324 research outputs found

    Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

    Get PDF
    Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling

    CUIDADO E CONFORTO NO PARTO: ESTUDOS NA ENFERMAGEM BRASILEIRA

    Get PDF
     Estudo de revisão teórica acerca dos artigos brasileiros de enfermagem sobre o cuidado e conforto durante o trabalho de parto e parto, com o objetivo de identificar os estudos de Enfermagem que abordam este tema, buscando destacar lacunas existentes na área. A busca em bases de dados Bireme e Portal de Revistas de Enfermagem por intermédio dos descritores Parto, Trabalho de Parto e Período Pós-Parto e dos títulos e resumos relacionados ao tema, delimitados ao período de 2000 a 2008, possibilitou a  identificação de 24 artigos. Para análise dos dados, foram estabelecidas as seguintes categorias:  Medicalização do Processo de Parto, Humanização dos Cuidados, Papel da Equipe de Saúde, Violência, Dor, Presença de Acompanhante e Cuidado e Conforto. Os resultados indicam a necessidade de estudos sob a perspectiva das mulheres que vivenciam o parto, a fim de aprimorar os cuidados a elas prestados. Concluiu-se que é necessário aprofundar o conhecimento a respeito do cuidado e do conforto prestados no processo do parto a partir da percepção de quem vivencia esse momento.

    Cuidado de enfermagem à puérpera no domicílio na perspectiva do modelo de cuidado de carraro

    Get PDF
    Aim: to present the journeys of the nursing home-care for women during immediate and later post-partum periods given the perspective of the Carraro Care Model. Methodology: convergent-care study developed in the town of Corbélia – Paraná, from April to June 2011. Results: care strategies directed to a single care and towards unique human beings emerged. Therefore, caution, flexibility, interest and to act reflexibly with the woman are important matters to exercise nursing in a way that values its science and art. Conclusion: with Carraro Care Model, it is possible to awake the Vital Power of postpartum women and their families for a dynamic care, that values the biographical relational context, where the internal and external environment are linked to interpersonal relationships.Objetivo: presentar trayectos para que la enfermera cuide de la mujer en domicilio durante el puerperio inmediato y tardío, en la perspectiva del Modelo de Cuidado de Carraro. Metodología: investigación convergente-asistencial, desarrollada en la ciudad de Corbélia - Paraná, entre abril y junio de 2011. Resultados: surgieron estrategias de cuidado que orientan al cuidado único a un ser que también es único, siendo necesario cautela, flexibilidad, demostración de interés y actuación de manera reflexiva, para que el ejercicio de la enfermería ocurra de modo a que se valoren su ciencia y su arte. Conclusión: con la aplicación del Modelo de Cuidado de Carraro es posible despertar el Poder Vital de puérperas y sus familias a un cuidado dinámico que valora el contexto biográfico relacional, donde el medio interno y externo están vinculados a las relaciones interpersonales.Objetivo: apresentar trajetos para a enfermeira cuidar da mulher no domicílio durante o puerpério imediato e tardio na perspectiva do Modelo de Cuidado de Carraro. Metodologia: pesquisa Convergente-Assistencial, desenvolvida no município de Corbélia – Paraná, entre abril e junho de 2011. Resultados: emergiram estratégias de cuidado direcionando a um cuidar único para um ser humano também único, sendo necessário existir cautela, flexibilidade, demonstrar interesse, agir de maneira reflexiva junto à mulher, exercendo a enfermagem de modo a valorizar sua ciência e arte. Conclusão: utilizando-se do Modelo de Cuidado de Carraro é possível despertar o Poder Vital da puérpera e de seus familiares para um cuidado dinâmico, que valoriza o contexto biográfico relacional, onde o meio externo e interno estão vinculados às relações interpessoais

