Evaluation in vitro de la cytotoxicité et de l'effet antioxydant des analogues de prostaglandines antiglaucomateux

Les analogues de prostaglandines en collyre sont les molécules hypotonisantes les plus puissantes disponibles pour traiter la glaucome chronique à angle ouvert. Trois molécules sont disponibles sur le marché avec des efficacités comparables : le Xalatan®, le Travatan® et le Lumigan®. Nous avons comparé, in vitro, sur des cellules conjonctivales épithéliales humaines ces trois produits sous leur forme commerciale et également deux d'entre elles (le latanoprost et le bimatoprost) sous forme non conservée afin d'évaluer leur cytotoxicité et leur effet sur le stress oxydant. Cinq sondes différentes ont été utilisées : le rouge neutre évaluant la viabilité cellulaire, le Hoechst 33342 et le YOPRO-1 évaluant l'apoptose cellulaire et le H2DCF-DA et l'hydroéthidine mettant en évidence respectivement la présence d'espèces réactives de l'oxygène (ERO) et d'anion superoxyde. La cytotoxicité des trois collyres, contenant un agent conservateur, est directement liée à leur concentration en cet agent. Ainsi le Lumigan® présente la cytotoxicité la plus faible, tandis que le Xalatan® se montre le plus cytotoxique. La comparaison entre la viabilité cellulaire induite par ces trois collyres comparées à celle de leur conservateur, testé séparément, permet de mettre en évidence une cytotoxicité statistiquement plus faible pour le Xalatan® et Travatan®. Aucun effet cytoprotecteur n'est retrouvé pour le Lumigan®. Les tests de stress oxydant confirment ce résultat en montrant une diminution statistiquement significative des ERO détectées avec le Xalatan® et le Travatan® comparés à leur conservateur respectif. Les tests menés avec le latanoprost et le bimatoprost non conservés montrent des résultats similaires avec un effet antioxydant statistiquement significatif pour le latanoprost semblant augmenter avec sa concentration. En revanche cet effet n'est pas retrouvé avec le bimaprost. La cytotoxicité in vitro des analogues de prostaglandines est liée à leur concentration en conservateur. Le latanoprost et travoprost présentent un effet cytoprotecteur antioxydant jusqu'alors jamais décritProstaglandin analogs are actually the most efficient drugs to treat chronical glaucoma. Three molecules are available with similar efficiency : Xalatan®, Travatan® and Lumigan®. We compared in vitro on human conjunctiva-derived epithelial cells, the three eyedrops in their commercial presentation and two of them (latanoprost and bimatoprost) in a preservative-free solution, in order to evaluate their toxicity and their action on oxidative stress. Five probes were used : neutral red to evaluate cellular viability, Hoechst 33342 and Yopro-1 to evaluate apoptosis, and H2DCF-DA and hydroethidine to detect the reactive oxygen species (ROS). Cytotoxicity of the three eyedrops was directly related to their concentration in preservative (benzalkonium chloride = BAC). Thus, Lumigan® which contains the lower concentration of preservative appeared the less toxic, while Xalatan® showed the higher toxicity. Comparison between the three eyedrops and their respective BAC highlighted a statistical significant reduction of toxicity with Xalatan® and Travatan®. No cytoprotective action was found with Lumigan®. Oxidative stress assays confirmed this result showing a significant reductio of ROS detected with the cells exposed to Xalatan® and Travatan®, compared with their respective preservative. The results obtained with the unpreserved latanoprost and bimatoprost were similar, with an antioxidative action statistically significant for latanoprost and no antioxidative property for bimatoprost. In vitro cytotoxicity of prostaglandin analogs was related to their concentration of benzalkonium chloride. Latanoprost and travoprost presented an unknown cytoprotective and antioxidative effect...PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Comparative study of topical anti-allergic eye drops on human conjunctiva-derived cells: responses to histamine and IFNγ and toxicological profiles

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Spontaneous Buckling Induced by the Adsorption of Charged Copolymers at the Air-Water Interface

