Phototoxicity of protoporphyrin IX, diarginine diprotoporphyrinate and N,N-diphenylalanyl protoporphyrin toward human fibroblasts and keratinocytes in vitro: effect of 5-methoxypsoralen

The phototoxicity of two new porphyrin photosensitizers, diarginine diprotoporphyrinate (PP(Arg)2) and N,N-diphenylalanyl protoporphyrin (PP(Phe)2), and the synergistic effect of 5-methoxyposralen (5-MOP) have been studied in comparison with that of protoporphyrin IX (PPIX). Under ultraviolet-A (UV-A) irradiation (lambda=365 nm), the phototoxicity of the porphyrins toward cultured human fibroblasts and keratinocytes decreases in the order: PPIX > PP(Arg)2 > PP(Phe)2. A synergistic effect of 5-MOP on the phototoxicity of PPIX, PP(Arg)2 and PP(Phe)2 has been observed. The combination of PPIX, PP(Arg)2 and PP(Phe)2 with 0.1-0.5 microM 5-MOP significantly potentiates the phototoxicity of the three porphyrins. The most effective potentiation was observed with the water-soluble PP(Arg)2 and 5-MOP concentrations lower than 0.75 microM. Above this 5-MOP concentration this potentiation is abolished. The intracellular concentration of PPIX and PP(Phe)2 is independent of the presence of 5-MOP. On the other hand, the intracellular content of PP(Arg)2 is decreased in a concentration-dependent manner by the psoralen. Illumination with red light, not absorbed by 5-MOP, leads to a weak potentiation of the PP(Arg)2 phototoxic effect in the presence of 5-MOP, suggesting that dark interaction of 5-MOP with cell membranes aggravated by porphyrin photosensitization is involved in the observed phenomena. The results are tentatively explained by differences in hydrophobicity and molecular structures of the examined photosensitizers. PPIX, which is barely soluble in water, has a significantly higher affinity for cell membranes and simultaneously exerts a stronger phototoxic effect than PP(Arg)2 whose solubility in water is high. On the other hand, the weak phototoxicity of PP(Phe)2 could be explained by the steric hindrance brought by the phenylalanyl substituents on the pyrrole ring. The loss in the PP(Arg)2 cell content probably explains the inhibition of the synergistic effect of 5-MOP on the PP(Arg)2 phototoxicity at high 5-MOP concentration. This study suggests that PP(Arg)2 in combination with 5-MOP might reveal a strong phototoxic effect when applied to skin cancer treatment.     

Conformational analysis of some ortho-hydroxyazoic dyes by the PCILO method

The quantum mechanical MO method PCILO is used to perform a detailed conformational analysis of ortho-hydroxyazobenzene and 1-phenyl azo 2-napthol. Several energy minima are obtained for each compound, after a simultaneous optimization of the main geometric parameters. Comparison is made with the corresponding para compounds. The calculated results are discussed in relation to the available experimental data.     

Single dibenzoterrylene molecules in an anthracene crystal: main insertion sites.

We present a spectroscopic study of the properties of the two principal insertion sites (at 785.1 and 794.3 nm) of single dibenzoterrylene molecules in anthracene single crystals at cryogenic temperatures. We measured the temperature dependence of the line width, the orientation of the transition dipole moments, and the Stark effect. We performed molecular dynamics simulations, which show that one dibenzoterrylene molecule preferably replaces three anthracene molecules. From simulated annealing, we derive the molecular conformations in the most stable insertion sites and the orientations of the transition dipole moments. The good agreement between the spectroscopic results and the simulations allows us to propose unambiguous structures for the two principal spectroscopic sites.     

Determination of salbutamol enantiomers in human urine using heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin in nonaqueous capillary electrophoresis

Nonaqueous capillary electrophoresis (NACE) was successfully applied to the resolution and the determination of salbutamol enantiomers in urine samples using heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin (HDAS-beta-CD). After optimization of the electrophoretic parameters, namely the background electrolyte (BGE) composition and the HDAS-beta-CD concentration, salbutamol enantiomers were completely resolved using a BGE made up of 10 mM ammonium formate and 15 mM HDAS-beta-CD in methanol acidified with 0.75 M formic acid. Isoprenaline was selected as internal standard. Solid-phase extraction (SPE) was used for sample cleanup prior to the CE separation. Different sorbents involving polar, nonpolar interactions or dual retention mechanisms were evaluated and extraction cartridges containing both nonpolar and strong cation-exchange functionalities were finally selected. Salbutamol enantiomers recoveries from urine samples were determined. The method was then successfully validated using a new approach based on accuracy profiles over a concentration range from 375 to 7500 ng/mL for each enantiomer.     

