Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity

[EN] In the present work, the preparation, characterization and therapeutic potential of baicalin-loaded nanohydrogels are reported. The nanohydrogels were prepared by sonicating (S nanohydrogel) or autoclaving (A nanohydrogel) a dispersion of cholesterol-derivatized gellan in phosphate buffer. The nanohydrogel obtained by autoclave treatment showed the most promising results: smaller particles ( similar to 362 nm vs. similar to 530 nm), higher homogeneity (polydispersity index = similar to 0.24 vs. similar to 0.47), and lower viscosity than those obtained by sonication. In vitro studies demonstrated the ability of the nanohydrogels to favour the deposition of baicalin in the epidermis. A high biocompatibility was found for baicalin-loaded nanohydrogels, along with a great ability to counteract the toxic effect induced by hydrogen peroxide in cells, as the nanohydrogels re-established the normal conditions (similar to 100% viability). Further, the potential of baicalin-loaded nanohydrogels in skin wound healing was demonstrated in vivo in mice by complete skin restoration and inhibition of specific inflammatory markers (i.e., myeloperoxidase, tumor necrosis factor-alpha, and oedema.Financial support from University "Sapienza" - Progetti di Ricerca: grant RP116154C2EF9AC8 and grant RM11715C1743EE89 are acknowledged.Manconi, M.; Manca, M.; Caddeo, C.; Cencetti, C.; Di Meo, C.; Zoratto, N.; Nácher Alonso, A.... (2018). Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity. European Journal of Pharmaceutics and Biopharmaceutics. 127:244-249. https://doi.org/10.1016/j.ejpb.2018.02.015S24424912

Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist

RATIONALE: The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation. OBJECTIVES: We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day). METHODS: We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology. RESULTS: Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip. CONCLUSIONS: Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulatio

Evaluación de riesgo de incidentes agresivos y antisociales en población psiquiátrico forense brasileña

La evaluación del riesgo y el adecuado dimensionamiento de las conductas agresivas y comportamientos antisociales en un hospital psiquiátrico forense es necesaria para evitar prejuicios y para planificar las acciones preventivas correspondientes. El sesgo que producen el comportamiento agresivo y el antisocial puede tener efectos perjudiciales a la hora de planificar la externación. Sin embargo, no existía hasta este estudio información científica sobre la incidencia de estas conductas en hospitales psiquiátrico forenses brasileños.Facultad de Ciencias Médica

Evaluación de riesgo de incidentes agresivos y antisociales en población psiquiátrico forense brasileña

La evaluación del riesgo y el adecuado dimensionamiento de las conductas agresivas y comportamientos antisociales en un hospital psiquiátrico forense es necesaria para evitar prejuicios y para planificar las acciones preventivas correspondientes. El sesgo que producen el comportamiento agresivo y el antisocial puede tener efectos perjudiciales a la hora de planificar la externación. Sin embargo, no existía hasta este estudio información científica sobre la incidencia de estas conductas en hospitales psiquiátrico forenses brasileños.Facultad de Ciencias Médica

Evaluación de riesgo de incidentes agresivos y antisociales en población psiquiátrico forense brasileña

La evaluación del riesgo y el adecuado dimensionamiento de las conductas agresivas y comportamientos antisociales en un hospital psiquiátrico forense es necesaria para evitar prejuicios y para planificar las acciones preventivas correspondientes. El sesgo que producen el comportamiento agresivo y el antisocial puede tener efectos perjudiciales a la hora de planificar la externación. Sin embargo, no existía hasta este estudio información científica sobre la incidencia de estas conductas en hospitales psiquiátrico forenses brasileños.Facultad de Ciencias Médica

Reuso de información en comunidades virtuales

Con el comienzo del nuevo siglo, la Web 2.0 permitió que cualquier usuario con conexión a internet y sin conocimientos especiales, pueda publicar contenido propio mediante herramientas colaborativas como blogs, wikis, y foros de discusión. Al mismo tiempo surgieron plataformas para creación de redes sociales de distinto tipo o con objetivos diferentes, concretamente se destaca el trabajo distribuido colaborativo, el intercambio de conocimiento técnico, académico, científico y lo social. Estas comunidades que fueron formándose a partir de la participación online recibieron el nombre de comunidades virtuales. Durante los últimos años hubo una evolución hacia la Web 3.0 la cual se ocupa de, por un lado, facilitar la accesibilidad a la información sin depender del dispositivo utilizado, y por otro lado, el modo que las personas interactúan con ella para conseguir los resultados que desean. Además, se enfoca en que la información sea compartida de una forma inteligible, que sea útil para los usuarios que recurren a ella y a las necesidades especiales de sus usuarios de acuerdo a las circunstancias. Así, nuestro proyecto se enfocará en proveer modelos de calidad para sistemas software de recuperación, análisis, clasificación y reuso de la información proveniente de comunidades virtuales en la Web.Red de Universidades con Carreras en Informátic

Glucose metabolism enzymes gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer (CRC)

No abstract availabl

Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: In the training cohort (n = 217), the median age was 69 years (range: 32–89), and the primary tumours were non–small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60–3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31–3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13–2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs