A mechanistic study on the phototoxicity of atorvastatin: singlet oxygen generation by a phenanthrene-like photoproduct

Atorvastatin calcium (ATV) is one of the most frequently prescribed drugs worldwide. Among the adverse effects observed for this lipid-lowering agent, clinical cases of cutaneous adverse reactions have been reported and associated with photosensitivity disorders. Previous work dealing with ATV photochemistry has shown that exposure to natural sunlight in aqueous solution leads to photoproducts resulting from oxidation of the pyrrole ring and from cyclization to a phenanthrene derivative. Laser flash photolysis of ATV, at both 266 and 308 nm, led to a transient spectrum with two maxima at λ ) 360 and λ ) 580 nm (τ ) 41 μs), which was assigned to the primary intermediate of the stilbene-like photocyclization. On the basis of the absence of a triplet-triplet absorption, the role of the parent drug as singlet oxygen photosensitizer can be discarded. By contrast, a stable phenanthrene-like photoproduct would be a good candidate to play this role. Laser flash photolysis of this compound showed a triplet-triplet transient absorption at λmax ) 460 nm with a lifetime of 26 μs, which was efficiently quenched by oxygen (kq ) 3 ((0.2) × 109 M-1 s-1). Its potential to photosensitize formation of singlet oxygen was confirmed by spin trapping experiments, through conversion of TEMP to the stable free radical TEMPO. The photoreactivity of the phenanthrene-like photoproduct was investigated using Trp as a marker. The disappearance of the amino acid fluorescence (λmax ) 340 nm) after increasing irradiation times at 355 nm was taken as a measurement of photodynamic oxidation. To confirm the involvement of a type II mechanism, the same experiment was also performed in D2O; this resulted in a significant enhancement of the reaction rate. On the basis of the obtained photophysical and photochemical results, the phototoxicity of atorvastatin can be attributed to singlet oxygen formation with the phenanthrene-like photoproduct as a photosensitizer

Oscillatory fracture path in thin elastic sheet

We report a novel mode of oscillatory crack propagation when a cutting tip is driven through a thin brittle polymer film. The phenomenon is so robust that it can easily be reproduced at hand (using CD packaging material for example). Careful experiments show that the amplitude and wavelength of the oscillatory crack path scale lineraly with the width of the cutting tip over a wide range of lenghtscales but are independant of the width of thje sheet and the cutting speed. A simple geometric model is presented, which provides a simple but thorough interpretation of the oscillations.Comment: 6 pages, submitted to Comptes Rendus Academie des Sciences. Movies available at http://www.lmm.jussieu.fr/platefractur

Noncritical quadrature squeezing through spontaneous polarization symmetry breaking

We discuss the possibility of generating noncritical quadrature squeezing by spontaneous polarization symmetry breaking. We consider first type-II frequency-degenerate optical parametric oscillators, but discard them for a number of reasons. Then we propose a four-wave mixing cavity in which the polarization of the output mode is always linear but has an arbitrary orientation. We show that in such a cavity complete noise suppression in a quadrature of the output field occurs, irrespective of the parameter values

Rutherford backscattering analysis of the failure of chlorine anodes

Rutherford Backscattering Spectrometry, carried out at the ORNL Surface Modification And Characterization Collaborative Research Center (SMAC) facility, has been applied to the nondestructive analysis of RuO[sub 2]-TiO[sub 2] electrodes of 5000 Angstroms, which mimic the DSA anodes in composition and the method of preparation. Occidental Chemical Corporation provided electrodes, which had been subjected to life time testing in H[sub 2]S04 solution, for analysis by ORNL. The results were used to test the hypothesis of degradation of theses, and similar electrodes, from a process involving a decrease in the RuO[sub 2]:TiO[sub 2] ratio at and near the electrode surface and the related decrease in the electrode electrical conductivity. The drop in electrode activity is closely linked to a decrease in Ru content, and the measured profiles show that the loss takes place across the thin RuO[sub 2]-TiO[sub 2] coating. No build up of a pure TiO[sub 2] layer is apparent. The data agree quantitatively with the critical concentration previously reported by ORNL for materials produced by ion implantation and characterized by Rutherford Backscattering Spectrometry and Photoacoustic Spectrometry. The study has brought a better understanding of the degradation process in electrodes of great technological importance, and has given a more solid background in designing new fabrication procedures for improved electrodes

Acceptability of different oral dosage forms in paediatric patients in hospital setting

