry. Likewise loss of SOCE due to PL further inhibited NFkB activation. Overall, our results indicate that the negative regulation of agonist induced Ca2+ signaling pathway by parasite ligands may be a novel immune suppressive mechanism to block the initiation of the inflammatory response associated with helminth infections.

  12. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia-induced

  13. Evidence for an in vitro anticoagulant and antithrombotic activity in ...

    African Journals Online (AJOL)

    SERVER

    2008-03-18

    Mar 18, 2008 ... The inhibitory effect of processed garlic on human platelet aggregation has been known since 1978 (Lawson et al., 1992). According to. Mohammad and Woodward (1986), when an aqueous extract of garlic was added to platelet rich plasma (PRP), platelet aggregation was inhibited. These findings clearly.

  14. Antithrombotic/anticoagulant and anticancer activities of selected ...

    African Journals Online (AJOL)

    SERVER

    2008-02-05

    Feb 5, 2008 ... the synthesis of natural products and/or their derivatives, and new plant-derived medicines are continually being discovered (Van Wyk et al., 1997; De Medeiros et al.,. 2000; Rahman et al., 2001). Primary bioassay screens are important for the initial screening of plants for bioactive chemical constituents.

  15. New Direct Oral Anticoagulants (DOAC and Their Use Today

    Directory of Open Access Journals (Sweden)

    Heike Schwarb

    2016-03-01

    Full Text Available The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC, we now have an alternative to the traditional vitamin K antagonists (VKA for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.

  16. Spontaneous pharyngo-laryngeal hematoma and anticoagulation. A case report

    Directory of Open Access Journals (Sweden)

    Marleny CASASOLA-GIRÓN

    2016-03-01

    Full Text Available Introduction and Objective: Spontaneous pharyngeal-laryngeal hematoma shows the importance of a complete ENT examination in the face of symptoms of banal appearance and a correct history that, in the case reported, unveiled the therapeutic use of anticoagulants. Case description: A 55 year old woman comes to emergency because of unexplained dysphagia. The inspection shows the presence of a hematoma in the pharyngeal-laryngeal region that, after the anticoagulant therapy was reversed, evolved favorably with conservative treatment. Discussion: In this case, apart from medical management performed by the hematology department, we focus our therapeutic approach in the protection of the airway and the prevention of a possible massive bleeding. Determining which patients require endotracheal intubation or tracheostomy and hemostatic surgery is the key to treatment. Conclusions: The anticoagulant therapy involves several complications that ENT specialists must consider in the face of clinical symptoms of dysphagia, dysphonia, dyspnea or signs of bleeding and they must know the possibilities of performance depending on the severity of each case.

  17. [Oral anticoagulants and medicinal plants. An emerging interaction].

    Science.gov (United States)

    Argento, A; Tiraferri, E; Marzaloni, M

    2000-01-01

    The consumption of herbal medicines is increasing steadily throughout the world, although to our knowledge there are neither studies on their effectiveness nor controls over the quality and safety of these preparations. Considered "food integrators", these preparations are marketed without restriction. It is a common notion that natural therapy has neither side nor toxic effects: allergic reactions, direct toxic effects or those due to contamination, carcinogenicity, mutagenicity, and heavy metal toxicity have been reported as adverse events caused by herbs. Rather than replacing traditional therapy, most herbal medical treatment is used in conjunction with it. Also, the attending physician is generally not informed that the patient is using herbs. Because Passionflower, hydroalcoholic extracts, Juniper and Verbena officinalis supply variable quantities of vitamin K, they can lessen the effect of oral anticoagulant therapy. Ganoderma Japonicum, Papaw, Salvia miltiorrhiza, Ginseng, Devil's claw, Garlic, Quinine, Ginkgo, Ginger, Red Clover and Horse-Chestnut reinforce warfarin action by heterogeneous mechanisms. They should thus not be used in patients on oral anticoagulant and/or antiplatelet therapy. The scientific community must take into account the adverse events caused by interaction between herbal medicine and conventional therapy, and patients must be informed of the dangers of these preparations. If a bleeding event occurs or the quality of anticoagulant therapy is poor, the clinician should consider the possibility of interaction between conventional therapy and herbal medicine that the patient has neglected to mention he is taking.

  18. Electroconvulsive therapy and anticoagulation after pulmonary embolism: a case report

    Directory of Open Access Journals (Sweden)

    Julio Cesar Lazaro

    2014-07-01

    Full Text Available Introduction Electroconvulsive therapy (ECT is considered the most effective treatment for catatonia regardless its underlying condition. The rigid fixed posture and immobility observed in catatonia may lead to several clinical complications, of which, pulmonary embolism (PE is one of the most severe. The rapid improvement of the psychiatric condition in catatonia-related PE is essential, since immobility favors the occurrence of new thromboembolic events and further complications. In that scenario, ECT should be considered, based on a risk-benefit analysis, aiming at the faster resolution of the catatonia. Methods Case report and literature review. Results A 66-years-old woman admitted to the psychiatric ward with catatonia due to a depressive episode presented bilateral PE. Clinically stable, but still severely depressed after a trial of antidepressants, she was treated with ECT in the course of full anticoagulation with enoxaparin. After five ECT sessions, her mood was significantly better and she was walking and eating spontaneously. She did not present complications related either to PE or to anticoagulation. After the eighth ECT session, she evolved with hypomania, which was managed with oral medication adjustments. The patient was completely euthymic at discharge. Conclusion The case we presented provides further evidence to the anecdotal case reports on the safety of ECT in the course of concomitant full anticoagulant therapy after PE, and illustrates how, with the proper precautions, the benefits of ECT in such condition might outweigh its risks.

  19. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

    Science.gov (United States)

    Lee, Taewoo; Biddle, Andrea K.; Lionaki, Sofia; Derebail, Vimal K.; Barbour, Sean J.; Tannous, Sameer; Hladunewich, Michelle A.; Hu, Yichun; Poulton, Caroline J.; Mahoney, Shannon L.; Jennette, J. Charles; Hogan, Susan L.; Falk, Ronald J.; Cattran, Daniel C.; Reich, Heather N.; Nachman, Patrick H.

    2014-01-01

    Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (http://www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual’s needs and adaptable to dynamic changes in health status and risk profile. PMID:24336031

  20. Optimal Anticoagulation for Pregnant Women with Mechanical Heart Valves.

    Science.gov (United States)

    D'Souza, Rohan; Silversides, Candice K; McLintock, Claire

    2016-10-01

    The prothrombotic state of pregnancy increases the risk of thromboembolic complications and death in women with mechanical heart valves (MHVs). Although it is accepted that these women must be on therapeutic anticoagulation throughout pregnancy, competing maternal and fetal risks, as well as the lack of high-quality data from prospective studies, make the choice of the optimal method of anticoagulation challenging. Vitamin K antagonists (VKAs) are associated with fewer maternal complications, but conversely also the lowest live birth rates as well as warfarin-related embryopathy and fetopathy. Low-molecular-weight heparin (LMWH) does not cross the placenta and is associated with fewer fetal risks but more maternal complications. Sequential treatment involving VKAs in the second and third trimesters and either low-molecular-weight or unfractionated heparin in the first trimester, although appealing is still associated with maternal complications, especially around the time of bridging. As absolute equipoise of maternal versus fetal wellbeing is unlikely, patient preferences should be considered in decision making. A multidisciplinary team including hematologists, cardiologists, obstetric physicians, and high-risk obstetricians with expertise in the management of pregnant women with cardiac disease is required to optimize outcomes. Prospective studies are needed to determine the anticoagulant regimen for women with MHVs that provides optimal and acceptable maternal and fetal outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  2. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management.

    Science.gov (United States)

    Cheung, Ka-Shing; Leung, Wai K

    2017-03-21

    Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b.i.d), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.

  3. The role of heparin in sepsis: much more than just an anticoagulant.

    Science.gov (United States)

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  4. In vivo examination of the anticoagulant effect of the Brassica oleracea methanol extract

    Directory of Open Access Journals (Sweden)

    Khan Rafeeq Alam

    2015-01-01

    Full Text Available The anticoagulant effect of the methanol extract of Brassica oleracea var. capitata (MEB was examined in rabbits. The animals were divided into five groups, each comprising seven animals. Three groups were administered increasing doses of MEB (200, 300, and 500 mg/kg, respectively; one group received warfarin (0.54 mg/kg; animals in the control group received saline (1 ml/day equivalent to the volume of doses applied to the treated and standard animals. Biochemical tests were performed on the 16th and 31st days of dosing. Animals that were administered MEB (500 mg MEB/kg 30 days displayed increases of 24.07 s, 28.79 s and 4.08 s in activated partial thromboplastin (aPTT, fibrinogen (Fg and thrombin time (TT. Compared to the control, the increase in aPTT and Fg was highly significant and the increase in TT was significant. The anticoagulant effect exhibited by MEB in rabbits may be due to inactivation or inhibition of factors affecting coagulation.

  5. Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

    Science.gov (United States)

    Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

    2017-11-01

    Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

  6. Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro

    Science.gov (United States)

    Basavarajappa, Mallikarjuna S.; Karman, Bethany N.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2012-01-01

    Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48–96 h, MXC induced morphological atresia. At 24–96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles. PMID:23000595

  7. Irregular persistent activity induced by synaptic excitatory feedback

    Directory of Open Access Journals (Sweden)

    Francesca Barbieri

    2007-11-01

    Full Text Available Neurophysiological experiments on monkeys have reported highly irregular persistent activity during the performance of an oculomotor delayed-response task. These experiments show that during the delay period the coefficient of variation (CV of interspike intervals (ISI of prefrontal neurons is above 1, on average, and larger than during the fixation period. In the present paper, we show that this feature can be reproduced in a network in which persistent activity is induced by excitatory feedback, provided that (i the post-spike reset is close enough to threshold , (ii synaptic efficacies are a non-linear function of the pre-synaptic firing rate. Non-linearity between presynaptic rate and effective synaptic strength is implemented by a standard short-term depression mechanism (STD. First, we consider the simplest possible network with excitatory feedback: a fully connected homogeneous network of excitatory leaky integrate-and-fire neurons, using both numerical simulations and analytical techniques. The results are then confirmed in a network with selective excitatory neurons and inhibition. In both the cases there is a large range of values of the synaptic efficacies for which the statistics of firing of single cells is similar to experimental data.

  8. The European Heart Rhythm Association Practical Guide on the Use of New Oral Anticoagulants in Patients with Non-valvular Atrial Fibrillation – A Brief Summary

    Science.gov (United States)

    Kirchhof, Paulus

    2013-01-01

    New oral anticoagulants (NOACs) are an alternative to vitamin K antagonists (VKAs) in the prevention of stroke in patients with non-valvular atrial fibrillation (AF). The European Heart Rhythm Association (EHRA) has produced a practical guide to detail the use of NOACs in clinical practice. The guide includes a practical start-up and follow-up scheme, emphasising the importance of strict adherence to the regimen – the anticoagulant effect drops rapidly after 12–24 hours. There is also guidance on how to measure the anticoagulant effect of NOACs, switching between anticoagulant regimes and dealing with dosing errors. Physicians will have to consider the pharmacokinetic effect of drugs and co-morbidities when prescribing NOACs – plasma levels of NOACs may be affected by P-glycoprotein (P-gp) substrates, as well as cytochrome P450 (CYP3A4) inducers or inhibitors. In patients with chronic kidney disease, reduced doses of NOACs may be indicated. Guidance is also given on the management of bleeding complications, and the cessation and reinitiation of NOACs in patients undergoing surgical interventions. Finally, the use of NOACs in specific clinical situations is considered; these include patients with AF and coronary artery disease (CAD), patients presenting with acute stroke while taking NOACs and patients with cancer. PMID:26835051

  9. The European Heart Rhythm Association Practical Guide on the Use of New Oral Anticoagulants in Patients with Non-valvular Atrial Fibrillation - A Brief Summary.

