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Le traitement de la crise de migraine consiste le plus souvent en la prise d’antalgiques, specifiques ou non. Un traitement de fond, prophylactique, peut egalement etre instaure. Neanmoins, le pharmacien a la possibilite de proposer une prise en charge alternative au patient, sans pour autant supprimer les traitements allopathiques.

International audience; Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

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International audience; Within the last 25 years, matrix-assisted laser desorption ionization (MALDI) has become a powerful analytical tool in mass spectrometry (MS). While the method has been successfully applied to characterize large organic molecules such as proteins, sugars and polymers, its utilization for small molecules (≤ 600 Da) is significantly impaired by the coformation of matrix ions. Reducing or eliminating matrix-related signals has been subject of many studies. Some of which propose the enhancement of so-called matrix suppression effects, while others suggest the replacement of matrix molecules by materials such as microporous silicon. Alternatively, the immobilization of matrix molecules by utilizing them as self-assembled monolayers (SAMs) has been discussed. In continuation of this research, the current manuscript focuses on the elucidation of ion formation processes occurring on the surface of light absorbing SAMs. Ion yields obtained by free and immobilized matrix molecules as well as those generated by matrix-free gold film-assisted laser desorption ionization (GF-LDI) were compared. Experiments showed that the formation of strong analyte signals essentially required the presence of free matrix molecules, while the immobilization of the latter severely impaired ionization. The observed effect inversely correlated with the surface coverage of SAMs determined by cyclic voltammetry (CV). Based on these findings, the MS signal generated on light absorbing SAMs could be used supplementary to CV for determining the surface coverage of light absorbing SAMs.

L’arrivee de l’hiver s’accompagne de celle de moult petits maux. De ce fait, le pharmacien est frequemment sollicite par des clients souhaitant eviter ces petits tracas ou s’en debarrasser rapidement. Ils sont aussi demandeurs de remedes efficaces pour combattre la fatigue.

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International audience; Polyphenolic compounds have created an increasing interest for their potency about cardiovascular diseases for several years1-2. Nevertheless, most of this research had been focused on polyphenolic compound such as flavanols (e.g. catechine from tea), anthocyanin (e.g. delphinidin from blueberry) and stilbenoides (e.g. resveratrol from grape).The present study was designed to screen the potent effect of polyphenolic compounds isolated from plants belonging to Clusiaceae family on endothelium. A huge number of polyphenols such as xanthones and coumarines have been identified from those species and some of them exhibiting various biological activities such as anti-inflammatory and antioxidant properties3-4. Their effect on endothelium, more particularly on angiogenesis, is not yet well-known. Firstly, we assessed the capacity of six molecules to induce endothelium-dependent relaxation in mice aortic rings involving nitric oxide production. Isocalolongic acid (A1) and 2-deprenylrheediaxanthone (A2) are able to increase NO production on endothelial cells and to induce endothelium-dependant relaxation. Then, we investigated the effects of these compounds on in vitro and ex vivo angiogenesis. We showed that A1 treatment promoted the formation of capillary-like network contrary to A2. Endothelial cell adhesion, migration and proliferation were decreased in presence of A2 whereas endothelial migration and proliferation were improved with A1 treatment. We could explain these results with the capacity of A1 to increase VEGF expression and for A2, to decrease ICAM-1 expression. Thus, the strategy used for the screening allows the detection of active molecules from Clusiaceae family that might be of therapeutic benefit in cardiovascular diseases5.

International audience; The inhibiting effect of two Schiff bases on the corrosion of the mild steel (MS) in 1 M HCl has been studied by electrochemical impedance spectroscopy (EIS) and Tafel polarisation measurements. The Schiff bases, 4,4′-bis(3-carboxaldehyde thiophene) diphenyl diimino ether (L1) and 4,4′-bis(3-carboxaldehyde thiophene) diphenyl diimino ethane (L2), were synthesized using 3-carboxaldehydethiophene and its corresponding amine. Polarisation curves reveal that both compounds are mixed type (cathodic/anodic) inhibitors and inhibition efficiency (% IE) increases with increasing concentration of compounds. It is suggested that their effects depend on their concentrations and the molecular structures. Adsorption of compounds on mild steel surface is spontaneous and obeys Langmuir's isotherm. Research highlights ► The aim of the present investigation is to examine the inhibitory action of two Schiff bases. ► Compounds are mixed type (cathodic/anodic) inhibitors. ► Inhibition efficiency (% IE) increases with increasing concentration of compounds. ► Adsorption of compounds on mild steel surface obeys Langmuir's isotherm.