    ENSEÑAR-APRENDER A CUIDAR DE HERIDAS: EXPERIENCIA DE ENFERMERAS EN PRÁCTICAS DOCENTES

    Get PDF
    A realização de estágio docência é um quesito instituído para bolsistas da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior e Conselho Nacional de Desenvolvimento Científico e Tecnológico. Este texto objetiva narrar a experiência de ensinar-aprender a cuidar de feridas, vivenciada por quatro pós-graduandas de enfermagem durante a realização de seus estágios docência, em uma instituição pública de ensino superior do sul do Brasil. O estágio ocorreu de agosto a dezembro de 2010 e foi desenvolvido na disciplina de Fundamentos para o Cuidado Profissional do curso de Graduação em Enfermagem da mesma universidade. Considerou-se como um momento importante de aprendizagem nos contextos tutoria em sala de aula, prática em laboratório de enfermagem e em hospital onde o ensinar e aprender estiveram intimamente relacionados. A experiência proporcionou a ampliação dos olhares para a formação em enfermagem.La realización de prácticas de docencia es un requisito instituido para becarios de la Coordinación de Perfeccionamiento de Personal de Nivel Superior y Consejo Nacional de Desarrollo Científico y Tecnológico. Este texto objetiva narrar la experiencia de enseñar-aprender a cuidar de heridas, vivida por cuatro posgraduandas de enfermería durante la realización de sus prácticas de docencia, en una institución pública de enseñanza superior del sur de Brasil. Las prácticas ocurrieron de agosto a diciembre de 2010 y fueon desarrolladas en la disciplina de Fundamentos para el Cuidado Profesional del curso de Graduación en enfermería de la misma universidad. Se consideró un momento importante de aprendizaje en los contextos tutoría en aula de clase, práctica en laboratorio de enfermería y en hospital donde el enseñar y aprender estuvieron relacionados de modo íntimo. La experiencia ha proporcionado más atención para la formación en enfermería.The carrying out of a teaching placement is a requirement for scholarship students of the Coordination for Perfection of Higher Education Staff and the National Council for Scientific and Technological Development. This text aims to relate the experience of teaching-learning wound care, as experienced by four post-graduate students during their teaching placements, in a public higher education institution in the South of Brazil. The placement took place from August to December 2010 in the Basics of Professional Care course, part of the same university’s undergraduate nursing course. It was considered an important learning stage in the contexts tutorship in the classroom, and laboratory and hospital practice, where teaching and learning are very closely linked. The experience permitted a widening of understanding concerning nursing training

    Properties of the permeability transition of pea stem mitochondria

    Get PDF
    In striking analogy with Saccharomyces cerevisiae, etiolated pea stem mitochondria did not show appreciable Ca2+ uptake. Only treatment with the ionophore ETH129 (which allows electrophoretic Ca2+ equilibration) caused Ca2+ uptake followed by increased inner membrane permeability, membrane depolarization and Ca2+ release. Like the permeability transition (PT) of mammals, yeast and Drosophila, the PT of pea stem mitochondria was stimulated by diamide and phenylarsine oxide and inhibited by MgADP and Mg-ATP, suggesting a common underlying mechanism; yet, the plant PT also displayed distinctive features: (i) as in mammals it was desensitized by cyclosporin A, which does not affect the PT of yeast and Drosophila; (ii) similarly to S. cerevisiae and Drosophila it was inhibited by Pi, which stimulates the PT of mammals; (iii) like in mammals and Drosophila it was sensitized by benzodiazepine 423, which is ineffective in S. cerevisiae; (iv) like what observed in Drosophila it did not mediate swelling and cytochrome c release, which is instead seen in mammals and S. cerevisiae. We find that cyclophilin D, the mitochondrial receptor for cyclosporin A, is present in pea stem mitochondria. These results indicate that the plant PT has unique features and suggest that, as in Drosophila, it may provide pea stem mitochondria with a Ca2+ release channel

    A forgotten life-threatening medical emergency: myxedema coma

    Get PDF
    Nowadays myxedema coma is a rare medical emergency but, sometimes, it still remains a fatal condition even if appropriate therapy is soon administered. Although physical presentation is very non-specific and diversified, physicians should pay attention when patients present with low body temperature and alteration of neurological status; the presence of precipitating events in past medical history can help in making a diagnosis. Here we discuss one such case: an 83-year-old female presented with abdominal pain since few days. Laboratory tests and abdomen computed tomography scan demonstrated alithiasic cholecystitis; she was properly treated but, during the Emergency Department stay she experienced a cardiac arrest. Physicians immediately started advance cardiovascular life support algorithm and she survived. Later on, she was admitted to the Intensive Care Unit where doctors discovered she was affected by severe hypothyroidism. Straightway they started the right therapy but, unfortunately, the patient died in a few hours

    Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients

    Get PDF
    Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML
    corecore