    Science.gov (United States)

    Kirchhof, Paulus

    2013-11-01

    New oral anticoagulants (NOACs) are an alternative to vitamin K antagonists (VKAs) in the prevention of stroke in patients with non-valvular atrial fibrillation (AF). The European Heart Rhythm Association (EHRA) has produced a practical guide to detail the use of NOACs in clinical practice. The guide includes a practical start-up and follow-up scheme, emphasising the importance of strict adherence to the regimen - the anticoagulant effect drops rapidly after 12-24 hours. There is also guidance on how to measure the anticoagulant effect of NOACs, switching between anticoagulant regimes and dealing with dosing errors. Physicians will have to consider the pharmacokinetic effect of drugs and co-morbidities when prescribing NOACs - plasma levels of NOACs may be affected by P-glycoprotein (P-gp) substrates, as well as cytochrome P450 (CYP3A4) inducers or inhibitors. In patients with chronic kidney disease, reduced doses of NOACs may be indicated. Guidance is also given on the management of bleeding complications, and the cessation and reinitiation of NOACs in patients undergoing surgical interventions. Finally, the use of NOACs in specific clinical situations is considered; these include patients with AF and coronary artery disease (CAD), patients presenting with acute stroke while taking NOACs and patients with cancer.

  10. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    International Nuclear Information System (INIS)

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A.

    1990-01-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01)

  11. p38 Mitogen-Activated Protein Kinase in beryllium-induced dendritic cell activation.

    Science.gov (United States)

    Li, L; Huang, Z; Gillespie, M; Mroz, P M; Maier, L A

    2014-12-01

    Dendritic cells (DC) play a role in the regulation of immune responses to haptens, which in turn impact DC maturation. Whether beryllium (Be) is able to induce DC maturation and if this occurs via the MAPK pathway is not known. Primary monocyte-derived DCs (moDCs) models were generated from Be non-exposed healthy volunteers as a non-sensitized cell model, while PBMCs from BeS (Be sensitized) and CBD (chronic beryllium disease) were used as disease models. The response of these cells to Be was evaluated. The expression of CD40 was increased significantly (pBeSO₄-stimulation. BeSO₄ induced p38MAPK phosphorylation, while IκB-α was degraded in Be-stimulated moDCs. The p38 MAPK inhibitor SB203580 blocked Be-induced NF-κB activation in moDCs, suggesting that p38MAPK and NF-κB are dependently activated by BeSO₄. Furthermore, in BeS and CBD subjects, SB203580 downregulated Be-stimulated proliferation in a dose-dependent manner, and decreased Be-stimulated TNF-α and IFNγ cytokine production. Taken together, this study suggests that Be-induces non-sensitized Glu69+ DCs maturation, and that p38MAPK signaling is important in the Be-stimulated DCs activation as well as subsequent T cell proliferation and cytokine production in BeS and CBD. In total, the MAPK pathway may serve as a potential therapeutic target for human granulomatous lung diseases. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  12. Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Husted, Steen Elkjaer; Grove, Erik Lerkevang

    2016-01-01

    Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data...... on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes...... in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49...

  13. Candesartan ameliorates impaired fear extinction induced by innate immune activation.

    Science.gov (United States)

    Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T

    2016-02-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xue [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Tao [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai’an (China); Chen, Yuan [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Zhang, Kun [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); School of Life Science, Zhengzhou University, Zhengzhou (China); Maitz, Manfred F. [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Hohe Str. 06, 01069 Dresden (Germany); Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai’an (China); Chen, Junying, E-mail: chenjy@263.net [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Huang, Nan [Key Laboratory of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China)

    2014-11-30

    Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment.

  15. Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.

    Science.gov (United States)

    Li, Si-Wei; Feng, Xue; Xu, Hao; Chen, Ke-Ji

    2018-02-01

    To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer. Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument. For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (Phydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (Psodium. For high concentrations of puerarin (e.g. 3.8 mg/600 μL) and tirofiban hydrochloride (e.g. 0.8 μg/600 μL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance. Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.

  16. Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

    International Nuclear Information System (INIS)

    Wang, Xue; Liu, Tao; Chen, Yuan; Zhang, Kun; Maitz, Manfred F.; Pan, Changjiang; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment

  17. Effects of citrate-enriched bicarbonate based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients.

    Science.gov (United States)

    Rocha, Amanda D; Padua, Vanessa C; Oliveira, Esther; Guimaraes, Márcia M; Lugon, Jocemir R; Strogoff de Matos, Jorge P

    2014-04-01

    Systemic anticoagulation with unfractionated heparin is commonly used in maintenance hemodialysis (HD), but it increases the risk of bleeding complications. We investigated whether the use of citrate-enriched bicarbonate based dialysate (CD) would reduce systemic anticoagulation without compromising the efficacy of reprocessed dialyzers. This is a crossover study in which half of a total of 30 patients initially underwent HD with acetate-enriched bicarbonate based dialysate and a standard heparin dose of ∼ 100 IU/kg (Treatment A), whereas the remaining patients were treated with CD and a 30% reduced heparin dose (Treatment B). After 12 consecutive HD sessions in each treatment, the dialysate and heparin doses were reversed, then followed for another period of 12 HD sessions. The two treatment phases were split by a washout period of six HD sessions using acetate-enriched bicarbonate based dialysate and standard heparin dose. Systemic anticoagulation was higher in Treatment A. The activated partial thromboplastin time at the end of HD session was 68 ± 36 seconds in Treatment A and 47 ± 16 seconds in Treatment B (P = 0.005). Sixty-eight percent of the dialyzers remained adequate until the 12th use in Treatment A and 61% did so in Treatment B (P = 0.63). Patients had three and 24 cramps episodes during Treatment A and B, respectively (P < 0.001). Nine and 26 symptomatic intradialytic hypotension episodes were seen in Treatment A and B, respectively, (P = 0.003). In conclusion, the use of CD had a favorable effect on anticoagulation in the extracorporeal circuit in patients on maintenance HD, but it was also associated with more hypotension and cramps. © 2013 International Society for Hemodialysis.

  18. FOXO1 Regulates Bacteria-Induced Neutrophil Activity

    Directory of Open Access Journals (Sweden)

    Guangyu Dong

    2017-09-01

    Full Text Available Neutrophils play an essential role in the innate immune response to microbial infection and are particularly important in clearing bacterial infection. We investigated the role of the transcription factor FOXO1 in the response of neutrophils to bacterial challenge with Porphyromonas gingivalis in vivo and in vitro. In these experiments, the effect of lineage-specific FOXO1 deletion in LyzM.Cre+FOXO1L/L mice was compared with matched littermate controls. FOXO1 deletion negatively affected several critical aspects of neutrophil function in vivo including mobilization of neutrophils from the bone marrow (BM to the vasculature, recruitment of neutrophils to sites of bacterial inoculation, and clearance of bacteria. In vitro FOXO1 regulated neutrophil chemotaxis and bacterial killing. Moreover, bacteria-induced expression of CXCR2 and CD11b, which are essential for several aspects of neutrophil function, was dependent on FOXO1 in vivo and in vitro. Furthermore, FOXO1 directly interacted with the promoter regions of CXCR2 and CD11b. Bacteria-induced nuclear localization of FOXO1 was dependent upon toll-like receptor (TLR 2 and/or TLR4 and was significantly reduced by inhibitors of reactive oxygen species (ROS and nitric oxide synthase and deacetylases (Sirt1 and histone deacetylases. These studies show for the first time that FOXO1 activation by bacterial challenge is needed to mobilize neutrophils to transit from the BM to peripheral tissues in response to infection as well as for bacterial clearance in vivo. Moreover, FOXO1 regulates neutrophil function that facilitates chemotaxis, phagocytosis, and bacterial killing.

  19. Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human placental amino acid transport.

    Science.gov (United States)

    Kleppa, Marc-Jens; Erlenwein, Sarah-Vanessa; Darashchonak, Natallia; von Kaisenberg, Constantin S; von Versen-Höynck, Frauke

    2014-01-01

    Anticoagulants, e.g. low-molecular weight heparins (LMWHs) and acetylsalicylic acid (ASA) are prescribed to women at risk for pregnancy complications that are associated with impaired placentation and placental hypoxia. Beyond their role as anticoagulants these compounds exhibit direct effects on trophoblast but their impact on placental function is unknown. The amino acid transport systems A and L, which preferably transfer essential amino acids, are well-described models to study placental nutrient transport. We aimed to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental amino acid transport systems A and L and associated signalling mechanisms. The uptake of C14-MeAIB (system A) or H3-leucin (system L) was investigated after incubation of primary villous fragments isolated from term placentas. Villous tissue was incubated at 2% O2 (hypoxia), 8% O2 and standard culture conditions (21% O2) or at 2% O2 and 21% O2 with dalteparin or ASA. Activation of the JAK/STAT or mTOR signalling pathways was determined by Western analysis of total and phosphorylated STAT3 or Raptor. Hypoxia decreased system A mediated MeAIB uptake and increased system L mediated leucine uptake compared to standard culture conditions (21% O2). This was accompanied by an impairment of STAT3 and a stimulation of Raptor signalling. System L activity increased at 8% O2. Dalteparin treatment reduced system A and system L activity under normoxic conditions and ASA (1 mM) decreased system A and L transporter activity under normoxic and hypoxic conditions. Our data underline the dependency of placental function on oxygen supply. LMWHs and ASA are not able to reverse the effects of hypoxia on placental amino acid transport. These findings and the uncovering of the signalling mechanisms in more detail will help to understand the impact of LMWHs and ASA on placental function and fetal growth.

  20. Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human placental amino acid transport.

    Directory of Open Access Journals (Sweden)

    Marc-Jens Kleppa

    Full Text Available BACKGROUND: Anticoagulants, e.g. low-molecular weight heparins (LMWHs and acetylsalicylic acid (ASA are prescribed to women at risk for pregnancy complications that are associated with impaired placentation and placental hypoxia. Beyond their role as anticoagulants these compounds exhibit direct effects on trophoblast but their impact on placental function is unknown. The amino acid transport systems A and L, which preferably transfer essential amino acids, are well-described models to study placental nutrient transport. We aimed to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental amino acid transport systems A and L and associated signalling mechanisms. METHODS: The uptake of C14-MeAIB (system A or H3-leucin (system L was investigated after incubation of primary villous fragments isolated from term placentas. Villous tissue was incubated at 2% O2 (hypoxia, 8% O2 and standard culture conditions (21% O2 or at 2% O2 and 21% O2 with dalteparin or ASA. Activation of the JAK/STAT or mTOR signalling pathways was determined by Western analysis of total and phosphorylated STAT3 or Raptor. RESULTS: Hypoxia decreased system A mediated MeAIB uptake and increased system L mediated leucine uptake compared to standard culture conditions (21% O2. This was accompanied by an impairment of STAT3 and a stimulation of Raptor signalling. System L activity increased at 8% O2. Dalteparin treatment reduced system A and system L activity under normoxic conditions and ASA (1 mM decreased system A and L transporter activity under normoxic and hypoxic conditions. CONCLUSIONS: Our data underline the dependency of placental function on oxygen supply. LMWHs and ASA are not able to reverse the effects of hypoxia on placental amino acid transport. These findings and the uncovering of the signalling mechanisms in more detail will help to understand the impact of LMWHs and ASA on placental function and fetal growth.