Synthesis,and in vitro and in vivo evaluation of a diphenylchlorin sensitizer for photodynamic therapy

This paper reports the synthesis of a new diphenylchlorin photosensitizer, 2,3-dihydro-5,15-di(3,5-dihydroxyphenyl)porphyrin (SIM01). The photodynamic properties, cell uptake and localization of SIM01 were compared with those of structurally related meso-tetra(hydroxyphenyl)chlorin (m-THPC). In vitro studies were conducted on rat glioma cells (C6) and human adenocarcinoma (HT-29), and in vivo studies on human colon adenocarcinoma cells (HT-29) and human prostate adenocarcinoma cells (PC3). Both dyes showed an absorption maximum at around 650 nm, with a molar extinction coefficient of 13017 M(-1) cm(-1) for SIM01 and 22718 M(-1) cm(-1) for m-THPC. Their capacity to generate singlet oxygen was identical, but differences in partition coefficients indicated that SIM01 was slightly more hydrophilic. In vitro, SIM01 was slightly more phototoxic than m-THPC for C6 cells (4.8 vs. 6.8 microg ml(-1)). However, phototoxicities were nearly identical for HT29 cells (0.45 microg ml(-1) for 5 h incubation followed by 300 mW, 20 J cm(-2)). Pharmacokinetics in vivo in mice, as determined by fibre spectrofluorimetry, showed that the SIM01 fluorescence signal in the tumor was maximal between 6 and 12 h after injection, as compared to 72 h for m-THPC. With a 2 mg kg(-1) dye dose and laser irradiation at 300 J cm(-2) (650 nm, 300 mW), the optimal PDT response occurred when the interval between injection and irradiation was 6 h for SIM01 and 24 h for m-THPC. For SIM01 with 5 mg kg(-1) injection, the optimal PDT response occurred with a 12 h delay and with the same irradiation parameters as described above, in this case the tumor response showing 40% growth. Considering the tumor volume doubling time, the value was 6.5 days in the control group and increased to 13.5 days with SIM01. Thus, SIM01 may be a powerful sensitizer characterized by strong in vitro and in vivo phototoxicity and faster tissue uptake and elimination than m-THPC.     

Ram extrusion force for a frictional plastic material: model prediction and application to cement paste

We developed a model to predict the ram extrusion force of frictional plastic materials such as cement-based pastes. The extrusion of cement-based materials has already been studied, but the interaction between shaping force and paste behaviour still have to be understood. Our model is based on the plastic frictional behaviour of cement-based materials and integrates the physical mechanisms that govern material extrusion flow and extrusion force increase. When the process starts, a pressure gradient is created in the extruder due to wall friction of the paste that is submitted to plug flow. It induces a consolidation of the material. As a result, a large increase of extrusion force appears. A Coulomb law is used to model cement-based materials, which is considered as consolidating granular media. Such modelling is compared with experimental results. Tests were carried out on extrudible cement pastes. Modelling and experimental results are in good agreement.Paper presented at the Annual European Rheology Conference, Grenoble, April 2005     

Two-dimensional modeling of an aircraft engine structural bladed disk-casing modal interaction

In modern turbo machines such as aircraft jet engines, structural contacts between the casing and bladed disk may occur through a variety of mechanisms: coincidence of vibration modes, thermal deformation of the casing, rotor imbalance due to design uncertainties to name a few. These nonlinear interactions may result in severe damage to both structures and it is important to understand the physical circumstances under which they occur. In this study, we focus on a modal coincidence during which the vibrations of each structure take the form of a k-nodal diameter traveling wave characteristic of axi-symmetric geometries. A realistic two-dimensional model of the casing and bladed disk is introduced in order to predict the occurrence of this very specific interaction phenomenon versus the rotation speed of the engine. The equations of motion are solved using an explicit time integration scheme in conjunction with the Lagrange multiplier method where friction is accounted for. This model is validated from the comparison with an analytical solution. The numerical results show that the structures may experience different kinds of behaviors (namely damped, sustained and divergent motions) mainly depending on the rotational velocity of the bladed disk.     

New formulations and valid inequalities for a bilevel pricing problem

Consider the problem of maximizing the toll revenue collected on a multi-commodity transportation network. This fits a bilevel framework where a leader sets tolls, while users respond by selecting cheapest paths to their destination. We propose novel formulations of the problem, together with valid inequalities yielding improved algorithms.     

Bilevel programming: A survey

This paper provides an introductory survey of a class of optimization problems known as bilevel programming. We motivate this class through a simple application, and then proceed with the general formulation of bilevel programs. We consider various cases (linear, linear-quadratic, nonlinear), describe their main properties and give an overview of solution approaches.Received: April 2005, Revised: May 2005, AMS classification: 90C05, 90C11, 90C20, 90C27, 90C3D, 65K05     

Hauteur des sous-schémas toriques et dualité de Legendre–Fenchel

We announce a formula for the height of a complete toric variety defined over a number field. The exact expression rests on tools from convex analysis and in particular, on the Legendre–Fenchel dual of the logarithm of the local norms of a natural section of the relevant metrized line bundle. We apply this formula to the computation of the height of projective toric curves and of toric bundles. To cite this article: J.I. Burgos Gil et al., C. R. Acad. Sci. Paris, Ser. I 347 (2009).