Susceptibility of clinical isolates of bacteria to cefamandole, cefoxitin and cephalothin

The in vitro susceptibility was determined of 274 isolates to cephalothin and two new antibiotics, cefamandole and cefoxitin. Cefamandole was comparable to cephalothin in preventing growth of cultures of the gram positive organisms except for penicillin-resistant Staphylococcus aureus which was more sensitive to cephalothin. Cefamandole was more active than cephalothin against all the gram negative bacteria including Haemophilus influenzae and in addition it was active against many strains of Enterobacter sp. Cefoxitin was less active than cephalothin against the gram positive organisms but it was more active against most of the gram negative bacteria. In addition. It was active against Serratia and indole positive Proteus which are uniformly resistant to cephalothin

Conformationally-Locked C-Glycosides: Tuning Aglycone Interactions for Optimal Cheperone Behaviour in Gaucher Fibroblasts

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver β-glucosidase/β-galactosidase and specific inhibition of human β-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound AmbroxolMinisterio de Economía y Competitividad CTQ2012-36365, SAF2013-44021-RJunta de Andalucía FQM-1467European Union Seventh Framework Programme FP7-People-2012-CI

Epilepsia Refractaria

Se realiza una revisión de los antecedentes históricos, epidemiológicos y clínicos de la Epilepsia Refractaria y los aspectos relacionados con la cirugía como tratamiento no farmacológico de elección en los síndromes remediables quirúrgicamente que se describen. Los objetivos de la cirugía, la preevaluación y sus resultados son analizados

Photoionization in the time and frequency domain

Ultrafast processes in matter, such as the electron emission following light absorption, can now be studied using ultrashort light pulses of attosecond duration ($10^{-18}$s) in the extreme ultraviolet spectral range. The lack of spectral resolution due to the use of short light pulses may raise serious issues in the interpretation of the experimental results and the comparison with detailed theoretical calculations. Here, we determine photoionization time delays in neon atoms over a 40 eV energy range with an interferometric technique combining high temporal and spectral resolution. We spectrally disentangle direct ionization from ionization with shake up, where a second electron is left in an excited state, thus obtaining excellent agreement with theoretical calculations and thereby solving a puzzle raised by seven-year-old measurements. Our experimental approach does not have conceptual limits, allowing us to foresee, with the help of upcoming laser technology, ultra-high resolution time-frequency studies from the visible to the x-ray range.Comment: 5 pages, 4 figure

MEMPHYS:A large scale water Cerenkov detector at Fr\'ejus

A water \v{C}erenkov detector project, of megaton scale, to be installed in the Fr\'ejus underground site and dedicated to nucleon decay, neutrinos from supernovae, solar and atmospheric neutrinos, as well as neutrinos from a super-beam and/or a beta-beam coming from CERN, is presented and compared with competitor projects in Japan and in the USA. The performances of the European project are discussed, including the possibility to measure the mixing angle $\theta_{13}$ and the CP-violating phase $\delta$.Comment: 1+33 pages, 14 figures, Expression of Interest of MEMPHYS projec

Anticancer and antibacterial potential of robust Ruthenium(II) arene complexes regulated by choice of α-diimine and halide ligands

Several complexes of general formula [Ru(halide)(η6-p-cymene)(α-diimine)]+, in the form of nitrate, triflate and hexafluorophosphate salts, including a newly synthesized iodide compound, were investigated as potential anticancer drugs and bactericides. NMR and UV–Vis studies evidenced remarkable stability of the complexes in water and cell culture medium. In general, the complexes displayed strong cytotoxicity against A2780 and A549 cancer cell lines with IC50 values in the low micromolar range, and one complex (RUCYN) emerged as the most promising one, with a significant selectivity compared to the non-cancerous HEK293 cell line. A variable affinity of the complexes for BSA and DNA binding was ascertained by spectrophotometry/fluorimetry, circular dichroism, electrophoresis and viscometry. The performance of RUCYN appears associated to enhanced cell internalization, favored by two cyclohexyl substituents, rather than to specific interaction with the evaluated biomolecules. The chloride/iodide replacement, in one case, led to increased cellular uptake and cytotoxicity at the expense of selectivity, and tuned DNA binding towards intercalation. Complexes with iodide or a valproate bioactive fragment exhibited the best antimicrobial profiles