Indirect detection of photosensitizer ex vivo

Photodynamic therapy induces the production of reactive oxygen species (ROS) within tissues exposed to laser light after administration of a sensitizer. In the context of continuing clinical and commercial development of chemicals with sensitizing properties, a minimally invasive assay is needed to determine the tissue kinetics of fluorescent or non-fluorescent photoreactive drugs. The level of ROS was determined ex vivo from 1 mm3 biopsy samples using 2'-7' dichlorofluorescin diacetate (DCFH-DA), a fluorescent probe which was converted into highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This assay was tested on meta(tetrahydroxyphenyl)chlorin (m-THPC, FOSCAN), a powerful and fluorescent sensitizer, and bacteriochlorophyll derivative WST09 (TOOKAD), a near-infrared absorbing sensitizer that is only slightly fluorescent. In conjunction with the ROS assay, the tissue accumulation of m-THPC was determined on biopsy samples using an optic fibre spectrofluorometer (OFS). DCF fluorescence was proportional to the level of oxidation induced by horseradish peroxidase used as a control and to the concentration (range: 0-5 microg x ml(-1)) of both selected photosensitizers irradiated in a tube together with DCFH. Regardless of the organ studied, an excellent correlation was found between fluorescence measurement by OFS and ROS determination for m-THPC. m-THPC (2 mg x kg(-1) iv) accumulation in tumour tissues was best after 48 h, and the best signal was obtained in liver. With non-fluorescent WST09 (2 mg x kg(-1)), ROS determination showed the best tumour uptake 48 h after injection, with a tumour/muscle ratio of 5.4. The ROS assay appears to be feasible for determining sensitizer concentration in regular grip biopsy tissue samples.     

Iodine transfer copolymerization of vinylidene fluoride and α‐trifluoromethacrylic acid in emulsion process without any surfactants

The synthesis of poly(VDF‐co‐TFMA) copolymers (where VDF and TFMA stand for vinylidene fluoride and α‐trifluoromethacrylic acid, respectively) by iodine transfer polymerization without any surfactant is presented. First, the synthesis and the control of the copolymerization of VDF and TFMA were investigated in the presence of two chain transfer agents, 1‐perfluorohexyl iodide (C₆F₁₃I) and 1,4‐diodoperfluorobutane (IC₄F₈I). TFMA monomer was incorporated in the copolymer in good yields. Moreover, the molecular weights of the resulting poly(VDF‐co‐TFMA) copolymers were in good agreement with the theoretical values for feed of TFMA/VDF ratios that ranged from 50/50 to 0/100 mol %, showing that TFMA does not disturb the controlled radical polymerization of VDF. The microstructures of the produced copolymers were characterized by ¹H and ¹⁹F NMR to assess the amount of each comonomer, and the molecular weights and the end‐groups of the copolymers. The results on the control of the copolymerization were compared to those obtained with and without the presences of TFMA and surfactant. The addition of a low amount of TFMA improved the control of the polymerization of VDF without using any surfactant. Also, the size of particles, assessed by light scattering, was smaller than 200 nm. The addition of TFMA in low proportions, that is, 5 to 10 mol %, enabled us to stabilize the particle size and to decrease the size by one order of magnitude. The emulsifying behavior of TFMA (in low amount in the copolymer, that is, <10 mol %) was similar to those achieved when a surfactant was added. Indeed, neither sedimentation nor destabilization was observed after several days. The reactivity ratios for r_TFMA and r_VDF were 0 and 1.6 at 80 °C, respectively. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4710–4722, 2009     

The action modes of Lippia sidoides (Cham) essential oil as penetration enhancers on snake skin

The aim of this work was to study the effect of Lippia sidoides essential oil (LSEO) on stratum corneum lipids and the permeation of salicylic acid. DSC and FTIR spectroscopy were applied. LSEO 1% (v/v) significantly enhanced salicylic acid flux through snake skin. According to the DSC curves changes in the transition temperature of the lipids were observed indicating that LSEO can interact with stratum corneum. The IR spectrum of skin treated with LSEO showed a decrease in the peak intensity for CH₂ stretchings (2920–2850 cm^–1) however the peak positions did not alter suggesting the extraction of the lipids.     

Bioanalysis of small-molecule drugs in nasal and paranasal tissues and secretions: Current status and perspectives

Over the last years, interest in intranasal administration as an alternative and promising route for the delivery of drugs withlocal, systemic, and even central nervous system action has tremendously increased. Accordingly, understanding of the propertiesand characteristics of the nasal cavity as well as the biodisposition processes of drugs into the nasal compartments is acquiringa significant prominence in the field of pharmacology. In this context, the development and validation of bioanalytical methodologies for the quantitative measurement of drugs and their metabolites in nasal and paranasal tissues and/or secretions is of the utmostimportance. However, currently, information concerning bioanalysis of drugs in nasal and paranasal tissues and/or secretionsis scattered. This review aims to provide a valuable overview of the methodologies that have been used for the collectionand preparation of nasal and paranasal samples with special emphasis placed on the review of liquid chromatographic methodsemployed for the quantitative determination of small-molecule drugs and their metabolites in such specimens.      