  1. Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.

    Directory of Open Access Journals (Sweden)

    Junwei Yang

    Full Text Available Platelet-activating factor (PAF plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH, which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.

  2. Haemorrhagic cholecystitis in a newly anticoagulated patient.

    Science.gov (United States)

    Kinnear, Ned; Hennessey, Derek Barry; Thomas, Rebecca

    2017-04-12

    A 74-year-old man undergoing rehabilitation after pneumonia developed right upper quadrant abdominal pain. Five days earlier he had been commenced on apixaban for a new diagnosis of atrial fibrillation. Ultrasound and CT scans revealed an acalculous grossly thickened gallbladder, with high attenuation non-echogenic material both within and surrounding the structure. Active contrast extravasation was seen at the neck. On laparotomy, a perforated internally bleeding gallbladder containing a single calculus was found, with significant free blood within the abdomen. After cholecystectomy, the patient recovered slowly in hospital before nursing home placement. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. New anticoagulants: how to deal with treatment failure and bleeding complications.

    Science.gov (United States)

    Kazmi, Rashid S; Lwaleed, Bashir A

    2011-10-01

    Conventional anticoagulants have proven efficacy in the management of thromboembolism. Their adverse effects and a narrow therapeutic window, necessitating regular need for monitoring, however, have long been an incentive for the development of safer anticoagulants without compromising efficacy. Over the last decade or so several new parenteral and oral anticoagulants have been launched with efficacy comparable with conventional agents. From fondaparinux to its long acting derivative idraparinux, and the factor Xa inhibitor rivaroxaban to the direct thrombin inhibitor dabigatran, the advent of new anticoagulants is radically changing anticoagulation. For conventional anticoagulants, despite their shortcomings, effective methods of reversing their anticoagulant effects exist. Moreover, strategies to deal with the occurrence of fresh thrombotic events in the face of therapeutic anticoagulation with the conventional agents have also been addressed. Nevertheless, for the new anticoagulants, the optimal management of these complications remains unknown. This review explores these issues in the light of current evidence. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  4. Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

    Science.gov (United States)

    Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

    2017-08-01

    Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Major cerebral events in Staphylococcus aureus infective endocarditis: is anticoagulant therapy safe?

    DEFF Research Database (Denmark)

    Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars

    2009-01-01

    OBJECTIVES: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). METHODS: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset......-19%), and cerebral haemorrhage in 5 patients (3%; 95% CI: 0.5-6%). Patients receiving anticoagulation were less likely to have experienced a major cerebral event at the time of admission (15%) compared with those without anticoagulation (37%, p = 0.009; adjusted OR: 0.27; 95% CI: 0.075-0.96; p = 0.04). In...

  6. Postoperative anticoagulation in patients with mechanical heart valves following surgical treatment of subdural hematomas.

    Science.gov (United States)

    Amin, Anubhav G; Ng, Julie; Hsu, Wesley; Pradilla, Gustavo; Raza, Shaan; Quinones-Hinojosa, Alfredo; Lim, Michael

    2013-08-01

    Thromboembolic events and anticoagulation-associated bleeding events represent frequent complications following cardiac mechanical valve replacement. Management guidelines regarding the timing for resuming anticoagulation therapy following a surgically treated subdural hematoma (SDH) in patients with mechanical valves remains to be determined. To determine optimal anticoagulation management in patients with mechanical heart valves following treatment of SDH. Outcomes were retrospectively reviewed for 12 patients on anticoagulation therapy for thromboembolic prophylaxis for mechanical cardiac valves who underwent surgical intervention for a SDH at the Johns Hopkins Hospital between 1995 and 2010. The mean age at admission was 71 years. All patients had St. Jude's mechanical heart valves and were receiving anticoagulation therapy. All patients had their anticoagulation reversed with vitamin K and fresh frozen plasma and underwent surgical evacuation. Anticoagulation was withheld for a mean of 14 days upon admission and a mean of 9 days postoperatively. The average length of stay was 19 days. No deaths or thromboembolic events occurred during the hospitalization. Average follow-up time was 50 months, during which two patients had a recurrent SDH. No other associated morbidities occurred during follow-up. Interruptions in anticoagulation therapy for up to 3 weeks pose minimal thromboembolic risk in patients with mechanical heart valves. Close follow-up after discharge is highly recommended, as recurrent hemorrhages can occur several weeks after the resumption of anticoagulation.

  7. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity

    DEFF Research Database (Denmark)

    Köpper, Frederik; Bierwirth, Cathrin; Schön, Margarete

    2013-01-01

    DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (γH2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed...... knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation...... replication impaired by gemcitabine or by Chk1 inhibition. This rescue strictly depended on translesion DNA polymerases. In conclusion, instead of being an unavoidable consequence of DNA damage, alterations of replication speed and origin firing depend on MK2-mediated signaling....

  8. Noninvasive measurements of activity-induced changes in muscle metabolism.

    Science.gov (United States)

    McCully, K K; Kakihira, H; Vandenborne, K; Kent-Braun, J

    1991-01-01

    Two noninvasive measurement techniques were used to monitor activity-induced changes in skeletal muscle in humans. Phosphorus magnetic resonance spectroscopy (P-MRS) was used to measure changes in energy metabolism by measuring the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) during steady level work in the wrist flexor muscles in a 30 cm bore, 1.9 Telsa magnet, and the rate of PCr recovery from exercise in the calf muscles in a 76 cm bore, 1.8 Tesla magnet. Near red spectroscopy (NRS) was used to measure changes in oxygen saturation of hemoglobin and myoglobin during and after exercise. Fourteen days of wrist flexion exercise resulted in significant improvement in muscle metabolism as measured by MRS. This improvement disappeared after 35 days of inactivity. Indications of muscle stress during training such as muscle soreness and decreased maximum strength were associated with increases in resting Pi/PCr. A similar training protocol using plantar flexion exercise resulted in an improved rate of PCr resynthesis, which returned to control values 42 days after training stopped. NRS measurements of the wrist flexor muscles during a ramp exercise protocol demonstrated a decrease in the oxygen saturation of hemoglobin-myoglobin from 60% at rest to 15% at the highest work levels. The half time of recovery of oxygen saturation was faster than that of PCr in both young and old subjects, supporting the hypothesis that oxygen delivery is not rate limiting in submaximal exercise in healthy individuals.

  9. Patients' knowledge on oral anticoagulant treatment in Hungary.

    Science.gov (United States)

    Viola, Reka; Fekete, Helga; Csoka, Ildiko

    2017-12-01

    Background A key element for an effective and safe oral anticoagulant treatment (OAT) is to have the relevant information delivered to patients in an easy-to-understand way and thus have them apply this knowledge in their own therapy. Objective To assess knowledge about OAT, reveal knowledge gaps and identify at-risk patients in terms of limited knowledge about their anticoagulant therapy. Setting Community pharmacies in Hungary. Methods This descriptive cross-sectional study used a structured, validated, self-developed questionnaire to assess patients' knowledge about OAT. Scores were calculated on each domain and the association between knowledge and patients' or treatment characteristics were analysed. Responses in all domains were assessed to identify at-risk patients and knowledge gaps. Main outcome measures Knowledge and knowledge gaps on OAT, and risk factors for limited knowledge. Results The questionnaire developed based on four validated questionnaires passed the field test and had a good internal consistency (Cronbach α = 0.795). Our full patient population (N = 427) had a mean percentage score of 59.39 (29.7% good, 41.2% average, 29.0% poor knowledge on OAT). Poor knowledge level was found to significantly correlate with advanced age (> 75 years), lower education, diagnosis of atrial fibrillation, and unawareness of the indication of OAT. The lowest frequency of correct answers regarded the questions on drug interactions (10.2%) and diet (11.4%). Pharmacists were infrequently indicated as the healthcare professionals to share information with regarding OAT (12.7%). Conclusion Findings of our study offer a valuable insight into the required directions of developing new strategies for patient education to improve knowledge on the treatment with oral anticoagulants.

  10. Anticoagulation in heart failure: current status and future direction.

    Science.gov (United States)

    Gheorghiade, Mihai; Vaduganathan, Muthiah; Fonarow, Gregg C; Greene, Stephen J; Greenberg, Barry H; Liu, Peter P; Massie, Barry M; Mehra, Mandeep R; Metra, Marco; Zannad, Faiez; Cleland, John G F; van Veldhuisen, Dirk J; Shah, Ami N; Butler, Javed

    2013-11-01

    Despite therapeutic advances, patients with worsening heart failure (HF) requiring hospitalization have unacceptably high post-discharge mortality and re-admission rates soon after discharge. Evidence suggests a hypercoagulable state is present in patients with HF. Although thromboembolism as a direct consequence of HF is not frequently clinically recognized, it may contribute to mortality and morbidity. Additionally, many patients with HF have concomitant disorders conferring additional thrombotic risk, including atrial fibrillation (AF) and coronary artery disease (CAD). Acute coronary syndrome (ACS), a known consequence of coronary thrombosis, is a common precipitating factor for worsening HF. Coronary thrombosis may also cause sudden death in patients with HF and CAD. Because data are largely derived from observational studies or trials of modest size, guideline recommendations on anticoagulation for HF vary between organizations. The recently presented Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial of HF patients in sinus rhythm suggested anticoagulation reduces the risk of stroke, although rates of the combined primary endpoint (death, ischemic stroke, or intracerebral hemorrhage) were similar for acetylsalicylic acid and warfarin. Newer oral anticoagulants dabigatran, apixaban, and rivaroxaban have successfully completed trials for the prevention of stroke in patients with AF and have shown benefits in the subpopulation of patients with concomitant HF. Positive results of the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51) trial of rivaroxaban in ACS are also encouraging. These data suggest there is a need to assess the potential role for these newer agents in the management of patients hospitalized for HF who continue to have a high post-discharge event rate despite available therapies.

