103,101 research outputs found

    LMW-heparins (5 KD) and Oligo-heparins (2 KD) produced by gel-permeation enrichment or radical process: comparison of structures, physico-chemical and biological properties.

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    A process of chemical depolymerization of heparin initiated by free radicals has been developed. The process follows reaction kinetics of apparent first order, and it is possible to obtain heparins with different molecular weights. Low and very low molecular weight heparins (LMWHs, approximately 5 kDa, and Oligo-H, approximately 2 kDa) have been prepared by enriching fractions derived from natural heparin by gel permeation. The LMWHs produced by a radical reaction have been characterized by their physicochemical properties, patterns of constitutive disaccharides, NMR spectra, and biological activities in comparison with those of the LMWHs produced by an enrichment process. The process of free radical degradation is shown to produce heparins with a desired molecular weight (from 1 to greater than 10 kDa) without changes in their primary structure and in their physicochemical properties and with the in vitro biological activities expected for LMWHs. Furthermore, the limits of enzymatic cleavage of heparins with different molecular weights by heparinases and the possibility of obtaining a precise pattern of constitutive disaccharides are discussed

    Water level forecasting through fuzzy logic and artificial neural network approaches

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    In this study three data-driven water level forecasting models are presented and discussed. One is based on the artificial neural networks approach, while the other two are based on the Mamdani and the Takagi-Sugeno fuzzy logic approaches, respectively. All of them are parameterised with reference to flood events alone, where water levels are higher than a selected threshold. The analysis of the three models is performed by using the same input and output variables. However, in order to evaluate their capability to deal with different levels of information, two different input sets are considered. The former is characterized by significant spatial and time aggregated rainfall information, while the latter considers rainfall information more distributed in space and time. The analysis is made with great attention to the reliability and accuracy of each model, with reference to the Reno river at Casalecchio di Reno (Bologna, Italy). It is shown that the two models based on the fuzzy logic approaches perform better when the physical phenomena considered are synthesised by both a limited number of variables and IF-THEN logic statements, while the ANN approach increases its performance when more detailed information is used. As regards the reliability aspect, it is shown that the models based on the fuzzy logic approaches may fail unexpectedly to forecast the water levels, in the sense that in the testing phase, some input combinations are not recognised by the rule system and thus no forecasting is performed. This problem does not occur in the ANN approach

    Analytical techniques for studying structures of dermatan sulfate and low molecular weight dermatan sulfate

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    A process of chemical depolymerization of dermatan sulfate (DS) byfree radicals ispresented. The low molecular weight dermatan sulfate (LMW-DS) obtained by radicai fragmentation is characterized by physico-chemicalproperties (molecular weight, sulfate/carboxyl ratto, uronic acid percentage, electrophoretic profile), purity (by thè agarose electrophoretic method) and structure (specific enzymatic cleavage and "C-NMR). Physico-chemical properties and structure of LMW-DS are compared with those of thè parent DS

    Metodi di analisi integrati applicati alle cinetiche di reazione di polisaccaridi

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    Metodi di analisi integrati applicati alle cinetiche di reazione di polisaccaridi

    Different pharmacokinetics, antithrombotic activity and bleeding effects of heparin and two new fragments administered in rat by subcutaneous route

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    Native heparin (CAS 9005-49-6) and its two new fragments, low molecular weight heparin (LMW-H, 5 kDa) and oligo-heparin (oligo-H, 2 kDa) obtained by radical degradation were characterized as to their physicochemical properties. Heparin fragments differ from unfractionated heparin only in molecular weight. The pharmacokinetics and some pharmacological effects, bleeding and antithrombotic activity, of the three different molecular weight heparins were investigated. The plasma concentrations were determined by an amidolytic method which measures inhibiting effect on factor Xa. The blood levels of each substance were derived from their in vitro calibration curves. The examination of the pharmacokinetics parameters allowed to evaluate the differences in the bioavailability, absorption rate and elimination mechanisms between the three different heparins. The bioavailability, the absorption rate and the distribution of the molecules of heparins in biological compartments depend on the molecular weight. LMW-H and oligo-H exhibit greater antithrombotic activity than unfractionated heparin when administered subcutaneously. The pharmacokinetic behaviour of oligo-H considerably differs from that of unfractionated heparin and LMW-H. This new drug is able to bind cells and plasma proteins differently from heparin and LMW-H. The capacity of oligo-H to bind smooth muscle cells and to interact with myosin is discussed in relation to the bleeding effect
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