Appropriate maintenance treatment for Crohn's disease: results of a multidisciplinary international expert panel - EPACT II

Introduction: Biological. therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNF alpha inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNF alpha antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a "wait-and-see" strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNF alpha agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNF alpha agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Enraizamento de corticeira-da-serra em função do tipo de estaca e variações sazonais

Erythrina falcata Benth. tem sido usada na recuperação de ecossistemas degradados, como planta ornamental e em sistemas agroflorestais. Entretanto, a produção de mudas por sementes é difícil. O objetivo deste trabalho foi avaliar a propagação vegetativa de E. falcata utilizando estacas caulinares provenientes de árvores adultas (estacas herbáceas, semilenhosas e de rebrota) e mudas, coletadas em quatro épocas do ano e o efeito do ácido indolbutírico (AIB) no enraizamento de estacas dessa espécie. Depois de preparadas, as estacas foram imersas em ácido indolbutírico (AIB, 0, 1,5 e 3 g L-1). O material se desenvolveu em tubetes de plástico (55 mL), em casa de vegetação climatizada, a uma temperatura de 25 a 30ºC e umidade relativa do ar acima de 80%, em substrato de vermiculita granulometria média. Maior porcentagem de enraizamento (73%), comprimento das quatro maiores raízes (46 mm) e número de raízes (6,2) foram obtidos em estacas de mudas coletadas no verão. Não houve enraizamento em estacas semilenhosas, provenientes de árvores adultas. A imersão das estacas em AIB não exerceu qualquer influência no enraizamento. As estacas de mudas coletadas no verão são as de melhor propagação vegetativa em virtude de melhor porcentagem de enraizamento e sobrevivência.

Modelagem de funções no cálculo dos índices DRIS

O objetivo deste trabalho foi modelar o fator k e as funções DRIS para a diagnose foliar de mangueiras cultivadas. Dez pomares comerciais, no estágio de produção, localizados no vale do Rio São Francisco, foram monitorados, mensalmente, durante dois anos, por meio da coleta de amostras foliares para determinação dos teores de N, P, K, Ca, Mg, B, Fe, Mn, Zn e Cu. Os dados foram testados quanto à normalidade e as relações entre as concentrações dos nutrientes foram usadas para calcular as normas DRIS, obtendo-se média, variância e limites máximo e mínimo de cada relação dentro da população amostrada. Os nutrientes foram classificados como macronutrientes de resposta freqüente (MAF) (N, P e K), macronutrientes de resposta rara (MAR) (Ca e Mg); micronutrientes de resposta freqüente (MIF) (B, Fe, Mn e Zn) e, micronutrientes de resposta rara (MIR) (Cu). Funções DRIS foram desenvolvidas para cada classe de nutrientes. O modelo desenvolvido expressa o balanço nutricional das plantas cultivadas ajustado a cada nutriente e reflete o comportamento biológico das plantas como resultado da variação da disponibilidade dos nutrientes.

Experiencia en gestión de redes sociales en el CRAI de la UB

El CRAI de la Universidad de Barcelona (CRAI UB) empezó a investigar y a utilizar las redes sociales entre finales del 2006 y principios del 2007. En aquellos momentos los blogs fueron las primeras redes que en las que participamos. El hecho de permitir comunicarnos con los usuarios a través de noticias de interés y de recibir sus comentarios hizo que los blogs fueran un medio dinámico en contraste con las tradicionales páginas web estáticas. El primer blog que elaboramos fue el del CRAI Biblioteca de Letras. Lentamente y en función de su viabilidad se impulsó, desde la unidad transversal de Proyectos del CRAI UB, la presencia del resto de CRAI Bibliotecas en las redes sociales. Con la aparición de Facebook se abrió una nueva posibilidad de comunicación e interactividad con los usuarios potenciales del CRAI UB, que se vio favorecida también con la irrupción de Twitter. En un principio, se empezaron a crear cuentas con perfiles personales y, cuando fue posible, pasaron a ser cuentas institucionales. Si hablamos de un público universitario como el nuestro, es Facebook la que arrastra mayor audiencia y, por consiguiente, la que permite llegar a un mayor número de usuarios. Esta posibilidad de compartir información de forma inmediata y sin demasiado esfuerzo añadido fue el impulso definitivo a la generalización de las redes sociales en la mayoría de los CRAI Bibliotecas.

