Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation

Purpose. To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods. Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg ®). Results. Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30 % (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion. The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. KEY WORDS: drug release; enzymatic degradation; meta-tetra(hydroxyphenyl)chlorin (mTHPC); photodynamic therapy (PDT); polymeric micelles

C-fos and c-myc modulation, mitogenic effect and Ia expression in the P388D1 murine macrophage line treated by immunomodifiers.

The aim of the present study was to investigate whether the early modulation of the c-fos and c-myc oncogenes could give some orientation to the impact of immunomodulators on the monocyte-macrophage lineage. In order to work in a homogeneous system we used the P388D1 mouse macrophage cell-line which is considered as an almost mature macrophage. When P388D1 cells were stimulated by LPS, interferon-gamma or the association of both compounds, no direct correlation could be found between the modulation of DNA synthesis and the early expression of the c-fos and c-myc oncogenes. The positive regulation of Ia antigen expression seemed to correlate with the absence of induction of c-fos oncogene

Nasolacrimal duct office probing in children under the age of 12 months: Cure rate and cost evaluation.

International audienceINTRODUCTION:Controversy exists regarding the treatment of infants with symptomatic nasolacrimal duct obstruction. One philosophy advocates "early" nasolacrimal duct probing, generally in the office - a relatively common approach in France, while others prefer to wait until the age of 12 months to offer a procedure under general anesthesia. The goal of this study is to report results of immediate office probing for congenital nasolacrimal duct obstruction (CNLDO) under age 1 year in terms of efficacy and cost.METHODS:A retrospective study was performed on 329 patients (443 eyes) treated by probing for CNLDO under the age of 12 months age. A single probing was performed at the first visit in the office under topical anesthesia without sedation. In order to determine the factors associated with failure of probing, univariate analysis was performed using the Student t-test, Pearson's, homogeneity Chi(2) or Fisher's exact tests. For cost evaluation, hypothetical estimates of spontaneous resolution month by month were used according to data in the literature, along with health insurance reimbursement data.RESULTS:The ages of the patients ranged from 2 to 11 months (mean 7.0 ± SD 2.3). The overall success rate for cure by immediate office probing was 76.7%. Unilateral CNLDO had an 80.4% success rate whereas bilateral CNLDO had a 73.2% success rate for each eye (P=0.09). Discharge during probing was associated with failed probing (P=0.02). The cost for the spontaneous resolution strategy was 1.56 times higher than for the immediate probing strategy. A strategy which would apply the spontaneous resolution strategy for children ≤ 5 months and the probing strategy to children>5 months would be the most cost-effective.CONCLUSIONS:Immediate office probing between the ages of 5 to 12 months is a safe, effective method to relieve CNLDO and is the most cost-effective

The Codevelopment of Mangroves and Infaunal Community Diversity in Response to the Natural Dynamics of Mud Deposition in French Guiana

The sustainability of mangrove ecosystems requires a knowledge of their spatiotemporal variability as a function of regional properties. The unique coastal ecosystems of the mangrove belt along the coast of the Guianas in South America are influenced by cycles of a massive accretion of mud supplied by the Amazon River and wave induced erosion. This study characterized, for the first time, how benthic infaunal assemblages, as proxies of mechanisms of mangrove resilience, were structured by the natural growth track of Avicennia germinans dominated mangroves in French Guiana. We sampled 4 mobile mud stations and 27 consolidated mud stations distributed over 9 tidal transects from bare to vegetated mudflats colonized by young mangroves during the dry season. We collected a complete dataset of sediment and vegetation variables together with the benthic meso- (>0.25 mm) and macrofauna (>1 mm). We used a combination of eigenvector based multivariate analyses and variance partitioning on this multiple set of variables to identify which environmental variables likely drive the benthic diversity patterns. Mangrove early development increased the alpha and beta diversities of the infaunal communities for the two size classes. A total of 20–30% and 7–12% of the beta diversity are explained by linear and nonlinear spatial variables, respectively. However, 7% to 9% of the variance partioning could be determined by other biotic/abiotic variables, biological interactions or neutral processes, not described here. This study has highlighted the necessity of taking into account mangrove dynamics at suitable spatial scales for benthic biodiversity evaluation and mangrove management or restoration plan

Imaging Time-Resolved Electrothermal Atomization Laser-Excited Atomic Fluorescence Spectrometry for Determination of Mercury in Seawater

International audienceIn this study, direct determination of mercury at the nanogram per liter level in the complex seawater matrix by imaging time-resolved electrothermal atomization laser-excited atomic fluorescence spectrometry (ITR-ETA-LEAFS) is described. In the case of mercury, the use of a nonresonant line for fluorescence detection with only one laser excitation is not possible. For measurements at the 253.652 nm resonant line, scattering phenomena have been minimized by eliminating the simultaneous vaporization of salts and by using temporal resolution and the imaging mode of the camera. Electrothermal conditions (0.1 M oxalic acid as matrix modifier, low atomization temperature) have been optimized in order to suppress chemical interferences and to obtain a good separation of specific signal and seawater background signal. For ETA-LEAFS, a specific response has been obtained for Hg with the use of time resolution. Moreover, an important improvement of the detection limit has been obtained by selecting, from the furnace image, pixels collecting the lowest number of scattered photons. Using optimal experimental conditions, a detection limit of 10 ng L–1 for 10 μL of sample, close to the lowest concentration level of total Hg in the open ocean, has been obtained