Objective The understanding of acceptability of existing dosage forms is limited in most of the world and hinders the development of acceptable, age‐appropriate medicines. The attributes of paediatric medicine acceptability may differ from country to country based on culture, healthcare infrastructure and health policies. This study was designed to map the acceptability of oral medicines in paediatric patients treated in hospital in India. Methods An observational, cross-sectional study was conducted in patients aged below 18 years and taking any form of oral medication. Acceptability scores were obtained using CAST–ClinSearch Acceptability Score Test tool. Findings 490 patients were recruited and 193 evaluations of different pharmaceutical products available in 20 dosage forms and 7 routes of administration were studied. Oral liquids (50%) and tablets (35%) were the most commonly prescribed and administered forms. Regardless of the therapeutic class and age, the oral liquids were ‘positively accepted’ in infants and toddlers. Acceptability of tablets improved with age and appeared to be generally good from the age of 6. Conclusion This study indicates the limited progress towards adoption of age-appropriate dosage forms in India and thus impact on the acceptability of existing oral dosage forms. The key challenges posed by the adoption of age-appropriate formulations in India are (1) awareness of importance of appropriate administration and acceptability of medicines to children in India, (2) availability of age-appropriate dosage forms and (3) lack of child-appropriate medicine policies

Silica Materials for Medical Applications

The two main applications of silica-based materials in medicine and biotechnology, i.e. for bone-repairing devices and for drug delivery systems, are presented and discussed. The influence of the structure and chemical composition in the final characteristics and properties of every silica-based material is also shown as a function of the both applications presented. The adequate combination of the synthesis techniques, template systems and additives leads to the development of materials that merge the bioactive behavior with the drug carrier ability. These systems could be excellent candidates as materials for the development of devices for tissue engineering

Fractal Spin Glass Properties of Low Energy Configurations in the Frenkel-Kontorova chain

We study numerically and analytically the classical one-dimensional Frenkel-Kontorova chain in the regime of pinned phase characterized by phonon gap. Our results show the existence of exponentially many static equilibrium configurations which are exponentially close to the energy of the ground state. The energies of these configurations form a fractal quasi-degenerate band structure which is described on the basis of elementary excitations. Contrary to the ground state, the configurations inside these bands are disordered.Comment: revtex, 9 pages, 9 figure

Strong relative intensity squeezing by 4-wave mixing in Rb vapor

We have measured -3.5 dB (-8.1 dB corrected for losses) relative intensity squeezing between the probe and conjugate beams generated by stimulated, nondegenerate four-wave mixing in hot rubidium vapor. Unlike early observations of squeezing in atomic vapors based on saturation of a two-level system, our scheme uses a resonant nonlinearity based on ground-state coherences in a three-level system. Since this scheme produces narrowband, squeezed light near an atomic resonance it is of interest for experiments involving cold atoms or atomic ensembles.Comment: Submitted to Optics Letter

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

Symbiosis is a dominant form of life that has been observed numerous times in marine ecosystems. For example, macroalgae coexist with bacteria that produce factors that promote algal growth and morphogenesis. The green macroalga Ulva mutabilis (Chlorophyta) develops into a callus-like phenotype in the absence of its essential bacterial symbionts Roseovarius sp. MS2 and Maribacter sp. MS6. Spatially resolved studies are required to understand symbiont interactions at the microscale level. Therefore, we used mass spectrometry profiling and imaging techniques with high spatial resolution and sensitivity to gain a new perspective on the mutualistic interactions between bacteria and macroalgae. Using atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionisation high-resolution mass spectrometry (AP-SMALDI-HRMS), low-molecular-weight polar compounds were identified by comparative metabolomics in the chemosphere of Ulva. Choline (2-hydroxy-N,N,N-trimethylethan-1-aminium) was only determined in the alga grown under axenic conditions, whereas ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) was found in bacterial presence. Ectoine was used as a metabolic marker for localisation studies of Roseovarius sp. within the tripartite community because it was produced exclusively by these bacteria. By combining confocal laser scanning microscopy (cLSM) and AP-SMALDI-HRMS, we proved that Roseovarius sp. MS2 settled mainly in the rhizoidal zone (holdfast) of U. mutabilis. Our findings provide the fundament to decipher bacterial symbioses with multicellular hosts in aquatic ecosystems in an ecologically relevant context. As a versatile tool for microbiome research, the combined AP-SMALDI and cLSM imaging analysis with a resolution to level of a single bacterial cell can be easily applied to other microbial consortia and their hosts. The novelty of this contribution is the use of an in situ setup designed to avoid all types of external contamination and interferences while resolving spatial distributions of metabolites and identifying specific symbiotic bacteria