The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation

The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.

ROS as signalling molecules in T cells - Evidence for abnormal redox signalling in the autoimmune disease, rheumatoid arthritis

Reactive oxygen species are recognised as important signalling molecules within cells of the immune system. This is, at least in part, due to the reversible activation of kinases, phosphatases and transcription factors by modification of critical thiol residues. However, in the chronic inflammatory disease rheumatoid arthritis, cells of the immune system are exposed to increased levels of oxidative stress and the T cell becomes refractory to growth and death stimuli. This contributes to the perpetuation of the immune response. As many of the effective therapies used in the treatment of rheumatoid arthritis modulate intracellular redox state, this raises the question of whether increased oxidative stress is causative of T-cell hyporesponsiveness. To address this hypothesis, this review considers the putative sources of ROS involved in normal intracellular signalling in T cells and the evidence in support of abnormal ROS fluxes contributing to T-cell hyporesponsiveness. © W. S. Maney & Son Ltd.

Ceramide and reactive oxygen species (ROS) as signal transduction molecules in inflammation

Reactive oxygen species (ROS) and the sphingolipid ceramide are each partly responsible for the intracellular signal transduction of a variety of physiological, pharmacological or environmental agents. Furthermore, the enhanced production of many of these agents, that utilise ROS and ceramide as signalling intermediates, is associated with the aetiologies of several vascular diseases (e.g. atherosclerosis) or disorders of inflammatory origin (e.g. rheumatoid arthritis; RA). Excessive monocyte recruitment and uncontrolled T cell activation are both strongly implicated in the chronic inflammatory responses that are associated with these pathologies. Therefore the aims of this thesis are (1) to further elucidate the cellular responses to modulations in intracellular ceramide/ROS levels in monocytes and T cells, in order to help resolve the mechanisms of progression of these diseases and (2) to examine both existing agents (methotrexate) and novel targets for possible therapeutic manipulation. Utilising synthetic, short chain ceramide to mimic the cellular responses to fluctuations in natural endogenous ceramide or, stimulation of CD95 to induce ceramide formation, it is described here that ceramide targets and manipulates two discrete sites responsible for ROS generation, preceding the cellular responses of growth arrest in U937 monocytes and apoptosis in Jurkat T-cells. In both cell types, transient elevations in mitochondrial ROS generation were observed. However, the prominent redox altering effects appear to be the ceramide-mediated reduction in cytosolic peroxide, the magnitude of which dictates in part the cellular response in U937 monocytes, Jurkat T-cells and primary human peripheral blood resting or PHA-activated T-cells in vitro. The application of synthetic ceramides to U937 monocytes for short (2 hours) or long (16 hours) treatment periods reduced the membrane expression of proteins associated with cell-cell interaction. Furthermore, ceramide treated U937 monocytes demonstrated reduced adhesion to 5 or 24 hour LPS activated human umbilical vein endothelial cells (HUVEC) but not resting HUVEC. Consequently it is hypothesised that the targeted treatment of monocytes from patients with cardiovascular diseases with short chain synthetic ceramide may reduce disease progression. Herein, the anti-inflammatory and immunosuppressant drug, methotrexate, is described to require ROS production for the induction of cytostasis or cytotoxicity in U937 monocytes and Jurkat T-cells respectively. Further, ROS are critical for methotrexate to abrogate monocyte interaction with activated HUVEC in vitro. The histological feature of RA of enhanced infiltration, survivability and hyporesponsiveness of T-cells within the diseased synovium has been suggested to arise from aberrant signalling. No difference in the concentrations of endogenous T-cell ceramide, the related lipid diacylglycerol (DAG) and cytosolic peroxide ex vivo was observed. TCR activation following PHA exposure in vitro for 72 hours did not induced maintained perturbations in DAG or ceramide in T-cells from RA patients or healthy individuals. However, T-cells from RA patients failed to upregulate cytosolic peroxide in response to PHA, unlike those from normals, despite expressing identical levels of the activation marker CD25. This inability to upregulate cytosolic peroxide may contribute to the T-cell pathology associated with RA by affecting the signalling capacity of redox sensitive biomolecules. These data highlight the importance of two distinctive cellular pools of ROS in mediating complex biological events associated with inflammatory disease and suggest that modulation of cellular ceramides represents a novel therapeutic strategy to minimise monocyte recruitment.