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The complete structure of N-methyl-12-ethoxy-2,3,8,9-tetramethoxybenzo[c]phenanthridinium methylsulfonate salt 1, also named ethoxidine, was established by a single-crystal X-ray analysis. The crystal is triclinic, space group $$ P\overline{1}$$ with a = 14.1836 (11), b = 14.2803 (11), c = 14.3073 (12) A, β = 77.699 (5)°, V = 2422.3 (3) A3, Z = 4, 2 C25H29NO8S, D c = 1.381 g/cm3, μ (CuKα) = 1.5418 A, S = 1.036, F (000) = 1064.00, R = 0.0594 and wR = 0.1446. In the unit cell, there are two independent molecules. Solid-state data could be used to enlighten the biological mechanism of action. The complete structure of N-methyl-12-ethoxy-2,3,8,9-tetramethoxybenzo[c]phenanthridinium methylsulfonate salt 1, also named ethoxidine, was established unequivocally by a single-crystal X-ray analysis.

Chlorogenic acid (5-caffeoyl quinic acid (CQA)) extracted from Hydrangea macrophylla (44%, w/w) with 98% purity, was acylated with palmitic acid by Novozym 435 to yield mono-acylated CQA. Acylation of CQA was achieved in 2-methyl-2-butanol at 60°C, and yielded two mono-acylated products: a major product acylated at the C-4 of the quinic moiety (4-O-palmitoyl chlorogenic acid) and a minor product acylated at the C-3 (3-O-palmitoyl chlorogenic acid). The bioconversions obtained in 7 days ranged from 14 to 60% and were influenced by the molar ratio of palmitic acid/CQA, which ranged from 10 to 80. The regioselectivity (4-O-palmitoyl/3-O-palmitoyl ratio) of the reaction was also affected by the molar ratio, and ranged from 90 to 70%. The scavenging activities against 1,1-diphenyl-2-picryl-hydrazyl radicals demonstrated that these palmitoyl CQA derivatives are associated with antioxidant activity (70% vs CQA).

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International audience; Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis (CF). While usually responsible for chronic colonization without clinical signs, this fungus may cause severe and often lethal infections in lung transplant recipients. Early diagnosis of its airway colonization and appropriate treatment are required to eradicate the fungus when a lung transplantation is planned. Here we propose an alternative to mycological examination of sputum samples based on extraction of siderophores by chromatography on Amberlite XAD-4, followed by high performance liquid chromatography analysis of the siderophore extract. Improvement of the extraction procedure was performed in a fractional factorial design which revealed the importance of prior ammonium sulfate precipitation of the proteins, alkalinization of the obtained solution and stirring during extraction. In order to verify the specificity of Nα-methyl coprogen B for S. apiospermum, the method was applied on culture supernatants of different filamentous fungi colonizing the airways of CF patients, including some aspergilli and Exophiala dermatitidis. Nα-methyl coprogen B was detected exclusively for species of the S. apiospermum complex. Likewise, sputum samples from colonized and non-colonized CF patients were analyzed, and the siderophore was detected exclusively in three out of the five specimens which were found by culture to contain S. apiospermum. Together these results confirmed Nα-methyl coprogen B as a marker of the airway colonization by species of the S. apiospermum complex.

