The green algae of the genus Codium have recently been demonstrated to be an important source of sulfated galactans from the marine environment. Here, a sulfated galactan was isolated from the ...species Codium isthmocladum and its structure was studied by a combination of chemical analyses and NMR spectroscopy. Two fractions (SG 1, ∼14 kDa, and SG 2, ∼20 kDa) were derived from this highly polydisperse and heterogeneous polysaccharide. Both exhibited similar structures in 1H 1D NMR spectra. The structural features of SG 2 and its desulfated derivative were analyzed by COSY, TOCSY, DEPT-HSQC, HSQC, and HMBC. This sulfated galactan is composed preponderantly of 4-sulfated, 3-linked β-d-galactopyranosyl units. In minor amounts, it is sulfated and glycosylated at C-6. Pyruvate groups are also found, forming five-membered cyclic ketals as 3,4-O-(1'carboxy)-ethylidene-β-d-galactose residues. A comparison of sulfated galactans from different marine taxonomic groups revealed similar backbones of 3-β-d-Galp-1.
Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular ...weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weights were determined and preparations studied by nuclear magnetic resonance spectroscopy, scanning ultraviolet spectroscopy, circular dichroism and gel permeation chromatography. In general, ULMWHs presented higher 3-O-sulphated glucosamine and unsaturated uronic acid residues, the latter being comparable with their higher degree of depolymerisation. The analysis showed that ULMWHs are structurally related to LMWHs; however, their monosaccharide/oligosaccharide compositions and average molecular weights differed considerably explaining their different anticoagulant activities. The results relate structural features to activity, assisting the development of new and improved therapeutic agents, based on depolymerised heparin, for the prophylaxis and treatment of thrombotic disorders.
Previous reports have shown that heparin may promote human hypotension and vascular relaxation by elevation of NO levels through unclear mechanisms. We hypothesized that endothelial muscarinic M3 ...receptor activation mediates the heparin-induced vasodilation of rat aortic rings. The experiments were carried out using unfractionated heparin extracted from bovine intestinal mucosa, which elicited an endothelium and NO-dependent relaxation of aortic segments with maximal potency and efficacy (EC50100±10 μmol/L; Emax41±3%). Atropine and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide inhibitors reduced the heparin-dependent relaxation, indicating that M3 muscarinic receptor is involved in this phenomenon. However, no direct binding of heparin to muscarinic receptors was observed. More importantly, studies performed using the arginine-glycine-aspartic acid peptide and 1-(1,1-dimethylethyl)-3-(1-naphthalenyl)-1H-pyrazolo3,4-daypyrimidin-4-amine, an Src family inhibitor, reduced by 51% and 73% the heparin-dependent relaxation, respectively, suggesting the coupling of heparin and M3 receptor through extracellular matrix molecules and integrin. Furthermore, unfractionated heparin induced activation of focal adhesion protein kinase, Src, and paxillin. Finally, fluorescence resonance energy transfer approach confirmed the interaction of the M3 receptor to integrin. Taken together, these data demonstrate the participation of M3 receptor and integrin in heparin-dependent relaxation of vascular smooth muscle. These results provide new insights into the molecular mechanism and potential pharmacological action of heparin in vascular physiology.
Proteoglycans encompass a heterogeneous group of glycoconjugates where proteins are substituted with linear, highly negatively charged glycosaminoglycan chains. Sulphated glycosaminoglycans are ...ubiquitous to the animal kingdom of the Eukarya domain. Information on the distribution and characterisation of proteoglycans in invertebrate tissues is limited and restricted to a few species. By the use of multidimensional protein identification technology and immunohistochemistry, this study shows for the first time the presence and tissue localisation of different proteoglycans, such as perlecan, aggrecan, and heparan sulphate proteoglycan, amongst others, in organs of the gastropoda Achatina fulica. Through a proteomic analysis of Golgi proteins and immunohistochemistry of tissue sections, we detected the machinery involved in glycosaminoglycan biosynthesis, related to polymer formation (polymerases), as well as secondary modifications (sulphation and uronic acid epimerization). Therefore, this work not only identifies both the proteoglycan core proteins and glycosaminoglycan biosynthetic enzymes in invertebrates but also provides a novel method for the study of glycosaminoglycan and proteoglycan evolution.
