Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory activity

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.

ANALYSIS OF IN VITRO AND IN VIVO ANTIOXIDANT PROPERTIES OF HYDROPHILIC FRACTIONS FROM THE SEAWEED HALIMEDA MONILE L.

In this work, in vitro and in vivo antioxidant properties of the marine algae Halimeda monile were assessed and the levels of some of its compounds likely to be responsible for such properties were determined. The estimated contents of total polyphenols, chlorophylls a and b and carotenoids were 179.5, 356.3, 452.8 and 42.2 mu g/g dry weight seaweed, respectively. The presence of terpenoids and flavonoids was also observed. The antioxidant activity of two polar fractions from H. monile (lyophilized aqueous extract and free phenolic acid fraction) was evaluated using three antioxidant assays: ferric reducing antioxidant power, 1,1-diphenyl-2-picrylhydrazyl and lipid peroxidation. Treatment of CCl4-induced liver damage in rats with extracts resulted in lower serum thiobarbituric acid-reactive substances levels and higher hepatic glutathione concentrations compared to those observed in the CCl4-treated group. Also, a significant increase in catalase activity was detected after treatment with the extracts. These results suggest that the seaweed H. monile could be a potential source for natural antioxidants.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study

Background: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. Methods: Twenty-eight patients (51 eyes) with long-standing (>= 6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. Results: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). Conclusion: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.