Susceptibility gradient quantization by MRI signal response mapping (SIRMA) to dephaser

Purpose: Susceptibility effects are a very efficient source of contrast in magnetic resonance imaging. However, detection is hampered by the fact the induced contrast is negative. In this work, the SIgnal Response MApping (SIRMA) to dephaser method is proposed to map susceptibility gradient to improve visualization. Methods: In conventional gradient echo acquisitions, the echo formation of susceptibility affected spins is shifted in k -space, the shift being proportional to the susceptibility gradient. Susceptibility gradients map can be produced by measuring this induced shifts. The SIRMA method measures these shifts from a series of dephased images collected with additional incremental dephasers. These additional dephasers correspond either to a slice refocusing gradient offset or to a reconstruction window off-centering. The signal intensity profile as a function of the additional dephaser was determined on a pixel-by-pixel basis from the ensemble of dephased images. Susceptibility affected voxels presented a signal response profile maximum shifted compared to nonaffected voxels ones. Shift magnitude and sign were measured for each pixel to determine susceptibility gradients and produce a susceptibility gradient map. Results: In vitro experiments demonstrated the ability of the method to map gradient inhomogeneities induced by a cylinder. Quantization accuracy was evaluated comparing SIRMA images and simulations performed on the well-characterized air filled cylinder model. Performances of the SIRMA method, evaluated in vitro on cylinders filled with various superparamagnetic iron oxide SPIO concentrations, showed limited influence of acquisition parameters. Robustness of the method was then assessed in vivo after an infusion of SPIO-loaded nanocapsules into the rat brain using a convection-enhanced drug delivery approach. The region of massive susceptibility gradient induced by the SPIO-loaded nanocapsules was clearly delineated on SIRMA maps and images were compared to T 2 weighted images, Susceptibility Gradient Map (SGM), and histological Perl\u27s staining slice. The potential for quantitative evaluation of SPIO distribution volume was demonstrated. Conclusions: The proposed method is a promising technique for a wide range of applications especially in molecular or cellular imaging with respect to its quantitative nature and its computational simplicity

Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors

Application of our original photooxidation–reduction methodology to prenylated dihydroxycoumarin and trihydroxyxanthone compounds led to the corresponding ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives with yields ranging from 8 to 65%. In most of the reported experiments, the oxidation products distribution, after the photooxygenation step, was controlled by the competition between the large group effect and the stabilising phenolic assistance effect. We also showed that ortho-(3-hydroxy-3-methylbut-1-enyl)phenol derivatives could be considered as biogenetic precursors of 2,2-dimethylbenzopyranic structures

Propriétés antibactériennes d’extraits de propolis contre des souches de Staphylococcus aureus sensibles ou résistantes à la méthicilline

La résistance aux antibiotiques est devenue l\u27un des problèmes majeurs de santé publique du XXIème siècle. Il existe donc un réel intérêt thérapeutique dans la recherche de composés ou d\u27extraits naturels capables de limiter cette résistance. La propolis est un mélange complexe composé de substances résineuses collectées par les abeilles sur différentes parties des plantes et arbres, de cires et de sécrétions salivaires de l\u27abeille. Elle sert principalement à colmater les interstices des parois de la ruche et comme véritable arme chimique contre les microorganismes. La propolis est utilisée depuis longtemps en médecine traditionnelle puisqu\u27elle possède des propriétés pharmacologiques intéressantes notamment antioxydante, anti-inflammatoire mais aussi antimicrobienne. Un échantillon de propolis, composé de 24 lots collectés en France (majoritairement dans le sud-ouest) en 2010 et 2011, a été extrait par différents solvants : EtOH 70%, MeOH, DCM et DCM/MeOH/eau 31/19/4 (mixte). La composition chimique des extraits a préalablement été déterminée au moyen d’analyses HPLC/DAD/MS et RMN 1H et 13C. L\u27activité antibactérienne a été évaluée sur des bactéries responsables d\u27infections nosocomiales, et plus spécifiquement sur 13 souches de Staphylococcus aureus [ATCC25923, six isolats cliniques de souches résistantes à la méthiciline (SARM) et six isolats cliniques de souches sensibles à la méthiciline (SASM)] par détermination de la concentration minimum d\u27inhibition (CMI) en milieu gélosé [1]. Les résultats ont montré que, parmi les quatre extraits, le DCM et le "mixte" présentaient une bonne activité antibactérienne contre S. aureus (SA) avec des CMI respectives de 60±10 et 67±15 µg/mL mais également sur quasiment toutes les souches SARM et SASM testées (CMI entre 30 et 97 µg/mL). Ces bonnes activités des extraits DCM et mixte peuvent être reliées à des teneurs élevées en polyphénols totaux et en flavonoïdes [1]. Diverses études ont en effet montré que ce type de mélange complexe, riche en polyphénols, était plus actif que les composés isolés les constituant. Les polyphénols agiraient ainsi de façon synergique, potentialisant l\u27activité antibactérienne de ces extraits [2]. D\u27autres études, menées in vitro, ont par ailleurs mis en évidence un réel synergisme entre propolis et antibiotiques [3], [4]. Ainsi, ces extraits de propolis présentent-ils un réel potentiel dans une lutte alternative contre des infections à staphylocoques.   Références [1]          S. Boisard et al., "Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis", Evid. Based Complement. Alternat. Med., vol. 2015, p. e319240, 2015. [2]          A. Kujumgiev, I. Tsvetkova, Y. Serkedjieva, V. Bankova, R. Christov, et S. Popov, "Antibacterial, antifungal and antiviral activity of propolis of different geographic origin", J. Ethnopharmacol., vol. 64, no 3, p. 235‑240, 1999. [3]          S. Stepanović, N. Antić, I. Dakić, et M. Švabić-Vlahović, "In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs", Microbiol. Res., vol. 158, no 4, p. 353‑357, 2003. [4]          A. Fernandes Júnior, E. C. Balestrin, J. E. C. Betoni, R. de O. Orsi, M. de L. R. de S. da Cunha, et A. C. Montelli, "Propolis: anti-Staphylococcus aureus activity and synergism with antimicrobial drugs", Mem. Inst. Oswaldo Cruz, vol. 100, no 5, p. 563‑566, 2005

