Transactivation of Sphingosine-1–Phosphate Receptors by FcɛRI Triggering Is Required for Normal Mast Cell Degranulation and Chemotaxis

Mast cells secrete various substances that initiate and perpetuate allergic responses. Cross-linking of the high-affinity receptor for IgE (FcɛRI) in RBL-2H3 and bone marrow–derived mast cells activates sphingosine kinase (SphK), which leads to generation and secretion of the potent sphingolipid mediator, sphingosine-1–phosphate (S1P). In turn, S1P activates its receptors S1P1 and S1P2 that are present in mast cells. Moreover, inhibition of SphK blocks FcɛRI-mediated internalization of these receptors and markedly reduces degranulation and chemotaxis. Although transactivation of S1P1 and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcɛRI-triggered degranulation. However, S1P2, whose expression is up-regulated by FcɛRI cross-linking, was required for degranulation and inhibited migration toward antigen. Together, our results suggest that activation of SphKs and consequently S1PRs by FcɛRI triggering plays a crucial role in mast cell functions and might be involved in the movement of mast cells to sites of inflammation

Negative Regulation of Immunoglobulin E–dependent Allergic Responses by Lyn Kinase

A role for Lyn kinase as a positive regulator of immunoglobulin (Ig)E-dependent allergy has long been accepted. Contrary to this belief, Lyn kinase was found to have an important role as a negative regulator of the allergic response. This became apparent from the hyperresponsive degranulation of lyn−/− bone marrow–derived mast cells, which is driven by hyperactivation of Fyn kinase that occurs, in part, through the loss of negative regulation by COOH-terminal Src kinase (Csk) and the adaptor, Csk-binding protein. This phenotype is recapitulated in vivo as young lyn−/− mice showed an enhanced anaphylactic response. In vivo studies also demonstrated that as lyn−/− mice aged, their serum IgE increased as well as occupancy of the high affinity IgE receptor (FcεRI). This was mirrored by increased circulating histamine, increased mast cell numbers, increased cell surface expression of the high affinity IgE receptor (FcεRI), and eosinophilia. The increased IgE production was not a consequence of increased Fyn kinase activity in lyn−/− mice because both lyn−/− and lyn−/− fyn−/− mice showed high IgE levels. Thus, lyn−/− mice and mast cells thereof show multiple allergy-associated traits, causing reconsideration of the possible efficacy in therapeutic targeting of Lyn in allergic disease

Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells

Mast cell degranulation and de novo cytokine production is a consequence of antigen-aggregation of the immunoglobulin E (IgE)-occupied high affinity receptor for IgE (FcɛRI). Herein, we report that lymphokines that promote allergic inflammation, like MCP-1, were potently induced at low antigen (Ag) concentrations or at low receptor occupancy with IgE whereas some that down-regulate this response, like interleukin (IL)-10, required high receptor occupancy. Weak stimulation of mast cells caused minimal degranulation whereas a half-maximal secretory response was observed for chemokines and, with the exception of TNF-α, a weaker cytokine secretory response was observed. The medium from weakly stimulated mast cells elicited a monocyte/macrophage chemotactic response similar to that observed at high receptor occupancy. Weak stimulation also favored the phosphorylation of Gab2 and p38MAPK, while LAT and ERK2 phosphorylation was induced by a stronger stimulus. Gab2-deficient mast cells were severely impaired in chemokine mRNA induction whereas LAT-deficient mast cells showed a more pronounced defect in cytokines. These findings demonstrate that perturbation of small numbers of IgE receptors on mast cells favors certain signals that contribute to a lymphokine response that can mediate allergic inflammation

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion

Uso de e-mental health para el seguimiento posterapia de pacientes con depresión en Colombia

ABSTARCT: Use of E-Mental Health for monitoring depressive patients in Colombia Depressive disorders affect people of all ages, they reduce the quality of life and are recurrent. The most recent reports of the Ministry of Health and Social Protection establish between 12,1 and 13,1 % the prevalence of depression in the Colombian population. In recent years, the field of e-mental health has expanded rapidly and interventions based on communication and information technologies are being suggested as means to complement conventional mental health services. In this context, the research had as purpose to evaluate in Colombia the feasibility and acceptability of the technological intervention called “Apoyo, Seguimiento y Control de Enfermedades a partir de Sistemas Operativos –ASCENSO”. A purposive sample of patients discharged from psychotherapeutic treatments was selected. The HPQ-9 was applied, the ASCENSO platform was implemented, and finally, semi-structured interviews were conducted with study participants. The results show a favorable opinion of the patients that participated, the difficulties of the mental health institutions to join a project like this and a sensible lack of e-mental health programs in Colombia.RESUMEN: Los trastornos depresivos afectan a personas de todas las edades, reducen la calidad de vida y son recurrentes. Los informes más recientes del Ministerio de Salud y Protección Social establecen entre 12,1 y 13,1 % la prevalencia de la depresión en la población colombiana. En los últimos años, el campo del e-mental health se ha expandido rápidamente y las intervenciones basadas en las tecnologías de información y comunicación (TIC) se sugieren cada vez más como medio para complementar la atención convencional de la salud mental. En este contexto, la investigación tuvo como propósito evaluar en Colombia la factibilidad de uso y aceptabilidad de la estrategia de intervención tecnológica “Apoyo, Seguimiento y Control de Enfermedades a partir de Sistemas Operativos – ASCENSO”. Fue seleccionada una muestra intencional de pacientes dados de alta de tratamientos psicoterapéuticos. Se aplicó el HPQ-9, se implementó la plataforma ASCENSO y se realizaron entrevistas semiestructuradas a los participantes. Los resultados señalan la opinión favorable que manifestaron los pacientes que se beneficiaron del proceso, las dificultades de las instituciones de salud mental para vincularse a estos proyectos y una sensible ausencia de programas e-mental health en Colombia