► Different proteoglycans in organs of the gastropoda Achatina fulica. ► Strong relationship between invertebrate and vertebrate proteoglycans. ► Novel technique of Golgi proteomics revealed conserved GAG biosynthetic machinery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since ...been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Generic active pharmaceutical ingredients (APIs) have been commonly used in Brazil, since 1999, but most of them are synthetic and small molecules. Recently, a large number of generic enoxaparins ...were introduced into the market raising concerns related to product-to-product interchangeability, efficiency, and drug counterfeiting. These drugs are produced from biological sources and their production involves complex procedures and purification processes. The present article evaluates several generic enoxaparins, structurally and pharmacologically, and compares them with the branded products. Structural analysis showed that the generic products are, indeed, quite similar to the branded products, however, this similarity cannot be extended to their pharmacological activities. The results showed that generic products must go through extensive structural, pharmacological, and clinical evaluation in order to assess their quality, efficacy and, ultimately, avoid drug counterfeiting before clinical use. Variation was also observed between the branded products, showing that such drugs must be at constant surveillance.
We investigate the effect of superconducting and excitonic interactions, as well as their competition, on Dirac electrons on a bipartite planar lattice. It is shown that, at half-filling, Cooper ...pairs and excitons coexist if the superconducting and excitonic coupling parameters are equal and above a threshold corresponding to a quantum critical point. In the case where only the excitonic interaction is present, we obtain a critical chemical potential, as a function of the interaction strength. Conversely, if only the superconducting interaction is considered, we show that the superconducting gap displays a characteristic dome as charge carriers are doped into the system. We also show that, as the chemical potential increases, superconductivity tends to suppress the excitonic order parameter.
► Dirac fermions on a planar lattice with superconducting and excitonic interactions. ► Half-filling: Cooper pairs and excitons coexist if the interactions are equal. ► For excitonic interaction strength only: A critical chemical potential is obtained. ► For superconducting interaction strength only: The gap displays a dome-shaped curve. ► Both interactions: Superconductivity tends to suppress the excitons at doping.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Various branded low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thrombotic for over 20 years. With the introduction of generic LMWHs and the recent events ...involving heparin contamination, a great deal of effort is being expended in investigating ways of monitoring and regulating this class of complex drugs. In this paper, we present the characterization of different forms of LMWHs, as well as the comparison of 5 enoxaparin copies from different manufactures. The data suggests that, while some of these drugs are structurally comparable, specific analytical methods as well as biological and pharmacological tests may be used to address their similarity, quality and potential interchangeability. The proposed approach may also be useful in comparing biosimilar and branded LMWHs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This systematic review and meta-analysis aims to compare surgical and endoscopic treatment for pancreatic pseudocyst (PP).
The researchers did a search in Medline, EMBASE, Scielo/Lilacs, and Cochrane ...electronic databases for studies comparing surgical and endoscopic drainage of PP s in adult patients. Then, the extracted data were used to perform a meta-analysis. The outcomes were therapeutic success, drainage-related adverse events, general adverse events, recurrence rate, cost, and time of hospitalization.
There was no significant difference between treatment success rate (risk difference RD -0.09; 95% confidence interval CI 0.20,0.01; P = .07), drainage-related adverse events (RD -0.02; 95% CI -0.04,0.08; P = .48), general adverse events (RD -0.05; 95% CI -0.12, 0.02; P = .13) and recurrence (RD: 0.02; 95% CI -0.04,0.07; P = .58) between surgical and endoscopic treatment.Regarding time of hospitalization, the endoscopic group had better results (RD: -4.23; 95% CI -5.18, -3.29; P < .00001). When it comes to treatment cost, the endoscopic arm also had better outcomes (RD: -4.68; 95% CI -5.43,-3.94; P < .00001).
There is no significant difference between surgical and endoscopic treatment success rates, adverse events and recurrence for PP. However, time of hospitalization and treatment costs were lower in the endoscopic group.
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