Screening an in house alkaloids library using Voltage-Sensor Probes for new modulators of voltage-gated sodium channels

Voltage-gated sodium channels (Nav) are molecular targets of clinically used drugs for treatments of various diseases (epilepsy, chronic pain, cardiac arrhythmia…) and also of numerous animal and plant neurotoxins. The development of easy-to-use screening assays for searching new ligands from chemicals libraries, animal venoms or plant extracts represents a challenge of a great interest to generate therapeutic hits. Here, we used the mammalian GH3B6 pituitary cell line, which constitutively expresses three different neuronal Nav channel isoforms (Nav1.2, Nav1.3 and Nav1.6), to identify novel compounds of pharmacological interest from a library of in-house vegetal alkaloids. The screening is based on a method using Voltage-Sensor Probes (VSPs) that we adapted to detect both activators and blockers of Nav channels. Over the 84 pure alkaloids or plant extracts that were screened, 17 increased the VSP signal. They operated as gating modifier, showing an action mechanism similar to that of batrachotoxin (BTX), known to strongly inhibit Nav channel inactivation. The remaining 67 plant products were assessed for their potency to inhibit BTX-induced VSP signal. We further selected 11 alkaloids as efficient Nav channels inhibitors. We focused our attention on two structural analogs belonging to the aporphine family, liriodenine and oxostephanine, which differ only by a methoxy group. Whereas liriodenine has been already described as a Nav channels blocker, oxostephanine has not been yet documented as an ion channel modulator. In conclusion, the novel VSPs-based screening assay we developed is a suitable method to challenge the discovery and to assess the activity of novel ligands on Nav channels

First 2-Hydroxy-3-Methylbut-3-Enyl Substituted Xanthones Isolated From Plants: Structure Elucidation, Synthesis and Antifungal Activity

Two new 2-hydroxy-3-methylbut-3-enyl substituted xanthones, ( - )-caledol 1 and ( - )-dicaledol 2 were isolated from a dichloromethane extract of the leaves of Calophyllum caledonicum (Clusiaceae). Compounds 1 and 2 are the first 2-hydroxy-3-methylbut-3-enyl substituted xanthones isolated from natural source. Their structures were elucidated by means of combined analytical methods including HRFABMS, 1D and 2D NMR spectroscopies and also confirmed by total synthesis using biomimetic ortho -prenylphenols photooxygenation ( 1 O 2 ) as a key step. The antifungal activity against Aspergillus fumigatus is reported

From dereplication and anti-inflammatory screening of Clusiaceae and Calophyllaceae species to novel immunomodulatory coumarins from Mesua lepidota

Vascular endothelium plays a central role in the development of inflammatory and immune processes, which are involved in graft rejection1. Many Clusiaceae/Calophyllaceae species (pantropical plants) biosynthesize original polyphenolic compounds exhibiting antioxidant and anti-inflammatory properties2-3. Bark, leaves and occasionally fruits from thirteen Malaysian plants belonging to the genus Calophyllum, Mesua (Calophyllaceae), Garcinia (Clusiaceae) were extracted using DCM and MeOH as the solvents. Each extract was then submitted to a HPLC-PDA-MSn dereplication analysis and its anti-inflammatory potential was evaluated on Human Umbilical Vein Endothelial Cells (HUVECs). This allowed to select the bioactive fruits DCM extract of Mesua lepidota T. Anderson for an advanced phytochemical study, which led to the identification of several new coumarin derivatives. A flow cytometry study revealed that the major component of this extract, namely lepidotol A (1), significantly inhibited the VCAM-1, HLA-II and HLA-E expression of HUVECs previously activated by TNF-α or IFN-γ cytokines.   References   1.     P. T. Clesca, Int. Congr. Ser., 2002, 1237, 181-191. 2.     F. V. Cechinel, C. Meyre-Silva, and R. Niero, Chem. Biodivers., 2009, 6, 313-327. 3.     J. González-Gallego, M. V. García-Mediavilla, S. Sánchez-Campos and M. J. Tuñón, Br. J. Nutr., 2010, 104, S15-S2

Chemical composition and antiglycoxidant activities of French organic propolis extracts

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