Transdisciplinary studies in socio-ecosystems: Theoretical considerations and its application in Latin American contexts

Debido a limitaciones para abordar la complejidad de la relación sociedad-naturaleza, los esfuerzos para solucionar los problemas ambientales han sido en general infructuosos. Aquí proponemos que el enfoque holístico de “socio-ecosistema” por parte de la academia, podría contribuir a disminuir estas limitaciones desde la adopción de cuatro cambios: i) ontológico, que presenta el concepto de “socio-ecosistemas”; ii) epistemológico, que propone a la transdisciplina como la forma de entenderlos, iii) metodológico, que sugiere intervenir en ellos de forma participativa y adaptativa y, iv) cambios institucionales que facilitarían la adopción de esta propuesta. Este planteamiento se complementa con la descripción de una experiencia transdiciplinaria en la cuenca del río San Juan Zitácuaro, México, en el contexto de un curso internacional de manejo de socio-ecosistemas.Given the difficulties to approach the complex relationship bettween society and nature, efforts to solve environmental problems have generally been unsuccessful. Here we suggest that a hollistic “socio-ecosystem” approach by the sciencies could help diminish these difficulties by embracing four kinds of changes: i) ontological, which introduces the concept of “socio-ecosystem”; ii) epistemological, which proposes transdiscipline as the way to understand them, iii) metholodogical, which suggests that in intervention in them must be participatory and adaptive, iv) institutional changes that would facilitate the adoption of this approach. This is then followed by a description of a transdisciplinary work experience in the Zitácuaro river basin, in Mexico, in the context of an international course on socio-ecosystem management.Fil: Ortega Uribe, Tamara. Universidad de Chile; ChileFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Villarroel Torrez, Daniel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piaz, Agustín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica ; ArgentinaFil: Vallejos, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Saenz Ceja, Jesús Eduardo. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Gallego, Federico. Universidad de la República. Facultad de Ciencias; UruguayFil: Franquesa Soler, Monserrat. Instituto de Ecología; MéxicoFil: Calzada Peña, Leonardo. Universidad Nacional Autónoma de México; MéxicoFil: Espinosa Mellado, Noelia. Universidad de la Armada; MéxicoFil: Fiestas Flores, Jerico. Instituto de Estudios Peruanos; PerúFil: Gill Mairhofer, Luis R.. Ministerio de la Defensa Pública; ParaguayFil: González Espino, Zarahí. Instituto Superior de Tecnologías y Ciencias Aplicadas. Facultad de Medio Ambiente. Departamento de Meteorología; CubaFil: Luna Salguero, Betsabé Montserrat. Sociedad de Historia Natural Niparajá; MéxicoFil: Martinez Peralta, Claudia María. Comisión de Ecología y Desarrollo Sustentable del Estado de Sonora. Dirección General de Conservación; MéxicoFil: Ochoa, Olivia. Universidad Nacional Autónoma de México; MéxicoFil: Pérez Volkow,Lucía. No especifica;Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Sánchez Rose, Isabelle. Universidad Central de Venezuela; VenezuelaFil: Weeks, Madeline. University of Cambridge; Reino UnidoFil: Ávila García, Daniela. Universidad Nacional Autónoma de México; MéxicoFil: García Reyes, Isabel Bueno. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Carmona, Alejandra. Universidad Austral de Chile. Instituto de Economía Agraria; ChileFil: Castro Videla, Fernando Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan; ArgentinaFil: Ferrer Gonzalez, César Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Frank Buss, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: López Carapia, Gabriela. Universidad Nacional Autónoma de México; MéxicoFil: Núñez Cruz, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Taboada Hermoza, Rossi. Universidad Nacional Mayor de San Marcos; PerúFil: Benet, Daniel. Alternare A. C.; MéxicoFil: Venegas, Ysmael. Alternare A. C.; MéxicoFil: Balvanera, Patricia. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Mwampamba, Tuyeni H.. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Lazos Chavero, Elena. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Noellemeyer, Elke Johanna. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maass, Manuel. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; Méxic