Extending the QCR method to general mixed-integer programs

Let (MQP) be a general mixed integer quadratic program that consists of minimizing a quadratic function subject to linear constraints. In this paper, we present a convex reformulation of (MQP), i.e. we reformulate (MQP) into an equivalent program, with a convex objective function. Such a reformulation can be solved by a standard solver that uses a branch and bound algorithm. We prove that our reformulation is the best one within a convex reformulation scheme, from the continuous relaxation point of view. This reformulation, that we call MIQCR (Mixed Integer Quadratic Convex Reformulation), is based on the solution of an SDP relaxation of (MQP). Computational experiences are carried out with instances of (MQP) including one equality constraint or one inequality constraint. The results show that most of the considered instances with up to 40 variables can be solved in 1?h of CPU time by a standard solver.     

Site partitioning of Cr3+ in the trichroic alexandrite BeAl2O4:Cr3+ crystal: contribution from x-ray absorption spectroscopy

X-ray absorption spectroscopy measurements at the Cr K-edge of a trichroic crystal of alexandrite BeAl(2)O(4):Cr(3+) for different orientations of the crystal with respect to the polarization and direction of the x-ray incident beam have been performed. Analysis of the experimental spectra with the help of first-principles calculations of x-ray absorption spectra allowed us to estimate the proportion of chromium Cr(3+) cations among the two different octahedral sites of the alexandrite structure (70% in the C(s) site-30% in the C(i) site). The methodology presented in this work opens up new possibilities in the field of mineralogy for the study of complex minerals containing several sites potentially occupied by several transition elements or for solid solutions.     

Reduction of iron by decarboxylation in the formation of magnetite nanoparticles

The process of formation of magnetite nanoparticles has been investigated by liquid chromatography and mass spectroscopy in the liquid phase decomposition of either Fe(III) acetylacetonate with decanoic acid or Fe(III) decanoate. In both cases, the dissociation into radicals of the iron carboxylate bonds provides the reduction of the Fe(III) cations and the oxygen atoms required for the formation of the mixed-valence inverse spinel magnetite structure. A reaction mechanism is proposed. It is also shown that the reaction of free decanoic acid with the Fe(III) cations in solution promotes the growth of faceted particles at the reflux temperature of the solvent (ca. 280 °C), while, under the same conditions, the stepwise decomposition of the Fe(III) decanoate generates smaller and pseudo-spherical particles. The latter also yields faceted particles when the temperature is increased above that of the total decomposition of the salt. Magnetic measurements make evident that the reaction starting from Fe(III) acetylacetonate yields nanoparticles with higher magnetization and lower spin disorder, due to the improved regularity of the surface crystal structure. The starting conditions for the decarboxylation process thus affect the morphology and magnetic properties of the resulting nanoparticles.     

Minimal Submanifolds in Sp+3 with Constant Scalar Curvature

Let M be a compact, minimal 3-dimensional submanifold with constant scalar curvature R immersed in the standard sphere S^3+p. In codimension 1, we know from the work that has been done on Chern’s conjecture that M is isoparametric and R = 3D0, R = 3D3 or R = 3D6. In this paper we extend this result from codimension one to compact submanifolds with a flat normal bundle and give a complete classification.     

X-ray crystal structure of 2-styrylpyridine

We have crystallized the 2-styrylpyridine from the condensation reaction between the 2-methylpyridine with benzaldehyde in the formation of the model compound 2-styrylpyridine. The X-ray structure and NMR are currently reported. The main features of the structure is that is shows a localization of the double bonds rather than a delocalization of π electrons in an aromatic fashion.     

Ferromagnetic phases due to competing short- and long-range interactions in the spin-5/2 and spin-2 Blume–Capel model

We broaden the study of the statistical physics of the spin-S Blume–Capel model with ferromagnetic mean-field interactions J in competition with short-range antiferromagnetic interactions K in a linear chain in the thermodynamic limit. This work is dedicated to the case when S takes the half-integer spin $S=5/2$ and when S assumes the integer value $S=2$. In both cases the phase diagrams exhibit new ferromagnetic phases (for certain values of K) enclosed by branches emerging from the first-order frontiers of the pure ferromagnetic model. For finite temperatures the complex topologies were obtained by numerical minimization of the free energy and some results were confirmed by Monte Carlo simulations.