Date du colloque: 04/2010; National audience

International audience; Flavonoids are a group of polyphenol compounds with known antioxidant activities. Among them, dihydrochalcones are mainly found in apple leaves (Malus domestica). Glycosylated dihydrochalcones were previously found in large amounts in leaves of two genotypes of Malus with contrasting resistance to fire blight, a bacterial disease caused by Erwinia amylovora. In the present study we demonstrate that soluble polyphenol patterns comprised phloridzin alone or in combination with two additional dihydrochalcones, identified as sieboldin and trilobatin. Presence of sieboldin in young leaves correlated well with a high 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Moreover, these leaves displayed enhanced tolerance to paraquat, a photooxidative-stress generating herbicide. Interestingly, phloridzin had a high activity in the oxygen radical absorbance capacity (ORAC) assay, but its presence alone in leaves did not correlate with tolerance to paraquat. In order to further characterise the activity of these compounds, we tested their ability to prevent oxidative-dependent formation of advanced glycation end-products (AGEs) and phenylephrine-induced contraction of isolated rat mesenteric arteries. The antioxidant capacity of sieboldin was clearly demonstrated by showing that this compound (i) prevented vasoconstriction and (ii) inhibited AGEs formation. Both assays provided interesting information concerning a potential use of sieboldin as a therapeutic. Hence, our results strongly argue for a bioactivity of dihydrochalcones as functional antioxidants in the resistance of Malus leaves to oxidative stress. In addition, we demonstrate for the first time that sieboldin is a powerful multipotent antioxidant, effective in preventing physiopathological processes. Further work should aim at demonstrating the potential use of this compound as a therapeutic in treating free radical-involving diseases.

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International audience; Alkaloids from Thalictrum flavum L. (Ranuculaceae) growing in the Loire valley (France) were isolated and evaluated for their antiplasmodial and leishmanicidal activities. Berberine was identified as a major component but its analogue, pseudoberberine, was isolated for the first time from this plant. As far as bisbenzylisoquinolines are concerned, thalfoetidine was also isolated and, besides, its nor- derivative, northalfoetidine, was identified as a new compound. Previously isolated alkaloids from Thalictrum species such as northalidasine, northalrugosidine, thaligosidine, thalicberine, thaliglucinone, preocoteine, O-methylcassythine and armepavine were newly described in the roots of T. flavum. Tertiary isoquinolines, and particularly bisbenzylisoquinolines, were found to be leishmanicidal against L. major. Thalfoetidine appeared as the most potent but its new nor- derivative northalfoetidine, as well as northalidasine, were of particular interest due to the fact that their potential leishmanicidal activity was not associated to a strong cytotoxicity.

International audience; Les parents d’un nourrisson sont souvent très préoccupés par les petits troubles pouvant affecter leur enfant, notamment lors des tous premiers mois. Ces “bobos” sont, de ce fait, très souvent évoqués au comptoir.

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International audience; The trans-fusarinine backbone is a common feature encountered in many fungal siderophores. This monomer is notably the structural base of Nα-methyl coprogen B and dimerumic acid. Both siderophores are known to be secreted by Scedosporium apiospermum, an emerging pathogenic fungus studied for its high involvement in invasive infections of immunocompromised patients. The strategy developed here for the synthesis of the trans-fusarinine scaffold relies on the preparation of both N-hydroxyornithine and 3-anhydroxymevalonic acid subunits starting from l-ornithine and 3-butyn-1-ol, respectively. The coupling of these two building blocks led to the expected protected backbone.

Date du colloque: 05/02/2010

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International audience; The acido-basic and the complexation properties of di-, tri-, and tetra-phosphonic acids (H6L1, H8L2, and H10L3) toward Fe(III) and Cu(II) were determined by potentiometric titration in aqueous media at 25.0 ± 0.1°C with constant ionic strength (0.1 M, NaClO4). We have determined six, ten, and eight pKa values for the di, tri, and tetra-phosphonic acids, respectively. In acidic conditions, e.g., 0 ≤ pH ≤ 5; iron and copper presented a high affinity toward these ligands to give complex species. With the ligand H10L3, [FeL3H7], and [CuL3H6]2− were easily obtained at pH 1.8 and 2.7, respectively. We have determined ten stability constants for the H10L3/Fe system and nine for the H10L3/Cu one; six and four in the cases of H8L2/Fe and H8L2/Cu systems, respectively. Finally, five stability constants were calculated for the H6L1/Fe system and four for the H6L1/Cu one. We have not observed any insoluble species in these complexes in acidic medium as well as in alkaline solutions.