We present results of the adsorption of charged diblock copolymers at the free interface between air and solution. These copolymers are water soluble and act as surfactants above some concentration. Through thermodynamic and diffuse X-ray surface scattering measurements, we demonstrate the influence of the concentration on the formed adsorbed layer. While sufficiently long copolymers adsorb by forming structures which do not deform the interface, short copolymers are shown to induce buckling of the interface due to interchain interactions

Polymersome Shape Transformation at the Nanoscale

International audiencePolymer vesicles, also named polymersomes, are valuable candidates for drug delivery and micro or nano-reactors applications. As far as drug delivery is concerned, the shape of the carrier is believed to have a strong influence on the biodistribution and cell internalization. Polymersomes can be submitted to an osmotic imbalance when injected in physiological media leading to morphological changes. To understand these osmotic stress-induced variations in membrane properties and shapes, several nano-vesicles made of the graft polymer poly(dimethylsiloxane)-g-poly(ethylene oxide) (PDMS-g-PEO) or the triblock copolymer PEO-b-PDMS-b-PEO were osmotically stressed and observed by light scattering, neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). Hypotonic shock leads to a swelling of the vesicles, comparable to optically observable giant polymersomes, and hypertonic shock leads to collapsed structures such as stomatocytes and original nested vesicles the latter being only observed for diblocks. Complementary SANS and cryo-TEM experiments are shown to be in quantitative agreement and highlight the importance of the membrane structure on the behavior of these nano-polymersomes under hypertonic conditions as the final morphology reached depends whether or not the copolymers assemble into a bilayer. The vesicle radius and membrane curvature are also shown to be critical parameters for such transformations: the shape evolution trajectory agrees with theoretical models only for large enough vesicle radii above a threshold value around four times the membrane thickness

Revealing crystalline domains in a mollusc shell single-crystalline prism

International audienceBiomineralization integrates complex processes leading to an extraordinary diversity of calcareous biomineral crystalline architectures, in intriguing contrast with the consistent presence of a sub-micrometric granular structure. Hence, gaining access to the crystalline architecture at the mesoscale, that is, over a few granules, is key to building realistic biomineralization scenarios. Here we provide the nanoscale spatial arrangement of the crystalline structure within the ‘single-crystalline’ prisms of the prismatic layer of a Pinctada margaritifera shell, exploiting three-dimensional X-ray Bragg ptychography microscopy. We reveal the details of the mesocrystalline organization, evidencing a crystalline coherence extending over a few granules. We additionally prove the existence of larger iso-oriented crystalline domains, slightly misoriented with respect to each other, around one unique rotation axis, and whose shapes are correlated with iso-strain domains. The highlighted mesocrystalline properties support recent biomineralization models involving partial fusion of oriented nanoparticle assembly and/or liquid droplet precursors

Revealing the meso-crystallinity arrangement of a "single-crystalline" calcareous biomineral

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Gender-related differences in the management of hypertension by cardiologists: The PARITE study

SummaryBackgroundSeveral studies have shown gender differences in the management of cardiovascular risk factors and diseases. Whether the management of hypertension by cardiologists in France differs according to patient gender has not been fully investigated.AimsThe main objective of this cross-sectional, multicentre study was to examine the management according to gender of hypertensive patients by office-based cardiologists in France.MethodsCardiologists were asked to include consecutively two men and two women attending a routine consultation for essential hypertension. Therapeutic management was evaluated by comparing cardiovascular investigations in the preceding 6 months and hypertension control according to gender and the patients’ global cardiovascular risk.ResultsOverall, data from 3440 adult patients (53% men) referred to 654 cardiologists were analysed. Hypertension was uncontrolled in 76% of both men and women and 69% were at high global cardiovascular risk (75% of men, 62% of women; P<0.001). Significantly fewer cardiovascular investigations had been performed in the preceding 6 months in women (22.6% vs 44.2% in men; P<0.001). The treatment regimen was changed by the cardiologist in approximately 50% of patients regardless of gender or global cardiovascular risk.ConclusionsThe PARITE study shows that in French office-based cardiology practice, the antihypertensive regimen is adjusted as often in female as in male patients. However, the results suggest that there is room for improvement in the investigation of cardiovascular disease in women. Healthcare providers could be encouraged to implement established guidelines on the prevention of cardiovascular disease in women