  11. Trace elements induce predominance among methanogenic activity in anaerobic digestion

    Directory of Open Access Journals (Sweden)

    Babett Wintsche

    2016-12-01

    Full Text Available Trace elements play an essential role in all organisms due to their functions in enzyme complexes. In anaerobic digesters, control and supplementation of trace elements lead to stable and more efficient methane production processes while trace element deficits cause process imbalances. However, the underlying metabolic mechanisms and the adaptation of the affected microbial communities to such deficits are not yet fully understood. Here, we investigated the microbial community dynamics and resulting process changes induced by trace element deprivation. Two identical lab-scale continuous stirred tank reactors fed with distiller’s grains and supplemented with trace elements (cobalt, molybdenum, nickel, tungsten and a commercial iron additive were operated in parallel. After 72 weeks of identical operation, the feeding regime of one reactor was changed by omitting trace element supplements and reducing the amount of iron additive. Both reactors were operated for further 21 weeks. Various process parameters (biogas production and composition, total solids and volatile solids, trace element concentration, volatile fatty acids, total ammonium nitrogen, total organic acids/alkalinity ratio, and pH and the composition and activity of the microbial communities were monitored over the total experimental time. While the methane yield remained stable, the concentrations of hydrogen sulfide, total ammonia nitrogen, and acetate increased in the trace element-depleted reactor compared to the well-supplied control reactor. Methanosarcina and Methanoculleus dominated the methanogenic communities in both reactors. However, the activity ratio of these two genera was shown to depend on trace element supplementation explainable by different trace element requirements of their energy conservation systems. Methanosarcina dominated the well-supplied anaerobic digester, pointing to acetoclastic methanogenesis as the dominant methanogenic pathway. Under trace element

  12. Increased use of oral anticoagulants in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Gadsbøll, Kasper; Staerk, Laila; Fosbøl, Emil Loldrup

    2017-01-01

    Aim The aim of this study is to examine temporal trends in the use oral anticoagulants (OAC) as stroke prophylaxis in patients with atrial fibrillation (AF) and to examine factors associated with OAC initiation. Methods and results From Danish nationwide registries, we identified patients diagnosed...... initiation rates increased (P age > 75 years and high risk of stroke). The increased OAC...... initiation was accompanied by introduction and increased uptake of the NOACs. By the end of the study, NOACs accounted for 72.5% of all OACs prescribed in newly diagnosed AF patients. OAC initiation was associated with male gender, age 65-74 years, few comorbidities and increased risk of stroke. Conclusion...

  13. Direct Oral Anticoagulant Drugs in Dental Clinical Practice

    Directory of Open Access Journals (Sweden)

    Stasko J.

    2017-08-01

    Full Text Available The direct oral anticoagulant drugs (DOAC are generally safe and effective in several clinical settings including acute venous thromboembolic disease, prophylaxis in the postoperative setting, prevention of thromboembolism in patients with non-valvular atrial fibrillation, and in the management of acute coronary syndrome. The relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use of the DOAC. The aim of this work is to propose and summarize periprocedural management of patients treated with the DOAC in dental practice and to inform about the principal specifications of this treatment.

  14. Novel oral anticoagulants for stroke prevention in atrial fibrillation

    DEFF Research Database (Denmark)

    Lip, Gregory Y H; Bongiorni, Maria Grazia; Dobreanu, Dan

    2013-01-01

    The purpose of this European Heart Rhythm Association (EHRA) survey was to assess clinical practice in relation to stroke prevention in atrial fibrillation (AF), particularly into the use of novel oral anticoagulants (NOACs) for stroke prevention, among members of the EHRA electrophysiology (EP......) research network. In this EP Wire survey, we have provided some insights into current practice in Europe for the use of NOACs for stroke prevention in AF. There were clear practice differences evident, and also the need for greater adherence to the guidelines, especially since guideline adherent management...

  15. Anticoagulation Quality and Complications of using Vitamin K Antagonists in the Cardiac Surgery Outpatient Clinic

    Directory of Open Access Journals (Sweden)

    Mário Augusto Cray da Costa

    Full Text Available ABSTRACT Introduction: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. Objective: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. Methods: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. Results: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli; 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001. Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04. Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03, less annual consultations (P=0.02 and less dose adjustments (P=0.003. Patients with longer duration of anticoagulation have more complications (P=0.001. Conclusion: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of

  16. Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N

    2013-01-01

    682753A, which blocks oxysterol-induced G-protein activation, β-arrestin recruitment and B-cell chemotaxis. We furthermore demonstrate that activation triggers pertussis toxin-sensitive MAP kinase phosphorylation, which is also inhibited by GSK682753A. Thus, EBI2 signalling in B cells mediates key...

  17. IKK/NF-κB-dependent satellite glia activation induces spinal cord microglia activation and neuropathic pain after nerve injury.

    Science.gov (United States)

    Lim, Hyoungsub; Lee, Hyunkyoung; Noh, Kyungchul; Lee, Sung Joong

    2017-09-01

    Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice. In addition, nerve injury-induced proinflammatory gene expression and macrophage infiltration into the dorsal root ganglion (DRG) were severely compromised. However, macrophages recruited into the DRG had minimal effects on spinal cord microglia activation, suggesting a causal effect for SGC activation on spinal cord microglia activation. In an effort to elucidate the molecular mechanisms, we measured Csf1 expression in the DRG, which is implicated in spinal cord microglia activation after nerve injury. In cIkkβ mice, nerve injury-induced Csf1 upregulation was ameliorated indicating that IKK/NF-κΒ-dependent SGC activation induced Csf1 expression in sensory neurons. Taken together, our data suggest that nerve injury-induced SGC activation triggers Csf1 induction in sensory neurons, spinal cord microglia activation, and subsequent central pain sensitization.

  18. Study on antithrombotic and antiplatelet activities of low molecular weight fucoidan from Laminaria japonica

    Science.gov (United States)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue

    2012-06-01

    The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.

  19. Computation of induced electric field for the sacral nerve activation

    International Nuclear Information System (INIS)

    Hirata, Akimasa; Hattori, Junya; Laakso, Ilkka; Takagi, Airi; Shimada, Takuo

    2013-01-01

    The induced electric field/current in the sacral nerve by stimulation devices for the treatment of bladder overactivity is investigated. Implanted and transcutaneous electrode configurations are considered. The electric field induced in the sacral nerve by the implanted electrode is largely affected by its surrounding tissues, which is attributable to the variation in the input impedance of the electrode. In contrast, the electric field induced by the transcutaneous electrode is affected by the tissue conductivity and anatomical composition of the body. In addition, the electric field induced in the subcutaneous fat in close proximity of the electrode is comparable with the estimated threshold electric field for pain. These computational findings explain the clinically observed weakness and side effect of each configuration. For the transcutaneous stimulator, we suggest that the electrode contact area be increased to reduce the induced electric field in the subcutaneous fat. (paper)

  20. Potential Use of Polysaccharides from the Brown Alga Undaria pinnatifida as Anticoagulants

    Directory of Open Access Journals (Sweden)

    Caterina Faggio

    2015-10-01

    Full Text Available Undaria pinnatifida (U. pinnatifida is a highly invasive species and has caused concern all over the world because it has invaded coastal environments, has the potential to displace native species, significantly alters habitat for associated fauna, and disturbs navigation. Any attempt to eradicate it would be futile, owing to the elusive, microscopic gametophyte, and because the alga thrives in sites rich in anthropic activities. Venice Lagoon is the largest Mediterranean transitional environment and the spot of the highest introduction of non-indigenous species, including U. pinnatifida, which is removed as a waste. We demonstrated that polysaccharide extracts from U. pinnatifida have an anticoagulant effect on human blood in vitro and are not cytotoxic. The results obtained by PT (normal values 70-120% and APTT (normal values 28-40s assays were significantly prolonged by the polysaccharide extracts of U. pinnatifida, therefore algal extracts are ideal candidates as antithrombotic agents.

  1. INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

    Science.gov (United States)

    Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

    2012-04-01

    Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

  2. Warfarin anticoagulation in hemodialysis patients with atrial fibrillation: comparison of nephrologist-led and anticoagulation clinic-led management.

    Science.gov (United States)

    Bahbahani, Hamad; AlTurki, Ahmed; Dawas, Ahmed; Lipman, Mark L

    2018-01-08

    There is conflicting evidence of benefit versus harm for warfarin anticoagulation in hemodialysis patients with atrial fibrillation. This equipoise may be explained by suboptimal Time in Therapeutic Range (TTR), which correlates well with thromboembolic and bleeding complications. This study aimed to compare nephrologist-led management of warfarin therapy versus that led by specialized anticoagulation clinic. In a retrospective cohort of chronic hemodialysis patients from two institutions (Institution A: Nephrologist-led warfarin management, Institution B: Anticoagulation clinic-led warfarin management), we identified patients with atrial fibrillation who were receiving warfarin for thromboembolic prophylaxis. Mean TTRs, proportion of patients achieving TTR ≥ 60%, and frequency of INR testing were compared using a logistic regression model. In Institution A, 16.7% of hemodialysis patients had atrial fibrillation, of whom 36.8% were on warfarin. In Institution B, 18% of hemodialysis patients had atrial fibrillation, and 55.5% were on warfarin. The mean TTR was 61.8% (SD 14.5) in Institution A, and 60.5% (SD 15.8) in Institution B (p-value 0.95). However, the proportion of patients achieving TTR ≥ 60% was 65% versus 43.3% (Adjusted OR 2.22, CI 0.65-7.63) and mean frequency of INR testing was every 6 days versus every 13.9 days in Institutions A and B respectively. There was no statistical difference in mean TTR between nephrologist-led management of warfarin and that of clinic-led management. However, the former achieved a trend toward a higher proportion of patients with optimal TTR. This improved therapeutic results was associated with more frequent INR monitoring.

  3. Does novel oral anticoagulant improve anticoagulation for non-valvular atrial fibrillation associated stroke: An inpatient registration study in Shanghai

    Directory of Open Access Journals (Sweden)

    Feng-Di Liu

    2015-12-01

    Full Text Available Abstracts: Objective: To summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA prevention, and reasons for not using dabigatran etexilate (DE in Shanghai, China. Methods: Non-valvular atrial fibrillation (NVAF-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed. Patients: From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography. Results: Before introduction of DE (April 2013, use rates of warfarin and antiplatelets were 28.9% (11/38 and 60.5% (23/38 respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72, 12.5% (9/72, and 43.1% (31/72. The DE did not improve use of anticoagulants (P = 0.639. There were 19 (17.3% recurrent ischemic stroke events up to October 2015; two (9.5% in the non-user group, 10 (18.5% in the antiplatelet group, and seven (20.0% in the anticoagulants group (P = 0.570. Furthermore, recurrence rates were similar between the DE group (20.0% and the Warfarin group (20.0%, P = 1.000. The most common reason for not using DE was financial concerns (61.0%, followed by inconvenience to purchase (14.0% and hemorrhage concerns (11.0%. Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux from DE. Conclusion: The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance. Keywords

  4. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    Directory of Open Access Journals (Sweden)

    Hisanao Akiyama

    Full Text Available The first non-vitamin K antagonist oral anticoagulant (NOAC introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH.We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014.ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years. Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy.

  5. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    Science.gov (United States)

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  6. Anticoagulation in atrial fibrillation. Is there a gap in care for ambulatory patients?

    Science.gov (United States)

    Putnam, Wayne; Nicol, Kelly; Anderson, David; Brownell, Brenda; Chiasson, Meredith; Burge, Frederick I.; Flowerdew, Gordon; Cox, Jafna

    2004-01-01

    OBJECTIVE: Atrial fibrillation (AF) substantially increases risk of stroke. Evidence suggests that anticoagulation to reduce risk is underused (a "care gap"). Our objectives were to clarify measures of this gap in care by including data from family physicians and to determine why eligible patients were not receiving anticoagulation therapy. DESIGN: Telephone survey of family physicians regarding specific patients in their practices. SETTING: Nova Scotia. PARTICIPANTS: Ambulatory AF patients not taking warfarin who had risk factors that made anticoagulation appropriate. MAIN OUTCOME MEASURES: Proportion of patients removed from the care gap; reasons given for not giving the remainder anticoagulants. RESULTS: Half the patients thought to be in the care gap had previously unknown contraindications to anticoagulation, lacked a clear indication for anticoagulation, or were taking warfarin. Patients' refusal and anticipated problems with compliance and monitoring were among the reasons for not giving patients anticoagulants. CONCLUSION: Adding data from primary care physicians significantly narrowed the care gap. Attention should focus on the remaining reasons for not giving eligible patients anticoagulants. PMID:15508374

  7. Safety and efficacy of anticoagulation for secondary stroke prevention in atrial fibrillation patients: The AMADEUS trial

    NARCIS (Netherlands)

    Lane, D.A.; Kamphuisen, P.W.; Minini, P.; Buller, H.R.; Lip, G.Y.H.

