A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Inorganic–organic hybrid materials with zirconium oxoclusters as protective coatings on aluminium alloys

Inorganic–organic hybrid materials are attracting a strong scientific interest mainly for their outstanding inherent mechanical and thermal properties, which can be traced back to the intimate coupling of both inorganic and organic components. By carefully choosing the experimental parameters used for their synthesis, chemically and thermally stable acrylate-based hybrid material embedding the zirconium oxocluster Zr₄O₄(OMc)₁₂, where OMcCH₂C(CH₃)C(O)O, can be deposited as UV-cured films on aluminium alloys.

In particular, the molar ratios between the oxocluster and the monomer, the polymerisation time, the amount of photo-initiator and the deposition conditions, by using an home-made spray-coating equipment, were optimised in order to obtain the best performing layers in terms of transparency and hardness to coat aluminium alloy (AA1050, AA6060 and AA2024) sheets. Furthermore, it was also evaluated whether the hybrid coatings behave as barrier to corrosion.

Several coated samples were prepared and characterised. Environmental scanning electronic microscopy (ESEM) and scratch test were used to investigate the morphology of the films and to evaluate their scratch resistance, respectively. Electrochemical impedance spectroscopy (EIS) was performed in order to evaluate if the coatings actually protect the metallic substrate from corrosion.

In order to measure shear storage modulus (G′) and loss modulus (G″) of the materials used for coatings, bulk samples were also obtained by UV-curing of the precursors solution. Dynamical mechanical thermal analysis (DMTA) was performed in shear mode on cured disks of both the hybrid materials and pristine polymer for comparison. The values of T_g were read off as the temperatures of peak of loss modulus. The length and mass of all the samples were measured before and after the DMTA analysis, so that the shrinkage of the materials in that temperature range was exactly evaluated.     

A multi-agent legal recommender system

Infonorma is a multi-agent system that provides its users with recommendations of legal normative instruments they might be interested in. The Filter agent of Infonorma classifies normative instruments represented as Semantic Web documents into legal branches and performs content-based similarity analysis. This agent, as well as the entire Infonorma system, was modeled under the guidelines of MAAEM, a software development methodology for multi-agent application engineering. This article describes the Infonorma requirements specification, the architectural design solution for those requirements, the detailed design of the Filter agent and the implementation model of Infonorma, according to the guidelines of the MAAEM methodology.     

Evaluation of the synergism between ketorolac and morphine in the treatment of postoperative pain

BACKGROUND: The aim of the study is to determine what concentration of ketorolac and morphine administered together i.v. achieve best synergic effect between NSAID antiinflammatory and opioids analgesic properties. DESIGN: Randomized comparative study was carried out on 180 patients, ASA II-IV, undergoing major general surgery, in an University Clinic. METHODS: Postoperative pain therapy by i.v. PCA: group 1 morphine 0.75 mg.ml + ketorolac 0.75 mg.ml; group 2 morphine 0.50 mg.ml + ketorolac 1.50 mg.ml; group 3 morphine 0.25 mg.ml + ketorolac 1.50 mg.ml; in saline solution. Initial bolus: 2 ml. Continuous infusion 1.5 ml.h. Demand bolus: 0.2 ml. Lockout time: 30 minutes. Evaluations included: pain intensity (T0, T3, T18); total amount of infused drugs (T18); number of valid demands and attempts (T18); amount of autoadministered analgesic drugs in percent of highest available amount (T18); side effects (T18); patient's judgment. DATA ANALYSIS: ANOVA and Student's "t"-test. RESULTS: A statistically significant reduction of pain intensity was found after 3 and 18 hours in the three groups, no differences were found among the groups. Group 2 required an amount of autoadministered drugs significantly lower than other groups. Rare side effects. Patient's judgment was generally positive. CONCLUSIONS: Results suggest a greater synergetic effect between morphine and ketorolac in concentrations used in group 2.     

Multielement and automated radiochemical separation procedures for activation analysis

In recent years the demand for information about the distribution of elements at trace concentration levels in high purity materials and in biological, environmental and geological specimens has increased greatly. Neutron activation analysis can play an important role in obtaining the required information. Radiochemical separations are required in many of the applications mentioned. A critical review of the progress made over the last 15 years in the development and application of radiochemical separation schemes for multielement activation analysis and in their automation is presented. About 80 radiochemical separation schemes are reviewed. Advantages and disadvantages of the automation of radiochemical separations are critically analysed. The various machines developed are illustrated and technical suggestions for the development of automated machines are given.     

Variations of iridoid oleuropein in Italian olive varieties during growth and maturation

This research paper reports on the concentrations of oleuropein in fruits of seven Italian olive cultivars. These oleuropein levels, during fruit growth and maturation, were monitored by taking olive samples from the same olive trees grown in Middle Italy. A novel high‐resolution gas chromatography (HRGC) oleuropein quantification method and a new high‐performance liquid chromatography (HPLC) method were developed. The olive fruits showed high contents of oleuropein, which were greatly influenced by the olive cultivar (genetic store) factor. The stage of fruit growth and maturation was another factor strongly affecting the contents of iridoid oleuropein in olive drupes, whatever the olive cultivar considered. Green olives had much higher concentrations of this biofunctional glucoside, which decreased regularly during fruit growth and ripeness. No differences were observed between the two developed oleuropein quantification methods, which gave, for all the olive cultivars, average values of fruit oleuropein contents that were not statistically different. These two reliable repetitive methods, noticeably the HPLC one (which also showed a lower running time), could be used for routine determination of oleuropein in olive drupes. We observed that, in general, olive cultivars having high oleuropein concentrations in the fruits were also characterized by marked oleuropein contents in the leaves.     

Structure-related behavior of hybrid organic–inorganic materials prepared in different synthesis conditions from Zr-based NBBs and 3-methacryloxypropyl trimethoxysilane

The copolymerization of zirconium oxo-clusters (Zr12) with 3-methacryloxypropyl (trimethoxy)silane (MPTMS), using a Si/Zr molar ratio of 4, was investigated. The hybrid samples were prepared both with and without organosilane prehydrolysis. Differential scanning calorimetry (DSC), multinuclear liquid, and solid state NMR analyses and Fourier transform infrared (FTIR) spectroscopy were used to characterize the hybrid materials and study the influence of synthesis conditions on condensation and polymerization. The degree of condensation (DOC) of the silsesquioxane network and the polymerization yield are generally high. However, the organosilane prehydrolysis step leads to the reduction of the extent of phase interaction, thus favoring the phase separation between silica-zirconia-based domains. Dynamic mechanical spectroscopy (DMS) analyses were performed on the hybrid polymers obtained by means of the two synthetic pathways. The sample prepared without the organosilane prehydrolysis step presents a higher glass transition temperature (T_g) than the one with silane prehydrolysis. By heating above the T_g, the samples retain shape and size, due to the lack of viscous flow. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012