New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.

Estrategias de gestión y comunicación de los líderes intermedios en la aplicación de los ECTS

Los datos que se utilizan en este artículo proceden de una investigación sobre el Proceso de Bolonia llevada a cabo en diez titulaciones de una sola universidad; seis de ellas forman parte del proyecto piloto para incorporar los European Credit Transfer System (ECTS). En este trabajo, nos centramos en cómo los líderes intermedios de las titulaciones piloto estudiadas ponen en marcha la implementación de los ECTS siguiendo estrategias diferenciadas de gestión, generación de consenso y comunicación. Asimismo, se examinan las respuestas que el profesorado de las mismas titulaciones da, en términos de valoración de la gestión, las actitudes ante la reforma y el grado de información percibido. El análisis nos permite identificar algunas oportunidades y constricciones ¿derivadas de las formas de gestión consideradas legítimas por los miembros de esta institución universitaria¿ ante las que se sitúa la acción de los líderes intermedios.

Annuaire-Chaix : annuaire officiel des chemins de fer publié par l'administration de l'Imprimerie centrale des Chemins de fer

1852-1853.

Decreasing educational differences in mortality over 40 years: evidence from the Turin Longitudinal Study (Italy)

BACKGROUND: Recent studies suggest that inequalities in premature mortality have continued to rise over the last decade in most European countries, but not in southern European countries. METHODS: In this study, we assess long-term trends (1971-2011) in absolute and relative educational inequalities in all-cause and cause-specific mortality in the Turin Longitudinal Study (Turin, Italy), a record-linkage study including all individuals resident in Turin in the 1971, 1981, 1991 and 2001 censuses, and aged 30-99 years (more than 2 million people). We examined mortality for all causes, cardiovascular disease (CVD), all cancers and specific cancers (lung, breast), as well as smoking and alcohol-related mortality. RESULTS: Overall mortality substantially decreased in all educational groups over the study period, although cancer rates only slightly declined. Absolute inequalities decreased for both genders (SII=962/694 in men/women in 1972-1976 and SII=531/259 in 2007-2011, p<0.01). Among men, absolute inequalities for CVD and alcohol-related causes declined (p<0.05), while remaining stable for other causes of death. Among women, declines in absolute inequalities were observed for CVD, smoking and alcohol-related causes and lung cancer (p<0.05). Relative inequalities in all-cause mortality remained stable for men and decreased for women (RII=1.92/2.03 in men/women in 1972-1976 and RII=2.15/1.32 in 2007-2011). Among men, relative inequalities increased for smoking-related causes, while among women they decreased for all cancers, CVD, smoking-related causes and lung cancer (p<0.05). CONCLUSIONS: Absolute inequalities in mortality strongly declined over the study period in both genders. Relative educational inequalities in mortality were generally stable among men; while they tended to narrow among women. In general, this study supports the hypothesis that educational inequalities in mortality have decreased in southern European countries.

Annuaire des postes, ou Manuel du service de la poste aux lettres : à l'usage du commerce et des voyageurs / publié par ordre de l'administration

1843.

Annuaire des postes, ou Manuel du service de la poste aux lettres : à l'usage du commerce et des voyageurs / publié par ordre de l'administration

1901.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1861.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1863.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1859-1860.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1865-1866.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1869 (T9)-1871.

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1868 (T8).

Annuaire encyclopédique : politique, économie sociale, statistique, administration, sciences, littérature, beaux-arts, agriculture, commerce, industrie / publié par les directeurs de l'Encyclopédie du XIXe siècle

1867.