    2010-01-01

    ackground: Patients with atrial fibrillation (AF) and previous ischemic stroke are at high risk of recurrent stroke, but are also perceived to be at increased bleeding risk while treated with anticoagulants. Methods: Post-hoc analyses examined the efficacy and safety of anticoagulation of 4576 AF

  8. Conservative approach to dental extractions in patients on anticoagulant therapy: A clinical study.

    Science.gov (United States)

    Somma, Francesco; Grande, Nicola Maria; Plotino, GianLuca; Cameli, Giorgio; Pameijer, Cornelis H

    2010-01-01

    This clinical study reviewed dental surgical extractions that were performed on 532 patients diagnosed at risk of thromboembolism without interrupting their anticoagulant therapy. The results confirmed that anticoagulant therapy can be modified successfully and does not need to be interrupted, which can carry significant risks.

  9. Comparing Direct Oral Anticoagulants and Warfarin for Atrial Fibrillation, Venous Thromboembolism, and Mechanical Heart Valves.

    Science.gov (United States)

    Marcy, Todd R; Truong, Teresa; Rai, Andrea

    2015-11-01

    To summarize available data for use of direct oral anticoagulants in nonvalvular atrial fibrillation, venous thromboembolism, and mechanical heart valves including dose-response consistency to offer considerations for pharmacotherapeutic decision-making for oral anticoagulants. A Medline search of English-language studies published between 2000 and March 2015 was conducted to identify pertinent papers using combinations of the following words: apixaban, atrial fibrillation, dabigatran, direct oral anticoagulant, edoxaban, factor IIa inhibitors, factor Xa inhibitors, mechanical heart valves, novel oral anticoagulant, rivaroxaban, venous thromboembolism, and warfarin. Original studies, guidelines, and approved prescribing information were evaluated and included if contributing new or complementary data toward the objective. References for all identified studies were reviewed and entries included if contributory. Randomized controlled trials have established the safety and efficacy of direct oral anticoagulants in atrial fibrillation and venous thromboembolism for most patient groups. Direct oral anticoagulants should not be used in patients with mechanical heart valves until proven safe and effective. There are groups for which questions remain regarding inter-patient dose-response consistency for direct oral anticoagulants. There are postmarketing data suggesting poorer real-world performance of dabigatran relative to clinical trial data. Direct oral anticoagulants offer several advantages over warfarin, and large clinical trial data establish the appropriateness of their use in broad populations. There remain groups for whom the relative benefit and risk of these agents relative to warfarin are uncertain. A patient-specific approach in pharmacotherapeutic decision-making is appropriate.

  10. The use of prophylactic anticoagulation during induction and consolidation chemotherapy in adults with acute lymphoblastic leukemia.

    Science.gov (United States)

    Grace, Rachael F; DeAngelo, Daniel J; Stevenson, Kristen E; Neuberg, Donna; Sallan, Stephen E; Mourad, Yasser R Abou; Bergeron, Julie; Seftel, Matthew D; Kokulis, Caroline; Connors, Jean M

    2018-02-01

    Treatment for acute lymphoblastic leukemia (ALL) in adults confers a high risk of venous thromboembolic (VTE) complications. We describe the implementation and results of prophylactic anticoagulation guidelines in adults (18-50 years) treated on a Dana-Farber Cancer Institute ALL pediatric inspired consortium protocol from 2007 to 2013. A high rate of asparaginase related toxicity events, including thrombosis, resulted in a protocol amendment adding guidelines for prophylactic anticoagulation and a modified asparaginase dose and schedule. After excluding patients with Philadelphia positive ALL, a cohort of 36 patients were treated after the protocol amendment with prophylactic anticoagulation and compared to 49 patients who received no prophylactic anticoagulation. Bleeding complications were not significantly different in those treated with prophylactic anticoagulation compared with those enrolled prior to the amendment (p = 0.26). No patients on prophylactic anticoagulation had grade ≥ 3 bleeding. Prior to the amendment, the 2 year cumulative incidence of VTE post-induction was 41% compared to 28% while on prophylactic anticoagulation (p = 0.32). The 2 year cumulative incidence pulmonary embolus pre-amendment was 16% compared with 8% post-amendment (p = 0.34). Prophylactic anticoagulation can be safely administered to adults with ALL without increasing the number or severity of bleeding events and, in addition to modifications in the asparaginase regimen, resulted in a reduction in the cumulative incidence of VTE.

  11. Self-monitoring and self-management of oral anticoagulation.

    Science.gov (United States)

    Heneghan, Carl J; Garcia-Alamino, Josep M; Spencer, Elizabeth A; Ward, Alison M; Perera, Rafael; Bankhead, Clare; Alonso-Coello, Pablo; Fitzmaurice, David; Mahtani, Kamal R; Onakpoya, Igho J

    2016-07-05

    The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0

  12. Evidence of solar induced cycles of high seismic activity

    Science.gov (United States)

    Duma, G.

    2010-12-01

    100 with Kp. In terms of earthquake statistics, the changes of Kp imply that in N-America during Kp maxima there happen e.g. 1 event M7, 4 events M6 and 30 events M5 per year, instead of only 10 events M5 in years with lowest Kp. For S-America the number of events during Kp maxima is about twice that observed for N-America. It further turns out that in all three regions, the strongest earthquakes with magnitude 7 and even 8 occur during the Kp maxima. In the recent decade, several geophysical models have been tested at the ZAMG and in co-operation with institutes in USA and UK, to interpret the coupling between the solar induced geomagnetic variations and disturbances and its mechanic implications in the Earth’s lithosphere, i.e. in rupture zones. Two such models are briefly introduced, which fit well the observations and indicate high mechanic forces due to electromagnetic induction. The described solar-terrestrial effect significantly affects strong earthquake activity, as outlined above. It is a general geodynamic process which acts in nearly all main seismic regions on the globe. Thus, the results may essentially contribute to a better understanding of earthquake occurrence and hazard assessment.

  13. When and in which patients can anticoagulation be resumed after intracerebral haemorrhage?

    Directory of Open Access Journals (Sweden)

    Marco Marietta

    2011-08-01

    Full Text Available Whether to resume the anticoagulant or the antiaggregant therapy after an episode of major haemorrhage is a difficult dilemma for the physician. The physician has to take into consideration two major questions: whether the benefits of restarting anticoagulation outweigh the risk, and if so, when and how should anticoagulation be restarted. Although some case reports suggest that anticoagulation can be withheld safely for short periods after ICH, even in patients with mechanical heart valves, it is still not clear if long-term anticoagulation can be safely reinstituted after haemorrhage, for example in patients with atrial fibrillation. In fact, no large and well-conducted randomised clinical trials are available, and there is lack of strong evidence on which guidelines recommendations can be based. The article summarise the available literature findings. Finally, a protocol is suggested which may represent a useful tool for assessing treatment options.

  14. Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release.

    Science.gov (United States)

    Martín-Sánchez, Fátima; Martínez-García, Juan José; Muñoz-García, María; Martínez-Villanueva, Miriam; Noguera-Velasco, José A; Andreu, David; Rivas, Luís; Pelegrín, Pablo

    2017-08-10

    The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin domain 3 (NLRP3) inflammasome is a sensor for different types of infections and alterations of homeostatic parameters, including abnormally high levels of the extracellular nucleotide ATP or crystallization of different metabolites. All NLRP3 activators trigger a similar intracellular pathway, where a decrease in intracellular K + concentration and permeabilization of plasma membrane are key steps. Cationic amphipathic antimicrobial peptides and peptide toxins permeabilize the plasma membrane. In fact, some of them have been described to activate the NLRP3 inflammasome. Among them, the bee venom antimicrobial toxin peptide melittin is known to elicit an inflammatory reaction via the NLRP3 inflammasome in response to bee venom. Our study found that melittin induces canonical NLRP3 inflammasome activation by plasma membrane permeabilization and a reduction in the intracellular K + concentration. Following melittin treatment, the apoptosis-associated speck-like protein, an adaptor protein with a caspase recruitment domain (ASC), was necessary to activate caspase-1 and induce IL-1β release. However, cell death induced by melittin prevented the formation of large ASC aggregates, amplification of caspase-1 activation, IL-18 release and execution of pyroptosis. Therefore, melittin-induced activation of the NLRP3 inflammasome results in an attenuated inflammasome response that does not result in caspase-1 dependent cell death.

  15. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells

    Science.gov (United States)

    Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-01-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

  16. Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Shiguang [Department of Intensive Care Unit, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Mao, Li [Department of Endocrinology, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Ji, Feng, E-mail: huaiaifengjidr@163.com [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Shouguo; Xie, Yue; Fei, Haodong [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Xiao-dong, E-mail: xiaodongwangsz@163.com [The Center of Diagnosis and Treatment for Children' s Bone Diseases, The Children' s Hospital Affiliated to Soochow University, Suzhou (China)

    2016-03-18

    Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.

  17. Peroxisome proliferator-activated receptor α activation induces hepatic steatosis, suggesting an adverse effect.

    Directory of Open Access Journals (Sweden)

    Fang Yan

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by hepatic triglyceride accumulation, ranging from steatosis to steatohepatitis and cirrhosis. NAFLD is a risk factor for cardiovascular diseases and is associated with metabolic syndrome. Antihyperlipidemic drugs are recommended as part of the treatment for NAFLD patients. Although fibrates activate peroxisome proliferator-activated receptor α (PPARα, leading to the reduction of serum triglyceride levels, the effects of these drugs on NAFLD remain controversial. Clinical studies have reported that PPARα activation does not improve hepatic steatosis. In the present study, we focused on exploring the effect and mechanism of PPARα activation on hepatic triglyceride accumulation and hepatic steatosis. Male C57BL/6J mice, Pparα-null mice and HepG2 cells were treated with fenofibrate, one of the most commonly used fibrate drugs. Both low and high doses of fenofibrate were administered. Hepatic steatosis was detected through oil red O staining and electron microscopy. Notably, in fenofibrate-treated mice, the serum triglyceride levels were reduced and the hepatic triglyceride content was increased in a dose-dependent manner. Oil red O staining of liver sections demonstrated that fenofibrate-fed mice accumulated abundant neutral lipids. Fenofibrate also increased the intracellular triglyceride content in HepG2 cells. The expression of sterol regulatory element-binding protein 1c (SREBP-1c and the key genes associated with lipogenesis were increased in fenofibrate-treated mouse livers and HepG2 cells in a dose-dependent manner. However, the effect was strongly impaired in Pparα-null mice treated with fenofibrate. Fenofibrate treatment induced mature SREBP-1c expression via the direct binding of PPARα to the DR1 motif of the SREBP-1c gene. Taken together, these findings indicate the molecular mechanism by which PPARα activation increases liver triglyceride accumulation and suggest an

  18. Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice

    NARCIS (Netherlands)

    Waasdorp, Maaike; Duitman, Janwillem; Florquin, Sandrine; Spek, C. Arnold

    2016-01-01

    Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and

  19. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    Science.gov (United States)

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  20. Management dilemmas in patients with mechanical heart valves and warfarin-induced major bleeding.

