Protein kinase B (AKT) upregulation and Thy-1-αvß3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

BACKGROUND: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvß3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. METHODS: Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). RESULTS: The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. CONCLUSIONS: Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.

Encapsulation of Gold Nanostructures and Oil-in-Water Nanocarriers in Microgels with Biomedical Potential.

Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11⁻12 °C) than nanospheres (1⁻2 °C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications.

Percibirse sin apoyo social predispone al intento suicida / Perceived as lack of social support predisposes to suicide attempt

Se determinan las relaciones de apoyo social percibido y de los eventos vitales, en treinta y nuevo mujeres que han cometido un intento suicida reciente. El primero se asoció a desesperanza, ideación suicida, depresividad y gravedad de la tentativa. Los eventos vitales no se asocian a variable alguna. Se discute el papel del apoyo social percibido en la precipitación de una conducta suicidad y su implicancia clínica.

Social support and life events are determined in thirthy nine parasuicide women and their associations are established. The former is correlated to hopelessness, suicide ideation, depression and severity of intent. Life events had not relationship. Finally, the influence of perceived social support in suicide is discussed.

Expresión verbal de ansiedad en pacientes intentadoras de suicidios / Verbal expression of anxiety in attempters suicide patients

Se investigó la expresión verbal de ansiedad mediante análisis de contenido, en 46 mujeres intentadoras de suicidios de nivel socioeconómico bajo. La ansiedad de separación fue la más frecuente, y su mayor prevalencia se observó en pacientes con diagnósticos de depresión mayor y de trastorno de adaptación con ánimo depresivo. Casi la mitad de las pacientes con distimia evidenciaron niveles elevados de ansiedad de muerte. Otras formas, como ansiedad de culpa y difusa, fueron más evidentes en los trastornos de adaptación con rasgos emocionales mixtos y ansiosos. Los hallazgos corroboran la relevancia de los eventos de pérdida y de la ansiedad de separación en sujetos que han intentado suicidarse

Disfunción erectiva: revisión clínica y actualización / Erectile dysfunction: clinical review and update

Este trabajo pretende entregar una visión actualizada de la disfunción erectiva. Para esto se revisa la fisiología de la erección señalando la contribución de diversos factores en la impotencia; se analiza el problema del diagnóstico diferencial entre disfunciones de etiología orgánica y psicógenas, y se señalan la necesidad de la evaluación de ambos tipos de factores. Finalmente se trata distintos conceptos y visiones respecto a la disfunción erectiva psicógena, así como sus indicaciones terapéuticas. Se analiza la interacción entre disfunción erectiva y conflicto de pareja. Se presenta algunos problemas clínicos y sugerencias de tratamiento