Navegando por Palavras-chave "HEPARIN"
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- ItemSomente MetadadadosChemical reduction of carboxyl groups in heparin abolishes its vasodilatory activity(Wiley-Blackwell, 2012-04-01) Paredes-Gamero, Edgar J. [UNIFESP]; Medeiros, Valquiria P. [UNIFESP]; Lima, Marcelo A. [UNIFESP]; Accardo, Camila de Melo [UNIFESP]; Farias, Eduardo H. C. [UNIFESP]; Sassaki, Guilherme I.; Campana, Patricia T.; Miranda, Antonio [UNIFESP]; Ferreira, Alice T. [UNIFESP]; Tersariol, Ivarne L. S. [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Parana; Universidade de São Paulo (USP)Previous studies have shown that heparin induces vascular relaxation via integrin-dependent nitric oxide (NO)-mediated activation of the muscarinic receptor. the aim of this study was to identify the structural features of heparin that are necessary for the induction of vasodilatation. To address this issue, we tested heparin from various sources for their vasodilatation activities in the rat aorta ring. Structural and chemical characteristics of heparin, such as its molecular weight and substitution pattern, did not show a direct correlation with the vasodilation activity. Principal component analysis (PCA) of circular dichroism (CD), 1H-nuclear magnetic resonance (NMR) and vasodilation activity measurements confirmed that there is no direct relationship between the physico-chemical nature and vasodilation activity of the tested heparin samples. To further understand these observations, unfractionated heparin (UFH) from bovine intestinal mucosa, which showed the highest relaxation effect, was chemically modified. Interestingly, non-specific O- and N-desulfation of heparin reduced its anticoagulant, antithrombotic, and antihemostatic activities, but had no effect on its ability to induce vasodilation. On the other hand, chemical reduction of the carboxyl groups abolished heparin-induced vasodilation and reduced the affinity of heparin toward the extracellular matrix (ECM). in addition, dextran and dextran sulfate (linear non-sulfated and highly sulfated polysaccharides, respectively) did not induce significant relaxation, showing that the vasodilation activity of polysaccharides is neither charge-dependent nor backbone unspecific. Our results suggest that desulfated heparin molecules may be used as vasoactive agents due to their low side effects. J. Cell. Biochem. 113: 13591367, 2012. (c) 2011 Wiley Periodicals, Inc.
- ItemSomente MetadadadosEFFECT of DIFFERENT GLYCOSAMINOGLYCANS in A GUINEA-PIG CAROTID-ARTERY THROMBOSIS MODEL(Elsevier B.V., 1994-09-15) Mattar, L.; Maffei, FHA; Nader, H. B.; Dietrich, C. P.; Curi, P. R.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Heparin is the most frequently used drug for the prevention and treatment of thrombosis. Its use, however, is restricted by its side-effects. To study the efficacy of other glycosaminoglycans that could substitute heparin in the management of arterial thrombosis, 60 guinea-pigs were randomly allocated into 6 groups: G1= control, G2= heparin (150 IU/kg), G3= heparan sulfate from beef pancreas (2.5 mg/kg), G4= heparan sulfate from beef lung (2.5 mg/kg), G5= N-acetylated heparan from beef pancreas, G6= dermatan sulfate from beef intestine (2.5 mg/kg). Ten minutes after intravenous injection of the drugs, thrombosis was induced by the injection of a 50% glucose solution into a segment of the right carotid artery isolated between 2 thread loops during 10 minutes. Three hours later the artery was re-exposed and if a thrombus was present it was measured, withdrawn and weighed. Thrombin time and activated partial thromboplastin time were measured in all animals. Thrombus developed in 90% of the animals in the control group, 0% in G2 and G3, 62.5% in G4, 87.5% in G5 and G6. Only in the animals treated with heparin the coagulation tests were prolonged. in conclusion, in the used dose only the heparan sulfate from beef pancreas presented an antithrombotic effect similar to heparin in this experimental model.
- ItemSomente MetadadadosMITOGENIC ACTIVITY of ACIDIC FIBROBLAST GROWTH-FACTOR IS ENHANCED BY HIGHLY SULFATED OLIGOSACCHARIDES DERIVED FROM HEPARIN and HEPARAN-SULFATE(Kluwer Academic Publ, 1993-07-21) Gambarini, A. G.; Miyamoto, C. A.; Lima, G. A.; Nader, H. B.; Dietrich, C. P.; Universidade Federal de São Paulo (UNIFESP)The mitogenic activity of acidic fibroblast growth factor (aFGF) is potentiated by the highly sulfated hexasaccharide [IdoUA,2S-GlcNS,6S]2-[GlcUA-GlcNS,6S] the structural repetitive unit of lung heparin chains. On a mass basis, the effect of both heparin and oligosaccharide are equivalent whereas on a molar basis, heparin, which contains about seven hexasaccharide repeats, is more efficient. On the other hand, a pentasulfated tetrasaccharide or di- and tri-sulfated disaccharides are much less effective in potentiating aFGF activity than the hexasaccharide. If the growth factor is pre-incubated with the hexasaccharide at pH 7.2 and then exposed to pH 3.5 the 306/345 nm fluorescence ratio is similar to that of native aFGF indicating that the oligosaccharide stabilizes a native conformation of the protein. Heparan sulfates extracted from various mammalian tissues were also able to potentiate aFGF mitogenic activity. On a mass basis they were in general less efficient than heparin; however, heparan sulfate prepared from medium conditioned by 3T3 fibroblasts is more efficient than heparin both on a mass and molar basis. A highly sulfated oligosaccharide isolated after digestion of pancreas heparan sulfate with heparitinase I is more active than the intact molecule, reaching a potentiating effect equivalent to that of lung heparin, whereas an N-acetylated oligosaccharide isolated after nitrous acid degradation is inactive. These data suggest that the mitogenic activity of aFGF is primarily potentiated by interacting with highly sulfated regions of heparan sulfates chains.