    Science.gov (United States)

    Panduranga, Prashanth; Al-Mukhaini, Mohammed; Al-Muslahi, Muhanna; Haque, Mohammed A; Shehab, Abdullah

    2012-03-26

    Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging. There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism. Presently, the treatments available to reverse warfarin-induced bleeding are vitamin K, fresh frozen plasma, prothrombin complex concentrates and recombinant activated factor VIIa. Currently, vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding. The safe use of prothrombin complex concentrates and recombinant activated factor VIIa in patients with mechanical heart valves is controversial and needs well-designed clinical studies. With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves, the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed. In this review article, we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve. Furthermore, there is an urgent need for separate specific guidelines from major associations/ professional societies with regard to mechanical heart valves and warfarin-induced bleeding.

  1. IMPACT OF ANTICOAGULANT THERAPY ON THE INDICATORS OF ARTERIAL STIFFNESS AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ATRIAL FIBRILLATION AFTER CARDIOEMBOLIC STROKE

    Directory of Open Access Journals (Sweden)

    I. A. Zolotovskaya

    2016-01-01

    Full Text Available Objective: to investigate the impact of anticoagulant therapy on the indicators of arterial stiffness and endothelial dysfunction (ED in patients with atrial fibrillation (AF after cardioembolic stroke (CES.Patients and methods. The investigation enrolled 93 patients with AF after CES. The patients were divided into two groups: a study group in which all patients (n=48 received anticoagulants and a comparison group (n=45 in which the patients did not take anticoagulants, although the latter had been prescribed. The follow-up duration was 180.5±5.5 days. During this time the patients visited their doctors twice: the first visit was at baseline, the second one was after 24 weeks.All the patients underwent three-dimensional sphygmography. The levels of glucose, creatinine, total cholesterol, high-density lipoproteins, and triglycerides were determined. The markers of endothelial function, such as von Willebrand factor, plasminogen, antithrombin III,  and tissue plasminogen activator inhibitor-1, were estimated.Results. All the patients in the study and comparison groups had a higher comorbidity index of obvious somatic pathology. The patients from both groups showed changes in all cardiac morphometric and functional parameters. It was noted that after 6 months of a follow-up, there was a statistically significant positive trend in the indicators of arterial stiffness in the patients taking anticoagulants. The study group showed a significant correlation of blood pressure with the argumentation index. The 6-month follow-up revealed a strong correlation between the cardioankle vascular index and all the indicators of ED in the study group. After 24 weeks, in both groups there were 12 (12.9% deaths: 3 (6.25% and 8 (17.8% in the study and comparison groups, respectively.Conclusion. The findings suggest that in patients with AF after CES, the indicators of arterial stiffness and endothelial function tend to improve during anticoagulant therapy.

  2. Effects of alliin on LPS-induced acute lung injury by activating PPARγ.

    Science.gov (United States)

    Wang, Yi-Luan; Guo, Xian-Yang; He, Wei; Chen, Ru-Jie; Zhuang, Rong

    2017-09-01

    Alliin is a garlic organosulfur compound that possesses various pharmacological properties. In the present study, the protective effects and molecular mechanism of alliin on Lipopolysaccharides (LPS)-induced acute lung injury (ALI) were analyzed. LPS-induced ALI was induced in BALB/c mice by intranasal instillation of LPS. Alliin was administered intraperitoneally to mice 1 h after LPS treatment. The results showed that alliin markedly inhibited lung myeloperoxidase (MPO) activity and wet/dry (W/D) ratio induced by LPS. Alliin also inhibited TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF) induced by LPS. Furthermore, LPS-induced lung pathological injury was attenuated by treatment of alliin. LPS-induced NF-κB activation was significantly inhibited by alliin. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) was up-regulated by treatment of alliin. Taken together, these results suggested that alliin protected against LPS-induced ALI by activating PPARγ, which subsequently inhibited LPS-induced NF-κB activation and inflammatory response. Alliin might be used as an anti-inflammatory agent in the treatment of ALI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Activation of dimeric glucocorticoid receptors in osteoclast progenitors potentiates RANKL induced mature osteoclast bone resorbing activity.

    Science.gov (United States)

    Conaway, H Herschel; Henning, Petra; Lie, Anita; Tuckermann, Jan; Lerner, Ulf H

    2016-12-01

    Glucocorticoid (GC) therapy is the greatest risk factor for secondary osteoporosis. Pathogenic mechanisms involve an initial increase in bone resorption followed by decreased bone formation. To gain a better understanding of the resorptive activity of GCs, we have used mouse bone marrow macrophages (BMM) to determine if GCs can directly modulate RANKL stimulated osteoclast formation and/or activity. In agreement with previous studies, experiments performed in plastic wells showed that GCs (dexamethasone, hydrocortisone, and prednisolone) inhibited osteoclast number and size during the initial phases of RANKL stimulated osteoclastogenesis; however, in prolonged cultures, decreased apoptosis was observed and escape from GC induced inhibition occurred with an enhanced number of osteoclasts formed, many with an increased area. When BMM cells were seeded on bone slices, GCs robustly enhanced RANKL stimulated formation of resorption pits and release of CTX without affecting the number or size of osteoclasts formed and with no effect on apoptosis. Stimulation of pit formation was not associated with increased life span of osteoclasts or an effect on mRNA expression of several osteoclastic or osteoclastogenic genes. The potentiation of RANKL induced CTX release by dexamethasone was significantly less in BMM cells from mice with conditional knockout of the osteoclastic glucocorticoid receptor and completely absent in cells from GR dim mice, which carry a point mutation in one dimerizing interface of the GC receptor. These data suggest that: 1. Plastic is a poor medium to use for studying direct effects of GCs on osteoclasts 2. GCs can enhance bone resorption without decreasing apoptosis, and 3. A direct enhancement of RANKL mediated resorption is stimulated by the dimeric GC-receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Anticoagulation intensity of rivaroxaban for stroke patients at a special low dosage in Japan.

    Directory of Open Access Journals (Sweden)

    Takuya Okata

    Full Text Available In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30-49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients.Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT, activated partial thromboplastin time (aPTT, and estimated plasma concentration of rivaroxaban (Criv based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach.Of 110 patients (37 women, 75±9 years old, 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate -0.43, 95% CI -0.60 to -0.26 after multivariate-adjustment.The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.

  5. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  6. Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation.

    Science.gov (United States)

    Yang, Xiantao; Zhu, Yuejie; Wang, Chao; Guan, Zhu; Zhang, Lihe; Yang, Zhenjun

    2017-07-01

    Recently, aptamers have been extensively researched for therapy and diagnostic applications. Thrombin-binding aptamer is a 15nt deoxyribonucleic acid screened by SELEX, it can specifically bind to thrombin and inhibit blood coagulation. Since it is also endowed with excellent antitumor activity, the intrinsic anticoagulation advantage converted to a main potential side effect for its further application in antiproliferative therapy. Site-specific alkylation was conducted through nucleophilic reaction of phosphorothioated TBAs using bromide reagents. Circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) measurements were used to evaluate anticoagulation activity, and a CCK-8 assay was used to determine cell proliferation activity. The CD spectra of the modified TBAs were weakened, and their affinity for thrombin was dramatically reduced, as reflected by the K D values. On the other hand, their inhibition of A549 cells was retained. Incorporation of different alkyls apparently disrupted the binding of TBA to thrombin while maintaining the antitumor activity. A new modification strategy was established for the use of TBA as a more selective antitumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    International Nuclear Information System (INIS)

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li; Li, Xiao-Dong; Hong, Mo-Na; Chen, Qi-Zhi; Han, Wei-Qing; Gao, Ping-Jin

    2016-01-01

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  8. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    Energy Technology Data Exchange (ETDEWEB)

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Li, Xiao-Dong [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Hong, Mo-Na [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Chen, Qi-Zhi [Shanghai Institute of Hypertension, Shanghai (China); Han, Wei-Qing, E-mail: whan020@gmail.com [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Gao, Ping-Jin, E-mail: gaopingjin@sibs.ac.cn [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China)

    2016-04-29

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  9. R and D activities on radiation induced mutation breeding

    International Nuclear Information System (INIS)

    Lapade, A.G.; Asencion, A.B.; Santos, I.S.; Grafia, A.O.; Veluz, AM.S.; Barrida, A.C.; Marbella, L.J.

    1996-01-01

    This paper summarizes the accomplishments, prospects and future plans of mutation breeding for crop improvement at the Philippine Nuclear Research Institute (PNRI). Mutation induction has become a proven way creating variation within a crop variety and inducing desired attributes that cannot be found in nature or have been lost during evolution. Several improved varieties with desirable traits were successfully developed through induced mutation breeding at our research institute. In rice, mutation breeding has resulted in the development of new varieties: (1) PARC 2, (2) Milagrosa mutant, (3) Bengawan mutant and (4) Azmil mutant. Mutation breeding in leguminous crops has led to the induction of an improved L 114 soybean mutant that is shorter that the original variety but yield about 40% more. Several PAEC mungbean varieties characterized with long pods that are non-shattering were also induced. In asexually propagated crops, an increase in yield and chlorophyll mutants were obtained in sweet potatos. Likewise, chlorophyll mutant which look-like 'ornamental bromeliads' and a mutant with reduced spines have been developed in pineapple Queen variety. At present, we have started a new project in mutation breeding in ornamentals. Tissue culture is being utilized in our mutation breeding program. In the near future, radiation induced mutagenesis coupled with in vitro culture techniques on protoplast culture and somatic hybridization will be integrated into our mutation breeding program to facilitate the production of new crop varieties. (author)

  10. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for ...

  11. Monitoring the effectiveness of the natural anticoagulant sulodexide in pregnant women with autoimmune hyperthyroidism on the background of hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    A.Yu. Scherbakov

    2017-04-01

    Full Text Available According to modern concepts, the occurrence of complications in utero-placental pool during pregnancy is a common cause of primary placental insufficiency, severe forms of late gestosis, recurrent miscarriage. It is obvious that the study of the nature of violations in the hemostatic system during pregnancy and the development of methods for timely correction will be the prevention of many obstetric diseases. Among the factors that affect hemostasis, thyroid hormones occupy a special place, they are able to influence not only the functional activity of platelets, but also adjust the intensity of the plasma and tissue fibrinolysis. Oppression of fibrinolytic activity is one of the pathogenetic factors of thrombosis development. The aim – to study the efficacy of natural anticoagulant sulodexide in pregnant women with autoimmune hyperthyroidism on the background of hyperhomocysteinemia. Materials and methods. The study involved 34 pregnant women with autoimmune hyperthyroidism complicated by hyperhomocysteinemia. A control group comprised 29 somatically healthy pregnant women. General clinical examination was carried out, the main indicators of all the links of the hemostatic system and the level of homocysteine were determined. Results. We determined that the main group of pregnant is characterized with chronometric and structural hypercoagulation, which manifests itself in the form of subclinical syndrome of disseminated intravascular coagulation, leading to complications of pregnancy, childbirth and the pathological condition of the fetus. Addition of anticoagulant sulodexide to the standard treatment led to the significant change in indices of all the components of hemostasis in pregnant women of the main group, in particular normalization of the total capacity of the coagulation and fibrinolytic systems. Decrease in activity of intravascular coagulation and platelet aggregation, the level of homocysteine was marked. Clinical indicators of

  12. Cerebrovascular Accident due to Thyroid Storm: Should We Anticoagulate?

    Directory of Open Access Journals (Sweden)

    Alex Gonzalez-Bossolo

    2016-01-01

    Full Text Available Thyroid storm is a life-threatening condition that occurs secondary to an uncontrolled hyperthyroid state. Atrial fibrillation is a cardiovascular complication occurring in up to 15% of patients experiencing thyroid storm, and if left untreated this condition could have up to a 25% mortality rate. Thyroid storm with stroke is a rare presentation. This case report details a left middle cerebral artery (MCA stroke with global aphasia and thyroid storm in a 53-year-old Hispanic male patient. Although uncommon, this combination has been reported in multiple case series. Although it is well documented that dysfunctional thyroid levels promote a hypercoagulable state, available guidelines from multiple entities are unclear on whether anticoagulation therapy is appropriate in this situation.