International audience; In the critical search for new antituberculosis lead compounds, bryophytes represent a largely untapped resource of chemically diverse structures. From the liverwortJungermannia exsertifoliasubsp.cordifolia, 11 new trachylobane diterpene derivatives, as well as three known compounds, were isolated. Their structures were elucidated by spectroscopic means, and full1H NMR spin analysis of one model compound confirmed the relative configurational assignments of the congeners. Four of the isolates exhibited noticeable activity against virulentMycobacterium tuberculosisH37Rvwith minimal inhibitory concentrations of 61−24 μg/mL. This finding suggests that bryophytes in general and trachylobanes in particular deserve further attention in the search for new antimycobacterial leads.

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International audience; Advanced glycation end-products (AGEs) are involved in the pathogenesis of numerous affections such as diabetes and neurological diseases. AGEs are also implied in various changes in tissues and organs. Therefore, compounds able to break them or inhibit their formation may be considered as potential drugs, dietary supplements, or bioactive additives. In this study, we have developed a rapid and reliable (Z′ factor calculation) anti-AGEs activity screening based on the overall fluorescence of AGEs. This method was successfully evaluated on known AGEs inhibitors and on a small library of natural compounds, yielding coherent results when compared with literature data.

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Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis (CF) and causing severe infections in immunocompromised hosts. In order to improve our knowledge on the pathogenicity of this fungus, we investigated its production of siderophores. A maximal production was obtained by cultivation of the fungus at alkaline pH in an iron-restricted liquid culture medium. Siderophores were then extracted from the culture filtrate by liquid/liquid extraction, and separated by reverse phase HPLC. Two siderophores, dimerumic acid (DMA) and N-methyl coprogen B (MCB), were identified by electrospray-ionisation-mass spectrometry and MSn fragmentation. Comparison of various fungal isolates suggested a high production of MCB by clinical isolates of respiratory origin. After optimizing the siderophore extraction process, a study of siderophores produced by other fungi isolated in CF patients allows us to identify four new siderophores. As MCB was exclusively detected in sputum of CF patients colonized by S. apiospermum, it could be considered as a diagnostic marker of lung colonization by this fungus which can be detected in sputa. Further studies of the iron acquisition mechanisms by S. apiospermum, require a large scale synthesis of DMA and MCB and analogs. All those molecules contain in their skeleton the fusarinin moiety as monomer. Synthesis of the fusarinin scaffold was achieved with an overall yield of 2% according to a converging strategy from protected ornithin and but-3-yn-1-ol.; Scedosporium apiospermum, pathogène émergent, colonise les voies respiratoires des patients mucoviscidosiques et provoque des infections sévères chez les patients immunodéprimés. Afin d'améliorer notre connaissance sur sa pathogénicité, nous avons étudié sa production en sidérophores. Après une production maximale en milieu de culture liquide déplété en fer et à pH alcalin, les sidérophores ont été récupérés du filtrat de culture par extraction liquide/liquide, et analysés par CLHP en phase inverse. Deux sidérophores, l'acide dimérumique (DMA) et le N-méthyl coprogène B (MCB), ont été identifiés grâce à de la spectrométrie de masse MSn par ionisation par électro-nébulisation. La comparaison des différentes souches fongiques a montré une production importante de MCB pour les isolats cliniques d'origine respiratoire. Après optimisation du protocole d'extraction, de nouveaux sidérophores ont été identifiés à partir d'autres champignons impliqués dans la mucoviscidose. Seul le MCB était présent chez S. apiospermum, constituant ainsi un marqueur de ce champignon. Ainsi, la détection de ce sidérophore dans les expectorations de malades atteints de mucoviscidose pourrait constituer une méthode de diagnostic des infections à S. apiospermum. Dans le but d'étudier plus précisément les mécanismes d'acquisition du fer par S. apiospermum, la synthèse du DMA et du MCB a été entreprise. Ces molécules contiennent respectivement deux à trois monomères de base, la fusarinine. C'est donc la synthèse de la de la fusarinine qui a été effectuée avec un rendement global de 2% en mettant en jeu une synthèse convergente à partir de l'ornithine protégée et du but-3-yn-1-ol.