Chemical specificity in REDOX-responsive materials:the diverse effects of different Reactive Oxygen Species (ROS) on polysulfide nanoparticles

REDOX responsive (nano)materials typically exhibit chemical changes in response to the presence and concentration of oxidants/reductants. Due to the complexity of biological environments, it is critical to ascertain whether the chemical response may depend on the chemical details of the stimulus, in addition to its REDOX potential, and whether chemically different responses can determine a different overall performance of the material. Here, we have used oxidation-sensitive materials, although these considerations can be extended also to reducible ones. In particular, we have used poly(propylene sulfide) (PPS) nanoparticles coated with a PEGylated emulsifier (Pluronic F127); inter alia, we here present also an improved preparative method. The nanoparticles were exposed to two Reactive Oxygen Species (ROS) typically encountered in inflammatory reactions, hydrogen peroxide (H2O2) and hypochlorite (ClO−); their response was evaluated with a variety of techniques, including diffusion NMR spectroscopy that allowed to separately characterize the chemically different colloidal species produced. The two oxidants triggered a different chemical response: H2O2 converted sulfides to sulfoxides, while ClO− partially oxidized them further to sulfones. The different chemistry correlated to a different material response: H2O2 increased the polarity of the nanoparticles, causing them to swell in water and to release the surface PEGylated emulsifier; the uncoated oxidized particles still exhibited very low toxicity. On the contrary, ClO− rapidly converted the nanoparticles into water-soluble, depolymerized fragments with a significantly higher toxicity. The take-home message is that it is more correct to discuss ‘smart’ materials in terms of an environmentally specific response to (REDOX) stimuli. Far from being a problem, this could open the way to more sophisticated and precisely targeted applications.

A ROS-based Workspace Control and Trajectory Planner for a seven degrees of freedom Robotic arm

In this Bachelor Thesis I want to provide readers with tools and scripts for the control of a 7DOF manipulator, backed up by some theory of Robotics and Computer Science, in order to better contextualize the work done. In practice, we will see most common software, and developing environments, used to cope with our task: these include ROS, along with visual simulation by VREP and RVIZ, and an almost "stand-alone" ROS extension called MoveIt!, a very complete programming interface for trajectory planning and obstacle avoidance. As we will better appreciate and understand in the introduction chapter, the capability of detecting collision objects through a camera sensor, and re-plan to the desired end-effector pose, are not enough. In fact, this work is implemented in a more complex system, where recognition of particular objects is needed. Through a package of ROS and customized scripts, a detailed procedure will be provided on how to distinguish a particular object, retrieve its reference frame with respect to a known one, and then allow navigation to that target. Together with technical details, the aim is also to report working scripts and a specific appendix (A) you can refer to, if desiring to put things together.

Interspecific correlation between red blood cell mitochondrial ROS production, cardiolipin content and longevity in birds

This work was supported by the Swiss National Science Foundation (31003A-124988/1 to PB, 31003A-138187 and 31003A-159600/1 to PC). We are grateful to the staff of La Vaux-Lierre for giving us access to the bird care centre, to Sylvie Massemin and Jean-Patrice Robin for their help in data sampling and to Olivier Glaizot and two anonymous reviewers for their comments on the manuscript.

NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML

In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation including the promotion of leukemic cell proliferation and migration, as well as DNA-damage and accumulation of mutations. Work reviewed in this article has shown the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FLT3-ITD, an important oncoprotein in a subset of AML, causes activation of AKT and subsequently stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restored DEP-1 activity and attenuated cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy.