  13. New oral anticoagulants in the prevention of stroke

    Directory of Open Access Journals (Sweden)

    Konrad Jarząbek

    2013-10-01

    Full Text Available Atrial fibrillation is associated with a few folds higher risk of stroke. Traditional vitamin K antagonists used in the prevention of stroke in patients with non-valvular atrial fibrillation are often not efficient enough due to their interactions with a broad range of substances including medicines or food ingridients and problems with monitoring the treatment. New oral anticoagulants pose an alternative for the vitamin K antagonists. They are equally efficient in the prevention of stroke, but are safer and have no requirement for routine coagulation monitoring. We present a case of a patient with atrial fibrillation, high risk of tromboembolism and recurring episodes of hemorrhages. Considering the possible complications, rivaroxaban was administered.

  14. Prosthetic mitral valve thrombosis in pregnancy: from thrombolysis to anticoagulation.

    Science.gov (United States)

    Cardoso, Gonçalo; Aguiar, Carlos; Andrade, Maria João; Patrício, Lino; Freire, Isabel; Serrano, Fátima; Anjos, Rui; Mendes, Miguel

    2015-01-01

    Pregnant women with mechanical prosthetic heart valves are at increased risk for valve thrombosis. Management decisions for this life-threatening complication are complex. Open-heart surgery has a very high risk of maternal mortality and fetal loss. Bleeding and embolic risks associated with thrombolytic agents, the limited efficacy of thrombolysis in certain subgroups, and a lack of experience in the setting of pregnancy raise important concerns. We report a case of mitral prosthetic valve thrombosis in early pregnancy, which was successfully treated with streptokinase. Ten years later, the same patient had an uneventful pregnancy, throughout which acenocoumarol was maintained. With this case we review the prevention (with oral anticoagulant therapy) and treatment of prosthetic valve thrombosis during pregnancy, which is important for both obstetrician and cardiologist. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Role of novel anticoagulants for patients with mechanical heart valves.

    Science.gov (United States)

    Forsberg, Peter; DeSancho, Maria T

    2014-11-01

    The introduction of the target-specific oral anticoagulants (TSOACs) has led to a major shift in the management of patients at risk for thrombosis. The landscape continues to evolve as the evidence regarding their efficacy and safety in various clinical situations emerges. Antithrombotic therapy for thromboprophylaxis in patients with mechanical heart valves is challenging. To date, the RE-ALIGN trial comparing dabigatran etexilate to warfarin is the only randomized controlled study in this patient population. The higher risk of thromboembolic and bleeding events in the group of patients who received dabigatran compared with warfarin reinforced current guidelines recommending against the use of TSOACs in patients with mechanical heart valves. However, additional studies are needed to find suitable alternatives to vitamin K antagonists in this unique patient population.

  16. Ischaemic stroke in patients treated with oral anticoagulants.

    Science.gov (United States)

    Cano, L M; Cardona, P; Quesada, H; Lara, B; Rubio, F

    2016-01-01

    Cardioembolic stroke is associated with poorer outcomes. Prevention is based on oral anticoagulant (OAC) therapy. Haemorrhage is the main complication of OACs, which are sometimes ineffective. We retrospectively reviewed 1014 consecutive patients who suffered an ischaemic stroke between 2011 and 2013, analysing those who were receiving OAC treatment at stroke onset (107 patients in total) with special attention to aetiology, outcomes, and INR value in the acute phase. The mean age (SD) was 71.9 (10) years. Patients had been treated with OACs for 5.9 (5.5) years; 98.1% of them were being treated for heart disease. INR was strokes were cardioembolic and 1.9% were atherothrombotic. Anticoagulation therapy was discontinued in 48 patients (44.9%) due to haemorrhagic transformation (24 patients), extensive infarction (23), or endarterectomy (1). Therapy was resumed in 24 patients (50%) after a mean lapse of 36 days. This was not possible in the remaining patients because of death or severe sequelae. New OACs (NOACs) were prescribed to 9 patients (18.7% of all potential candidates). At 3 months, patients with INR>1.7 in the acute phase exhibited better outcomes than patients with INR≤1.7 (mRS 0-2 in 62% vs 30.8%; death in 10% vs 38.4%; P=.0004). Some patients taking OACs suffer ischaemic strokes that are usually cardioembolic, especially if INR is below the therapeutic range. OACs can be resumed without complications, and NOACs are still underused. Despite cases in which treatment is ineffective, outcomes are better when INR is above 1.7 at stroke onset. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Protease-Activated Receptor-2 Activation Contributes to House Dust Mite-Induced IgE Responses in Mice

    NARCIS (Netherlands)

    Post, Sijranke; Heijink, Irene; Petersen, A H; de Bruin, Harold G.; van Oosterhout, Antoon J. M.; Nawijn, Martijn C.

    2014-01-01

    Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium,

  18. Active Gaming as a Form of Exercise to Induce Hypoalgesia.

    Science.gov (United States)

    Carey, Christopher; Naugle, Keith E; Aqeel, Dania; Ohlman, Thomas; Naugle, Kelly M

    2017-08-01

    An acute bout of moderate-to-vigorous exercise temporarily reduces pain sensitivity in healthy adults. Recently, active gaming has been rising in popularity as a means of light-to-moderate exercise and may be particularly suitable for deconditioned individuals. Whether the physical activity elicited in active games can produce a hypoalgesic effect remains unknown. The purpose of this study was to determine whether active videogames can reduce pressure and heat pain sensitivity in healthy adults. We also evaluated the relationship between the physical activity elicited by the games and the magnitude of the hypoalgesic response. Twenty-one healthy adults played four different active games on separate days, including Microsoft ® Kinect Xbox ® One's Fighter Within and Sports Rival's Tennis, and Nintendo ® Wii™ Sports' Boxing and Tennis. Heat pain thresholds on the forearm and pressure pain thresholds (PPTs) on the trapezius and forearm were assessed immediately before and after a 15-minute active gaming or control session. Minutes spent in sedentary time and moderate-to-vigorous physical activity (MVPA) during active gaming were measured with an accelerometer. The analyses revealed that PPTs at the forearm and trapezius significantly increased from pretest to posttest following Kinect Fighter Within. PPTs at the trapezius also significantly increased from pretest to posttest following Wii Boxing. The magnitude of the hypoalgesic response was significantly correlated with MVPA and sedentary time during gameplay. These results suggest that an active gaming session played at a moderate intensity is capable of temporarily reducing pain sensitivity.

  19. Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues.

    Science.gov (United States)

    Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao

    2017-09-01

    Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl 3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl 3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl 3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl 3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl 3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload.

    Science.gov (United States)

    Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang

    2013-09-01

    To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

  1. BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats.

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    Hiroshi Yukitake

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1, an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO activity were observed in a dextran sulfate sodium (DSS-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties.

  2. The anticoagulant ability of ferulic acid and its applications for improving the blood compatibility of silk fibroin

    Energy Technology Data Exchange (ETDEWEB)

    Wang Song; Gao Zhen; Chen Xiaomeng; Lian Xiaojie; Zhu Hesun [School of Material Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); Zheng Jun; Sun Lizhong [Department of Cardiac Surgery, Cardiovascular Institute and Fu Wai Hospital, CAMS and PUMC, Beijing 100037 (China)], E-mail: wangsongbit@hotmail.com

    2008-12-15

    The hemocompatibility of silk fibroin (SF) was improved with ferulic acid (FA) by graft polymerization. Ferulic acid is an active ingredient of many Chinese herbal medicines, such as Chuanxiong (Rhizoma ligustici wallichii), Danggui (Angelica sinensis) and Awei (Asafoetida giantfennel), which have been used to treat cardiovascular diseases by Chinese physicians for thousands of years. The inhibitory functions of FA on blood coagulation and erythrocyte agglutination were first characterized by a Lee-White test tube method and a micropipette technique, respectively. Then, FA was immobilized on SF by graft polymerization and the surface composition of modified SF was characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR), x-ray photoelectron spectroscopy (XPS) and optical microscopy. The anticoagulant activity of modified SF was assessed, respectively, by in vitro clotting time measurements on a photo-optical clot detection instrument and with the Lee-White test tube method. The test results indicated that in comparison to untreated SF, the anticoagulant activity of modified SF has been improved significantly. Moreover, the SF surface composition is altered by FA but its {beta}-sheet conformation is not disturbed.

  3. Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK signalling

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    Verena Christen

    Full Text Available Humans may be exposed to engineered silica nanoparticles (SiO2-NPs but potential adverse effects are poorly understood, in particular in relation to cellular effects and modes of action. Here we studied effects of SiO2-NPs on cellular function in human hepatoma cells (Huh7. Exposure for 24 h to 10 and 50 μg/ml SiO2-NPs led to induction of endoplasmic reticulum (ER stress as demonstrated by transcriptional induction of DNAJB9, GADD34, CHOP, as well as CHOP target genes BIM, CHAC-1, NOXA and PUMA. In addition, CHOP protein was induced. In addition, SiO2-NPs induced an inflammatory response as demonstrated by induction of TNF-α and IL-8. Activation of MAPK signalling was investigated employing a PCR array upon exposure of Huh7 cells to SiO2-NPs. Five of 84 analysed genes, including P21, P19, CFOS, CJUN and KSR1 exhibited significant transcriptional up-regulation, and 18 genes a significant down-regulation. Strongest down-regulation occurred for the proto-oncogene BRAF, MAPK11, one of the four p38 MAPK genes, and for NFATC4. Strong induction of CFOS, CJUN, FRA1 and CMYC was found after exposure to 50 μg/ml SiO2-NPs for 24 h. To analyse for effects derived from up-regulation of TNF-α, Huh7 cells were exposed to SiO2-NPs in the presence of the TNF-α inhibitor sauchinone, which reduced the induction of the TNF-α transcript by about 50%. These data demonstrate that SiO2-NPs induce ER stress, MAPK pathway and lead to inflammatory reaction in human hepatoma cells. Health implications of SiO2-NPs exposure should further be investigated for a risk assessment of these frequently used nanoparticles. Keywords: Silica nanoparticles, Endoplasmic reticulum stress, MAPK, TNF-α, Huh7 cells

  4. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

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    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  5. Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies.