International audience; The rapid and specific detection of therapeutically important ligands in complex mixtures, that may bind to membrane proteins, remains challenging for many research laboratories and pharmaceutical industries. Through its use in the development of screening assays, mass spectrometry (MS) is currently experiencing a period of tremendous expansion. In the study presented here, we took advantage of the remarkable stability properties of a bacterial membrane protein, the KcsA K+ channel, produced in E. coli and purified as a tetrameric protein in the presence of a detergent. This membrane protein can subserve as a molecular template to display the pore-forming region of human K+ channels, which are considered as targets in the search for inhibitory ligands. The engineered chimeric proteins were linked to metal-bound magnetic beads, for the screening of complex peptide mixtures, such as that of scorpion venoms. The affinity-captured scorpion toxins were eluted prior to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and to nano-electrospray ionization tandem mass QqTOF mass spectrometry (MS/MS) analysis. The de novo sequence of the toxins was deduced by combining the MS/MS fragmentation of the reduced form (up to the 33 first residues) and the trypsin digest peptides of the native toxins. This affinity-capture screening assay led to the isolation and characterization of potent and specific ligands of the human K+ channel, Kv1.3. The affinity-capture procedure is fast and reproducible. When linked to magnetic beads, the chimeric membrane protein can be re-used several times without losing any of its selectivity or specificity. This assay also benefits from the fact that it requires minimal amounts of animal venoms or complex mixtures, which can be expensive or difficult to procure.

International audience; In the title compound, [Ni(C8H7O4)2{(CH3)2SO}2], the NiII atom is located on a crystallographic centre of symmetry and has a distorted octahedral coordination geometry of type MO6. The bidentate dehydroacetic acid (DHA) ligands occupy the equatorial plane of the complex in a trans configuration, and the dimethyl sulfoxide (DMSO) ligands are weakly coordinated through their O atoms in the axial positions.

Date du colloque: 06/2009

International audience; Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis and causing severe infections in immunocompromised hosts. In order to improve our knowledge on the pathogenic mechanisms of this fungus, we investigated the production of siderophores. Cultivation on CAS medium and specific assays for different classes of siderophores suggested the secretion of hydroxamates. A maximal production was obtained by cultivation of the fungus at alkaline pH in an iron-restricted liquid culture medium. Siderophores were then extracted from the culture filtrate by liquid/liquid extraction, and separated by reverse phase high performance liquid chromatography. Two siderophores, dimerumic acid and N α-methyl coprogen B, were identified by electrospray ionization-mass spectrometry and MS–MS fragmentation. Finally, comparison of various strains suggested a higher production of N α-methyl coprogen B by clinical isolates of respiratory origin. Studies are initiated in order to determine the potential usefulness of these siderophores as diagnostic markers of scedosporiosis.

International audience; Two new tropane alkaloid N-oxides substituted by a methylpyrrole moiety were isolated from the bark of Erythroxylum vacciniifolium Mart. (Erythroxylaceae), a Brazilian indigenous plant, locally known as catuaba and used in traditional medicine as an aphrodisiac. The alkaloid structures were determined by a combination of high resolution mass spectrometry and multi-dimensional NMR spectroscopy.

International audience; Anacardium occidentale L. (A. occidentale), belonging to Anacardiaceae family, has been documented as traditional plant for the treatment of diabetes and hypertension [1]. Four extracts of A. occidentale were used for this study, namely AOL1 (from cyclohexane), AOL2 (from CH2Cl2), AOL3 (from EtOAc) and AOL4 (from MeOH). The most potent antiradical reactivity was observed in AOL4 with 2023 TE/g of extract compared to chlorogenic acid (2976 TE/g of compound) as positive standard. In the other hand, our data showed a significant inhibitory effect of EtOAc and MeOH extracts on BSA glycoxidation measured in terms of advanced glycation end products (AGEs). In isolated mesenteric artery rings precontracted with phenylephrine [2], AOL1, AOL2, AOL3, and AOL4 induced a concentration-dependant relaxation respectively with IC50 values of 120µg/ml, 100µg/ml, 70µg/ml and 70µg/ml. Exposure of Eahy cells to high glucose for 7 days significantly (p

Date du colloque: 09/2009

Date du colloque: 04/2009

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