Una propuesta de enseñanza de kayakismo para navegar en aguas abiertas, mar y ríos de montaña

Esta ponencia tiene como objetivo compartir el trabajo realizado durante los últimos cuatro años en un curso de kayak que funciona en la ciudad de Berisso. En él se trabaja para desarrollar en los alumnos las habilidades motrices necesarias para poder navegar en el mar, ríos de montaña, aguas abiertas y saltar cascadas. En la primera parte se describirán a grandes rasgos las características de la propuesta, el contexto donde se desarrolla, los destinatarios, el lugar donde funciona, equipo docente, organización de los grupos y los recursos materiales utilizados. Luego nos introduciremos de lleno en la planificación y su organización. Analizaremos los objetivos, los contenidos y su organización en niveles, las actividades y viajes que se realizan para que los alumnos apliquen las habilidades motrices desarrolladas en el curso. Para finalizar realizaremos un análisis a partir de la propia experiencia sobre la complejidad de la enseñanza y del aprendizaje de la técnica del roll, las estrategias didácticas utilizadas, la importancia de trabajar la tranquilidad debajo del agua y por último cerraremos hablando de la evaluación en el curso de kayak en pileta

Una propuesta de enseñanza de kayakismo para navegar en aguas abiertas, mar y ríos de montaña

Esta ponencia tiene como objetivo compartir el trabajo realizado durante los últimos cuatro años en un curso de kayak que funciona en la ciudad de Berisso. En él se trabaja para desarrollar en los alumnos las habilidades motrices necesarias para poder navegar en el mar, ríos de montaña, aguas abiertas y saltar cascadas. En la primera parte se describirán a grandes rasgos las características de la propuesta, el contexto donde se desarrolla, los destinatarios, el lugar donde funciona, equipo docente, organización de los grupos y los recursos materiales utilizados. Luego nos introduciremos de lleno en la planificación y su organización. Analizaremos los objetivos, los contenidos y su organización en niveles, las actividades y viajes que se realizan para que los alumnos apliquen las habilidades motrices desarrolladas en el curso. Para finalizar realizaremos un análisis a partir de la propia experiencia sobre la complejidad de la enseñanza y del aprendizaje de la técnica del roll, las estrategias didácticas utilizadas, la importancia de trabajar la tranquilidad debajo del agua y por último cerraremos hablando de la evaluación en el curso de kayak en pileta

Una propuesta de enseñanza de kayakismo para navegar en aguas abiertas, mar y ríos de montaña

Esta ponencia tiene como objetivo compartir el trabajo realizado durante los últimos cuatro años en un curso de kayak que funciona en la ciudad de Berisso. En él se trabaja para desarrollar en los alumnos las habilidades motrices necesarias para poder navegar en el mar, ríos de montaña, aguas abiertas y saltar cascadas. En la primera parte se describirán a grandes rasgos las características de la propuesta, el contexto donde se desarrolla, los destinatarios, el lugar donde funciona, equipo docente, organización de los grupos y los recursos materiales utilizados. Luego nos introduciremos de lleno en la planificación y su organización. Analizaremos los objetivos, los contenidos y su organización en niveles, las actividades y viajes que se realizan para que los alumnos apliquen las habilidades motrices desarrolladas en el curso. Para finalizar realizaremos un análisis a partir de la propia experiencia sobre la complejidad de la enseñanza y del aprendizaje de la técnica del roll, las estrategias didácticas utilizadas, la importancia de trabajar la tranquilidad debajo del agua y por último cerraremos hablando de la evaluación en el curso de kayak en pileta

"Éros" y poesía en "Fedro", "Banquete" y "República": la reelaboración platónica de los terrenos poéticos para la realidad y el deseo

El trabajo explica el vínculo existente entre las distintas concepciones platónicas del éros y de la poesía, como parte del legado poético del siglo v. Y analiza su evolución, y la de su relación con la filosofía, en Fedro, Banquete y República, como un proceso de destilación del éros elaborado por la poesía, del que es afín el éros filosófico configurado en el Fedro, pero cuya incompatibilidad, insinuada en el Banquete, se hace explícita y taxativa en la República. Todo ello con el fin de demostrar hasta qué punto asume el pensamiento de Platón la herencia poética precedente, poniendo en evidencia que dicho proceso responde, en todas sus fases, a un mismo objetivo: materializar el anhelo poético por excelencia: la creación de un «terreno intermedio» donde conciliar la irrenunciable dualidad de las aspiraciones humanas. En consecuencia, se invita aquí a mirar la ciudad platónica como materialización posible, no utópica, de un espacio logrado en el que integrar armónicamente la realidad y el deseo.