Navegando por Palavras-chave "Hemorrhagic activity"

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    Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp
    (Elsevier B.V., 2008-11-01) Brito, Adriana S.; Arimateia, Dayse S.; Souza, Lucilla R.; Lima, Marcelo A.; Santos, Vanessa O.; Medeiros, Valquiria P. [UNIFESP]; Ferreira, Paula A.; Silva, Rodrigo A.; Ferreira, Carmen V.; Justo, Giselle Z. [UNIFESP]; Leite, Edda L.; Andrade, Giulianna P. V.; Oliveira, Fernanda W.; Nader, Helena B. [UNIFESP]; Chavante, Suely F.; Univ Fed Rio Grande do Norte; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)
    The anti-inflammatory properties of a heparin-like compound from the shrimp Litopenaeus vannamei are related. Besides reducing significantly (p < 0.001) the influx of inflammatory cells to injury site in a model of acute inflammation, shrimp heparin-like compound was able to reduce the matrix metalloproteinase (MMPs) activity in the peritoneal lavage of inflamed animals. Moreover, this compound also reduced almost 90% the activity of MMP-9 secreted by human activated leukocytes. Negligible anti-coagulant activities in aPPT assay and a poor bleeding potential make this compound a better alternative than mammalian heparin as a possible anti-inflammatory drug. (C) 2008 Elsevier B.V. All rights reserved.
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    Glycosaminoglycan backbone is not required for the modulation of hemostasis: Effect of different heparin derivatives and non-glycosaminoglycan analogs
    (Elsevier B.V., 2012-06-01) Boucas, Rodrigo I.; Jarrouge-Boucas, Thais R.; Lima, Marcelo A.; Trindade, Edvaldo S.; Moraes, Fabio A.; Cavalheiro, Renan P.; Tersariol, Ivarne L. S.; Hoppenstead, Debra; Fareed, Jawed; Nader, Helena B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Parana; Univ Mogi das Cruzes; Loyola Med Sch
    Heparin and its derivatives are known to regulate a variety of pathophysiological events related to vascular biology. in the present manuscript we examine a variety of heparinomimetics biochemically (electrophoretic behavior and enzymatic degradation) and pharmacologically (in vitro anticoagulant activity and in vivo hemorrhagic and antithrombotic tests) as well as their interactions with cells from the vessel wall using a time resolved fluorometric method and confocal microscopy. Data were determined for unfractionated heparin (UFH), enoxaparin, synthetic heparin pentasaccharide. C3 heparin derived oligosaccharides and phosphosulfomannan (PI-88). While being structurally distinct from UFH, all compounds exhibited anticoagulant, antithrombotic and hemorrhagic activities. in addition, besides the pentasaccharide, they all stimulated the synthesis of an antithrombotic heparan sulfate present at the cell surface and secreted by endothelial cells. Also, like UFH, they interacted with both endothelial and smooth muscle cells and dislodged UFH from its binding sites in a dose dependent manner but, with distinct saturable curves showing that the binding of polymeric structures to extracellular matrix (ECM) proteins does not depend on a glycosaminoglycan backbone. the data also suggest a common pathway, which does not depend on the presence of the conventionally accepted antithrombin binding pentasaccharide, for ECM dependent activity of the heparinomimetic stimulated synthesis of antithrombotic heparan sulfate. Notably, although of similar molecular weight as well as polymeric backbone, the synthetic heparin pentasaccharide showed significant hemorrhagic action and negligible antithrombotic activity in a venous thrombosis model, contrasting with C3, that displayed negligible hemorrhagic effect and potent antithrombotic action. These results provide evidence that structurally unrelated polymers can elicit similar hemostatic activities and show that polymeric sequence is not always crucial for certain activities. the results also suggest that non-GAG structures may provide an alternative route for the pharmaceutical control of hemostasis. (C) 2012 Elsevier B.V. All rights reserved.
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    A non-hemorrhagic hybrid heparin/heparan sulfate with anticoagulant potential
    (Elsevier B.V., 2014-01-02) Brito, Adriana S.; Cavalcante, Romulo S.; Palhares, Lais C. G. F.; Hughes, Ashley J.; Andrade, Giulianna P. V.; Yates, Edwin Alexander [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Lima, Marcelo Andrade de [UNIFESP]; Chavante, Suely F.; Univ Fed Rio Grande do Norte; Univ Liverpool; Diamond Light Source Ltd; Universidade Federal de São Paulo (UNIFESP)
    The structural characterization and the anticoagulant potential of a novel heparin/heparan sulfate-like compound from the heads of Litopenaeus vannamei shrimp are described. While it is distinct from either heparin or heparan sulfate, enzymatic depolymerization and nuclear magnetic resonance spectroscopy analyses revealed that this molecule does share some structural features with heparin, such as the high degree of N- and 6-0-sulfation and minor N-acetylation, and with heparan sulfate, in the glucuronic acid content. Its ability to stabilize human antithrombin explains its significant anticoagulant activity in aPTT and Factor-Xa inhibition assays. Interestingly, in contrast to mammalian heparin, the shrimp compound displayed negligible hemorrhagic effect. Together, these findings have particular interest since they reveal a novel molecule with significant anti-Xa activity coupled with low bleeding effects which make the shrimp heparin/HS-like compound a potential alternative for mammalian heparin. (C) 2013 Elsevier B.V. All rights reserved.