Lepton Flavour Violation in Models with A4 Flavour Symmetry

We analyze lepton flavour violating transitions, leptonic magnetic dipole moments (MDMs) and electric dipole moments (EDMs) in a class of models characterized by the flavour symmetry A4 x Z3 x U(1)_{FN}, whose choice is motivated by the approximate tri-bimaximal mixing observed in neutrino oscillations. We construct the relevant low-energy effective Lagrangian where these effects are dominated by dimension six operators, suppressed by the scale M of new physics. All the flavour breaking effects are universally described by the vacuum expectation values of a set of spurions. We separately analyze both a supersymmetric and a general case. While the observed discrepancy delta a_mu in the anomalous MDM of the muon suggests M of order of a few TeV, several data require M above 10 TeV, in particular the limit on EDM of the electron. In the general case also the present limit on BR(mu -> e gamma) requires M >10 TeV, at least. The branching ratios for mu -> e gamma, tau -> mu gamma and tau -> e gamma are all expected to be of the same order. In the supersymmetric case the constraint from mu -> e gamma is softened and it can be satisfied by a smaller scale M. In this case both the observed delta a_mu and the current bound on BR(mu -> e gamma) can be satisfied, at the price of a rather small value for ||, of the order of a few percents, that reflects on a similar value for theta_{13}.Comment: 29 pages, 1 figur

Being oneself through time: bases of self-continuity across 55 cultures

Self-continuity – the sense that one’s past, present, and future are meaningfully connected – is considered a defining feature of personal identity. However, bases of self-continuity may depend on cultural beliefs about personhood. In multilevel analyses of data from 7287 adults from 55 cultural groups in 33 nations, we tested a new tripartite theoretical model of bases of self-continuity. As expected, perceptions of stability, sense of narrative, and associative links to one’s past each contributed to predicting the extent to which people derived a sense of self-continuity from different aspects of their identities. Ways of constructing self-continuity were moderated by cultural and individual differences in mutable (vs. immutable) personhood beliefs – the belief that human attributes are malleable. Individuals with lower mutability beliefs based self-continuity more on stability; members of cultures where mutability beliefs were higher based self-continuity more on narrative. Bases of self-continuity were also moderated by cultural variation in contextualized (vs. decontextualized) personhood beliefs, indicating a link to cultural individualism-collectivism. Our results illustrate the cultural flexibility of the motive for self-continuity

TERAPÊUTICA NÃO MEDICAMENTOSA PARA DOR CRÔNICA: REVISÃO INTEGRATIVA

A dor é um mecanismo desagradável, que o corpo humano experimenta quando há um dano tecidual, funcionando para alerta e defesa. No Brasil, há poucos estudos epidemiológicos sobre dor crônica, mas há pesquisas que mostram que, em média, 35% da população é portadora de dor crônica. Assim, a presente pesquisa objetiva revisar, na literatura científica, as principais formas de tratamento não medicamentoso para dor crônica. O presente estudo consiste em uma revisão bibliográfica integrativa da literatura científica, através dos seguintes Descritores em Ciências da Saúde: “Dor Crônica”, “Fisioterapia/Acupuntura”, “Integralidade em Saúde”, nas bases de dados científicos Scientific Electronic Library Online (SCIELO), biblioteca virtual em saúde (BVS) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Estudos demonstram que, a partir das atividades de alongamento e relaxamento, propostas pela fisioterapeuta e pelo educador físico, há uma redução da demanda por medicamentos analgésicos e anti-inflamatórios, além da diminuição de procura por consultas, para atendimento da referida queixa.A dor é um mecanismo desagradável, que o corpo humano experimenta quando há um dano tecidual, funcionando para alerta e defesa. No Brasil, há poucos estudos epidemiológicos sobre dor crônica, mas há pesquisas que mostram que, em média, 35% da população é portadora de dor crônica. Assim, a presente pesquisa objetiva revisar, na literatura científica, as principais formas de tratamento não medicamentoso para dor crônica. O presente estudo consiste em uma revisão bibliográfica integrativa da literatura científica, através dos seguintes Descritores em Ciências da Saúde: “Dor Crônica”, “Fisioterapia/Acupuntura”, “Integralidade em Saúde”, nas bases de dados científicos Scientific Electronic Library Online (SCIELO), biblioteca virtual em saúde (BVS) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Estudos demonstram que, a partir das atividades de alongamento e relaxamento, propostas pela fisioterapeuta e pelo educador físico, há uma redução da demanda por medicamentos analgésicos e anti-inflamatórios, além da diminuição de procura por consultas, para atendimento da referida queixa