    Science.gov (United States)

    Galland, Joris; Mohamed, Shirine; Revuz, Sabine; de Maistre, Emmanuel; de Laat, Bas; Marie, Pierre-Yves; Zuily, Stéphane; Lévy, Bruno; Regnault, Véronique; Wahl, Denis

    2016-07-01

    Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins.

  6. Treatment of metabolic alkalosis during continuous renal replacement therapy with regional citrate anticoagulation.

    Science.gov (United States)

    Kindgen-Milles, D; Amman, J; Kleinekofort, W; Morgera, S

    2008-04-01

    The use of citrate as an anticoagulant in continuous renal replacement therapy is an effective method to achieve regional anticoagulation of the extracorporeal blood circuit and to avoid systemic anticoagulation. This allows bleeding complications to be reduced and filter life time to be prolonged. However, citrate enters the systemic circulation and is metabolized in the liver to bicarbonate, causing metabolic alkalosis in some patients. In this case report, we discuss therapeutic interventions to control the acid-base status and to restore normal pH during continuous citrate hemodialysis.

  7. Monitoring the Effects and Antidotes of the Non-vitamin K Oral Anticoagulants

    DEFF Research Database (Denmark)

    Rahmat, Nur A; Lip, Gregory Y H

    2015-01-01

    In the last decade, we have witnessed the emergence of the oral non-vitamin K oral anticoagulants (NOACs), which have numerous advantages compared with the vitamin K antagonists, particularly their lack of need for monitoring; as a result their use is increasing. Nonetheless, the NOACs face two...... major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development....

  8. Anticoagulation and delayed bowel resection in the management of mesenteric venous thrombosis.

    Science.gov (United States)

    Kim, Hyung-Kee; Chun, Jae Min; Huh, Seung

    2013-08-14

    Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and, ultimately, bowel infarction requiring surgical intervention. Systemic anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous thrombosis. However, the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in patients with suspected bowel ischemia. Here we describe a patient with acute mesenteric venous thrombosis who presented with bowel ischemia and was treated with anticoagulation and delayed short-segment bowel resection.

  9. Therapeutic Anticoagulant Does not Modify Thromboses Rate Vein after Venous Reconstruction Following Pancreaticoduodenectomy

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    Mehdi Ouaïssi

    2008-01-01

    confluent SMV (n=12; type III (n=1 resulted from a primary end-to-end anastomosis above confluent and PTFE graph was used for reconstruction for type IV (n=2. Curative anticoagulant treatment was always indicated after type IV (n=2 resection, and after resection of type II when the length of venous resection was longer than ≥2 cm. Results. Venous thrombosis rate reached: 0%, 41%, and 100% for type I, II, IV resections, respectively. Among them four patients received curative anticoagulant treatment. Conclusion. After a portal vein resection was achieved in the course of a PD, curative postoperative anticoagulation does not prevent efficiently the onset of thrombosis.

  10. Will NOACs become the new standard of care in anticoagulation therapy?

    Directory of Open Access Journals (Sweden)

    Ergene Oktay

    2015-06-01

    Full Text Available Atrial fibrillation is the most common cardiac arrhythmia in the general population, with a prevalence of 1–3%, which increases with age, reaching 15% in elderly people. Prophylaxis of ischemic stroke with warfarin was the gold standard of medical management for many years. On the other hand heparin and warfarin was the main pharmacologic agents for the prophylaxis/treatment of venous thromboembolism. In the last 5 years warfarin is getting replaced by non-vitamin K antagonist oral anticoagulants at least partly. In this article it is attempted to foresee whether new oral anticoagulants will become the new standard of care in anticoagulation therapy.

  11. Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension.

    Science.gov (United States)

    Cirulis, Meghan M; Ryan, John J

    2016-05-01

    The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to provide guidance on this controversial topic in the absence of future dedicated investigations.

  12. Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

    Science.gov (United States)

    Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

    2014-04-01

    The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. A mainframe interfacing computer management system for the control of oral anticoagulant therapy.

    Science.gov (United States)

    Yates, P; Stear, M

    1992-01-01

    A unique computerized management system has been used to control the anticoagulation of over 400 patients at a large teaching hospital for the last eighteen months. The system is located on the main pathology computer which can be interfaced with the patient administration system (PAS). This enables files in the anticoagulant program to be linked with files in the PAS and files in the haematology database. This system has many advantages over a stand-alone microcomputer system and will form the basis for the next generation of computerized anticoagulant management systems.

  14. Exercise-induced AMPK activity in skeletal muscle

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Mortensen, Brynjulf; Pehmøller, Christian

    2013-01-01

    The energy/fuel sensor 5'-AMP-activated protein kinase (AMPK) is viewed as a master regulator of cellular energy balance due to its many roles in glucose, lipid, and protein metabolism. In this review we focus on the regulation of AMPK activity in skeletal muscle and its involvement in glucose...

  15. Measurement of neutron-induced activation cross-sections using ...

    Indian Academy of Sciences (India)

    Manish Sharma et al. Table 1. Geometrical details of Co- and Ta-activation detectors used in Gam- ma-2 experiment. Element. 181Ta. 59Co. Cross-sectional area. 2.64 cm2 ... the details of the activated detectors, Au, Bi, and Th as well as the methodology of analysis for the estimation of 'one group cross-section'. Further ...

  16. Extraction and anticoagulant activity of sulfated polysaccharides from Caulerpa cupressoides var. lycopodium (Vahl C. Agardh (Chlorophyceae = Extração e atividade anticoagulante dos polissacarídeos sulfatados da clorofícea Caulerpa cupressoides var. lycopodium (Vahl C. Agardh = Extração e atividade anticoagulante dos polissacarídeos sulfatados da clorofícea Caulerpa cupressoides var. lycopodium (Vahl C. Agardh.

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2011-04-01

    Full Text Available The reportedly low standard quality of heparin (HEP for use in cardiac surgeries has led to concern in the Brazilian and international markets. Sulfated polysaccharides (SPs from seaweeds have been regarded as promising substitutes for HEP. The aim of this study was to sequentially extract total SPs (TSPs from Caulerpa cupressoides (Chlorophyceae with papain in 100 mM sodium acetate buffer (pH 5.0 containing 5 mM cysteine and 5 mM EDTA, followed byfractionation by ion-exchange chromatography (DEAE-cellulose, and then evaluate the anticoagulant potential of SP fractions by activated partial thromboplastin time (APTT using normal human plasma and compare it to standard HEP (193 IU mg-1. The obtained fractions were chemically characterized by chemical composition and agarose gel electrophoresis. The yield was 4.61%, and three fractions of SP (F I, F II and F III eluted with 0.50, 0.75 and 1.00 M of NaCl,respectively, were observed on chromatography profiles; however, differences in charge densities patterns and degree of resolution among them were revealed by electrophoresis. SPs were capable of modifying APTT only in fractions eluted with 0.75 M of NaCl, whose activities were 23.37 and 25.76 IU mg-1, respectively, and the charge density was prerequisite to activity. Therefore, C. cupressoides is a source of SPs possessing low anticoagulant potential compared to HEP.O baixo padrão de qualidade outrora declarado da heparina (HEP para o uso em cirurgias cardíacas tem levado preocupação nos mercados nacional e internacional. Os polissacarídeos sulfatados (PSs de algasmarinhas têm sido considerados como promissores substitutos para HEP. Objetivou-se a extrair sequencialmente PSs totais (PSTs da clorofícea Caulerpa cupressoides com papaína em tampão acetato de sódio 100 mM (pH 5,0 contendo cisteína 5 mM e EDTA 5 mM, fracionar por cromatografia de troca iônica (DEAE-celulose e avaliar o potencial anticoagulante das frações de PS por meio do

  17. A novel AMPK activator hernandezine inhibits LPS-induced TNFα production.

    Science.gov (United States)

    Li, Ping; Li, Xiaofang; Wu, Yonghong; Li, Manxiang; Wang, Xiaochuang

    2017-09-15

    Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS. Remarkably, hernandezine was unable to further inhibit LPS-mediated TNFα production in caAMPKα-expressing cells. Hernandezine inhibited LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NFκB) activation. Treatment of hernandezine in ex-vivo cultured primary human peripheral blood mononuclear cells (PBMCs) also largely attenuated LPS-induced TNFα production. Together, we conclude that AMPK activation by hernandezine inhibits LPS-induced TNFα production in macrophages/monocytes.

  18. Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

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    Wang Ying-Wei

    2010-01-01

    Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

  19. Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia.

    Science.gov (United States)

    Poli, Maura; Asperti, Michela; Ruzzenenti, Paola; Naggi, Annamaria; Arosio, Paolo

    2017-04-08

    The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability. The chemical characteristics for high anti-hepcidin activity in vitro and in vivo include the 2O-and 6O-sulfation and a molecular weight above 7 kDa. The most potent heparins have been found to be the super-sulfated ones, active in hepcidin suppression with a molecular weight as low as 4 kDa. Moreover, the alteration of endogenous heparan sulfates has been found to cause a reduction in hepcidin expression in vitro and in vivo, indicating that heparins act by interfering with the interaction between BMPs and components of the complex involved in the activation of the BMP/SMAD1/5/8 pathway. This review summarizes recent findings on the anti-hepcidin activity of heparins and their possible use for the treatment of anemia caused by hepcidin excess, including the anemia of chronic diseases.

  20. Oxygen plasma modified P(3HB-4HB) used as anticoagulant materials

    Science.gov (United States)

    Zhan, Jiezhao; Tian, Xiaojun; Zhu, Yongjun; Wang, Lin; Ren, Li

    2013-09-01

    In this article, we report the modification of P(3HB-4HB) film with oxygen plasma. The results showed that both the chemical components and topography of the P(3HB-4HB) film changed after oxygen plasma modification. In addition, the decrease of contact angle and the increase of the surface oxygen content were observed. The results of BSA adsorption onto those films studied by QCM-D showed that the plasma treatment could improve the protein-resistant activity of the film. After 10-minute plasma treatment, the BSA-resistant activity of the film improved 27% in PBS buffer solution and 57.5% in aqueous solution. Platelet adhesion test showed that the platelet-resistant activity of the film improved 68.6%, 82.3%, 96.8% after treated for 2, 5 and 10 min, respectively. Also, the cck8 assay of L929 cells showed that there was no cytotoxicity for the sample treated with oxygen plasma. This film has the potential to be used as anticoagulant materials, which required high protein-resistant activity.

  1. Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

    Directory of Open Access Journals (Sweden)

    Edrich T

    2015-02-01

    Full Text Available Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative and Pain Medicine, 3Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, 4Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA Purpose: Dabigatran (D is increasingly used for chronic anticoagulation in place of warfarin (W. These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. Patients and methods: In a retrospective study of patients treated with D, W, or neither drug (N undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. Results: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05 to the initial heparin bolus than Group W (approximately 50%. Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the

  2. Study of antihyperglycaemic activity of medicinal plant extracts in alloxan induced diabetic rats

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    Anoja P Attanayake

    2013-01-01

    C onclusion: The aqueous extract of G. arborea, S. pinnata, K. zeylanica, S. caryophyllatum, S. dulcis, S. alnifolia, L. galanga and C. grandis possess potent acute antihyperglycaemic activity in alloxan