Development and validation of a HPAE-PAD method for the quantification of CGP69669A, a sialyl Lewis(x) mimetic, in skin permeation studies

A simple, rapid, precise and specific isocratic HPAE‐PAD method for quantification of CGP69669A was developed and validated. CGP69669A is a glycomimetic of sialyl Lewis^x and an antagonist of E‐selectin with potential application in the treatment of inflammatory skin disease. Quantification was performed using a Dionex CarboPac^TM PA‐200 anion‐exchange column (3 × 250 mm) with 100 mm NaOH solution as mobile phase, a flow rate of 0.50 mL/min and an injection volume of 10 μL. A quadruple potential waveform was used to detect the carbohydrate (+0.1 V from 0.00 to 0.40 s, ?2.0 V from 0.41 to 0.42 s, +0.6 V at 0.43 s and ?0.1 V from 0.44 to 0.50 s with current integrated between 0.20 and 0.40 s for detection) and rafinose was employed as an internal standard. The optimized conditions enabled rapid elution of CGP69669A (at 3.0 min) without interference from solvent peaks or substances present in the skin. The method showed good intra‐ and inter‐day precision and accuracy and the response was linear from 1.0 to 25 µg/mL. This is the first validated direct method for the quantification of CGP69669A. It will now be employed in studies investigating the topical and transdermal delivery of CGP69669A in vitro and in vivo and it should also be of use for other applications of this molecule. Copyright © 2011 John Wiley & Sons, Ltd.     

Glycosynthases as tools for the production of glycan analogs of natural products

Oligo-, polysaccharides, and glycoconjugates are a relevant part of the bioactive components of the natural products exploited in therapeutics, diagnostics, food additives, and biomaterials. Glycans are directly involved in important biological processes, such as immunostimulation, anti-inflammatory, antioxidant, and chemoprotectant actions and/or are crucial for their activity, by modulating target recognition, stability, and pharmacokinetics. On the other hand, carbohydrate extracts used for functional studies are rather heterogeneous and lack structural information because of their intrinsic complexity hampering purification and characterization. Therefore, methods for glycoside synthesis and modification are urgently needed. Recently, glycosynthases, engineered glycoside hydrolases with no hydrolytic activity that synthesize glycans in quantitative yields, were introduced. Here we will illustrate how the glycosynthases described so far might be exploited for the production of glycan analogs of natural products and their enormous potential in this field.     

Quality control and analytical test method for Taxus baccata tincture preparation

The homeopathic tincture of Taxus baccata L. is monographed in the current German Homeopathic Pharmacopoeia (HAB 2009). However, the described identification test is a common comparative TLC procedure that might be updated. The purpose of the current work was the quali-quantitative analysis by HPLC/DAD/MS of Taxus tincture. In this study we characterized polyphenolic compounds, in particular four hydroxycinnamic derivatives (0.85 mg/mL) and four flavonoids (quercetin and kaempferol 3-O-rutinoside and xylosyl glucosides); the total polyphenol content was 1.265 mg/mL of tincture. Starting from the official German Homeopathic Pharmacopoeia method of preparation, the aim of this work was to optimize a rapid and reproducible method for the analysis of herbal drugs and tincture, directly prepared in store or the herbalist's shop, to ensure safety and efficacy of the preparation. The procedure has to ensure validation, robustness of the results, and provide a quick response about the composition of compounds in the herbal drug preparation.     

Polyaniline nanofiber–silica composite aerogels

Strong, electrically conducting aerogels were prepared by introducing polyaniline nanofibers to a silica sol just prior to gelation and drying through supercritical carbon dioxide processing. The addition of a few milligrams of polyaniline per cm³ increased the flexural strength of the cylindrical monoliths by 200%. Using preformed polymeric nanofibers avoided filling of microporosity often observed with polymer reinforcement of aerogels and allowed preparation of polyaniline–silica composite aerogels with surface areas over 900 m²/g. Despite the small amount of polyaniline nanofibers (1.3–16.5 wt.%), the composite aerogels were electrically conducting (8.0 × 10^? 8–1.83 × 10^? 5 S/cm) and it was possible to prepare chemiresistor sensors for detection of acidic (HCl) and basic (ammonia) gaseous molecules with response times similar to thin film sensors containing orders of magnitude more polyaniline.     

