Redox signaling responses to laminar shear stress in vascular endothelial cells

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21-06-201

Protocol for a randomized controlled dismantling study of an internet-based intervention for depressive symptoms: exploring the contribution of behavioral activation and positive psychotherapy strategies

Background: there are evidence-based interventions for depression that include different components. However, the efficacy of their therapeutic components is unknown. Another important issue related to depression interventions is that, up to now, their therapeutic components have only focused on reducing negative symptoms rather than on improving positive affect and well-being. Because the low levels of positive affect are more strongly linked to depression than to other emotional disorders, it is important to include this variable as an important treatment target. Positive psychotherapeutic strategies (PPs) could help in this issue. The results obtained so far are consistent and promising, showing that Internet-based interventions are effective in treating depression. However, most of them are also multi-component, and it is important to make progress in investigating what each component contributes to the intervention. Methods: the current study will be a three-armed, simple-blinded, randomized controlled clinical trial with a dismantling design. 192 participants will be randomly assigned to: a) an Internet-based Global Protocol condition, which includes traditional therapeutic components of evidence-based treatments for depression (Motivation for change, Psychoeducation, Cognitive Therapy, Behavioral Activation (BA), Relapse Prevention) and PPs component, offering strategies to enhance positive mood and promote psychological strengths; b) an Internet-based BA Protocol condition (without the PPs component), and c) an Internet-based PPs Protocol condition (without the BA component). Primary outcome measures will be the BDI-II and PANAS. Secondary outcomes will include other variables such as depression, anxiety and stress, quality of life, resilience, and wellbeing related measures. Treatment acceptance and usability will also be measured. Participants will be assessed at pre-, post-treatment, 3-, 6- and 12- month follow- ups. The data will be analyzed based on the Intention-to-treat principle. Per protocol analyses will also be performed. Discussion: to the best of our knowledge, this is the first randomized dismantling intervention study for depression with the aim of exploring the contribution of a PPs component and the BA component in an Internet-based intervention. The three protocols are online interventions, helping to reach many people who need psychological treatments and otherwise would not have access to them

Hydrogen peroxide signaling in vascular endothelial cells

Redox signaling is implicated in different physiological and pathological events in the vasculature. Among the different reactive oxygen species, hydrogen peroxide (H2O2) is a very good candidate to perform functions as an intracellular messenger in the regulation of several biological events. In this review, we summarize the main physiological sources of H2O2 in the endothelium and the molecular mechanisms by which it is able to act as a signaling mediator in the vasculature

Role of PTEN in modulation of ADP-dependent signaling pathways in vascular endothelial cells

ADP plays critical signaling roles in the vascular endothelium. ADP receptors are targeted by several cardiovascular drugs, yet the intracellular pathways modulated by ADP are incompletely understood. These studies have identified important roles for the phosphatase PTEN in ADP-dependent modulation of the endothelial isoform of nitric oxide synthase (eNOS) as well as of lipid and protein kinase pathways in endothelial cells. We find that ADP-promoted eNOS activation as well as phosphorylation of p38 MAPK are enhanced by siRNA-mediated PTEN knockdown. However, the increase in ADP-dependent eNOS activation promoted by PTEN knockdown is abrogated by siRNA-mediated knockdown of p38 MAPK. These findings indicate that PTEN tonically suppresses both p38 phosphorylation as well as ADP-stimulated eNOS activity. A key enzymatic activity of PTEN is its role as a lipid phosphatase, catalyzing the dephosphorylation of phosphoinositol-3,4,5-trisphosphate (PIP3) to phosphoinositol-4,5-bisphosphate (PIP2). We performed biochemical analyses of cellular phospholipids in endothelial cells to show that siRNA-mediated PTEN knockdown leads to a marked increase in PIP3. Because these complex lipids activate the small GTPase Rac1, we explored the role of PTEN in ADP-modulated Rac1 activation. We used a FRET biosensor for Rac1 to show that ADP-dependent Rac1 activation is blocked by siRNA-mediated PTEN knockdown. We then exploited a FRET biosensor for PIP3 to show that the striking ADP-dependent increase in intracellular PIP3 is entirely blocked by PTEN knockdown. These studies identify a key role for PTEN in the modulation of lipid mediators involved in ADP receptor-regulated endothelial signaling pathways involving eNOS activation in vascular endothelial cells. © 2013 Elsevier B.V.National Institutes of Health (HL46457, HL48743, GM36259); Ministerio de Economía y Competitividad; Fundación Renal “Iñigo Álvarez deToledo”; Fundación “Ramón Areces”Peer Reviewe

Diurnal and seasonal variation of BTEX in the air of Monterrey, Mexico: preliminary study of sources and photochemical ozone pollution

Atmospheric levels of benzene, toluene, ethylbenzene, and xylenes (BTEX) were measured in an urban site located in Nuevo Leon, Mexico, during summer and autumn 2013. A total of 60 samples were collected using carbon-packed cartridges at 0900, 1200, and 1500 h and then analyzed using gas chromatography with flame ionization detector. Meterological parameters and criteria air pollutants were measured and correlated with BTEX by a principal component analysis (PCA). The relative abundance of BTEX followed the order: benzene > toluene > ethylbenzene > p-xylene with mean concentrations of 55.24 μg m−3, 22.24 μg m−3, 6.94 μg m−3, and 4.17 μg m−3, respectively, during summer. Mean concentrations during autumn were 21.079 μg m−3 for benzene, 3.648 μg m−3 for toluene, 2.521 μg m−3 for ethylbenzene, and 2.115 μg m−3 for p-xylene. All measured BTEX showed clear diurnal and seasonal patterns. The highest mean levels for benzene were obtained during the midday. Toluene, ethylbenzene, and p-xylene showed the highest levels during afternoon period. BTEX levels were higher when wind blew from NE and ESE during summer and from ESE during autumn. The municipalities of Apodaca and Guadalupe are located in these directions where important industries, high traffic volume, many oil and gas service stations, and the biggest airport in this region are found. These sources could contribute to the BTEX concentrations measured during the sampling period