Thermal and electrical properties of Tri Glycine Sulpho Phosphate (TGSP) and L‐Asparagine doped TGSP crystals

Tri Glycinsulphate with partial substitution of phosphoric acid, namely Tri Glycine Sulpho Phosphate (TGSP) has been grown by slow cooling method. Habit modifications have been observed with change in the concentration of ortho phosphoric acid (H₃PO₄). Monoclinic structure of the grown crystals has been confirmed using X‐ray diffraction analysis. TGSP crystals doped with L – Asparagine were also grown. The doping effect is qualitatively estimated using FTIR analysis. TGA, DTA studies and dielectric measurements were carried out for pure and L‐Asparagine doped TGSP crystals to investigate the thermal and electrical properties of the crystals. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Surface Functionalization of Face Masks with Cold Plasma and Its Effect in Anchoring Polyphenols Extracted from Agri-Food

To improve the capability of non-woven polypropylene-based fabric (NWF-PP) used for face mask production to retain active biomolecules such as polyphenols, the surface functionalization of NWF-PP–directly cut from face masks–was carried out by employing cold plasma with oxygen. The nature/structure of the functional groups, as well as the degree of functionalization, were evaluated by ATR-FTIR and XPS by varying the experimental conditions (generator power, treatment time, and oxygen flow). The effects of plasma activation on mechanical and morphological characteristics were evaluated by stress–strain measurements and SEM analysis. The ability of functionalized NWF-PP to firmly anchor polyphenols extracted from cloves was estimated by ATR-FTIR analysis, IR imaging, extractions in physiological solution, and OIT analysis (before and after extraction), as well as by SEM analysis. All the results obtained converge in showing that, although the plasma treatment causes changes–not only on the surface–with certain detriment to the mechanical performance of the NWF-PP, the incorporated functionalities are able to retain/anchor the active molecules extracted from the cloves, thus stabilizing the treated surfaces against thermo-oxidation even after prolonged extraction.     

Synthesis,Docking Studies and Pharmacological Evaluation of Serotoninergic Ligands Containing a 5-Norbornene-2-Carboxamide Nucleus

A new series of 5-norbornene-2-carboxamide derivatives was prepared and their affinities to the 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors were evaluated and compared to a previously synthesized series of derivatives characterized by exo-N-hydroxy-5-norbornene-2,3-dicarboximidenucleus, in order to identify selective ligands for the above-mentioned subtype receptors. Arylpiperazines represents one of the most important classes of 5-HT_1AR ligands, and recent research concerning new derivatives has been focused on the modification of one or more portions of such pharmacophore. The combination of structural elements (heterocyclic nucleus, propyl chain and 4-substituted piperazine), known to be critical to the affinity to 5-HT_1A receptors, and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. The most active compounds were selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies were performed. The results of the pharmacological studies showed that Norbo-4 and Norbo-18 were the most active and promising derivatives for the serotonin receptor considered in this study.     

Structure and Reactivity of Al−O(H)−Al Moieties in Siloxide Frameworks: Solution and Gas‐Phase Model Studies

Even though aluminas and aluminosilicates have found widespread application, a consistent molecular understanding of their surface heterogeneity and the behavior of defects resulting from hydroxylation/dehydroxylation remains unclear. Here, we study the well‐defined molecular model compound, [Al₃(μ₂‐OH)₃(THF)₃(PhSi(OSiPh₂O)₃)₂], 1 , to gain insight into the acid–base reactivity of cyclic trinuclear Al₃(μ₂‐OH)₃ moieties at the atomic level. We find that, like zeolites, they are sufficiently acidic to catalyze the isomerization of olefins. DFT and gas phase vibrational spectroscopy on solvent‐free and deprotonated 1 show that the six‐membered ring structure of its Al₃(μ₂‐OH)₃ core is unstable with respect to deprotonation of one of its hydroxy groups and rearranges into two edge‐sharing four‐membered rings. This renders Al_IV?O(H)?Al_IV units strong acid sites, and all results together suggest that their acidity is similar to that of zeolitic Si_IV?O(H)?Al_IV groups.     

New convergence results on functional iteration techniques for the numerical solution of M/G/1 type Markov chains

Summary. By performing an accurate analysis of the convergence, we give a complete theoretical explanation of the experimental behaviour of functional iteration techniques for the computation of the minimal nonnegative solution of the matrix equation , arising in the numerical solution of M/G/1 type Markov chains (here the 's are nonnegative matrices such that the matrix is column stochastic). Moreover, we introduce a general class of functional iteration methods, which includes the standard methods, and we give an optimality convergence result in this class. Received September 1, 1995 / Revised version received September 9, 1996     

F 2-FDG NMR imaging of the brain in rat

Images of the rat head reflecting glucose utilization were obtained using 2-fluoro-2-deoxy-D-glucose (2-FDG) and ¹⁹F nuclear magnetic resonance (NMR) imaging. Spatial heterogeneity of glucose utilization in the rat head was clearly demonstrated showing significantly higher glucose utilization in the brain as compared to the surrounding tissues. Although the potential adverse effects of the high doses of 2-FDG (400 mg/kg) needed to perform the study preclude immediate application of this technique to clinical quantitative glucose utilization studies, the present study shows potential for future development of glucose utilization imaging by NMR.