El moviment d'objecció de consciència i insubmissió al servei militar a Reus

La Història ha estat formalment el meu itinerari dins l’infinit univers de les Humanitats.Crec convençudament que l’anàlisi sincer i la reflexió profunda sobre el passat ens ajuden acomprendre el gènere humà i alhora ens aporten llum sobre com actuar en les situacionspresents. És per això que d’entrada volia escollir un tema d’Història Contemporània pelmeu treball. Contemporània per tal de que el tema pogués ser relacionat més directamentamb el món en crisi que ens envolta i que tant em preocupa. Volia, per tant, que el meutreball tingués un cert grau de compromís social, que no fos un mer aprofundimentacadèmic reclòs en el món de les idees, sinó que pogués tenir alguna repercussió en lareflexió que s’està duent a terme respecte els vertiginosos canvis socials que estem vivint iles injustícies que existeixen en l’actual sistema.

Valproate treatment of human cord blood CD4-positive effector T cells confers on them the molecular profile (microRNA signature and FOXP3 expression) of natural regulatory CD4-positive cells through inhibition of histone deacetylase.

Regulatory T cells (Tregs) play a key role in immune system homeostasis and tolerance to antigens, thereby preventing autoimmunity, and may be partly responsible for the lack of an appropriate immune response against tumor cells. Although not sufficient, a high expression of forkhead box P3 (FOXP3) is necessary for their suppressive function. Recent reports have shown that histones deacetylase inhibitors increased FOXP3 expression in T cells. We therefore decided to investigate in non-Tregs CD4-positive cells, the mechanisms by which an aspecific opening of the chromatin could lead to an increased FOXP3 expression. We focused on binding of potentially activating transcription factors to the promoter region of FOXP3 and on modifications in the five miRs constituting the Tregs signature. Valproate treatment induced binding of Ets-1 and Ets-2 to the FOXP3 promoter and acted positively on its expression, by increasing the acetylation of histone H4 lysines. Valproate treatment also induced the acquisition of the miRs Tregs signature. To elucidate whether the changes in the miRs expression could be due to the increased FOXP3 expression, we transduced these non-Tregs with a FOXP3 lentiviral expression vector, and found no changes in miRs expression. Therefore, the modification in their miRs expression profile is not due to an increased expression of FOXP3 but directly results from histones deacetylase inhibition. Rather, the increased FOXP3 expression results from the additive effects of Ets factors binding and the change in expression level of miR-21 and miR-31. We conclude that valproate treatment of human non-Tregs confers on them a molecular profile similar to that of their regulatory counterpart.

Genomics of host-pathogen interactions.

The study of immunity against infection can be framed in the context of genomics. First, long-term association with pathogens results in genomic signatures that result from positive selection. Evolutionary pressures tailor species or individual responses to pathogens, that may be associated with skewed patterns of immunity. Second, recent human population expansion carries an increasing burden of genetic mutation that can result in sporadic immunodeficiencies, and more generally, in diversity in susceptibility to infection. This review highlights current concepts and tools for the analysis of genomes and stresses the interest of these approaches in immunity.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.

Luz, substrato e temperatura na germinação de sementes de cedro-vermelho

O objetivo deste estudo foi avaliar o tipo de substrato, a temperatura e os regimes de luz mais adequados à germinação de sementes de Cedrela odorata L. O delineamento experimental adotado, em todos os ensaios, foi o inteiramente casualizado com quatro repetições de 25 sementes cada. As temperaturas constantes de 25 e 30ºC, a temperatura alternada de 20-30ºC e os substratos pó de coco e areia são as melhores condições para a germinação das sementes de C. odorata. A germinação das sementes da espécie estudada não se mostrou sensível aos diferentes regimes de luz aplicados.

Solubilização do fosfato de ferro em meio de cultura

O objetivo deste trabalho foi avaliar a eficiência de solubilização de FePO4 por Aspergillus niger, em meio de cultura com diferentes fontes de carbono (C) e nitrogênio (N) e com concentrações crescentes de fosfato. A quantidade de fosfato solúvel, acidez e pH final foram determinados após o crescimento do fungo, em cultura estacionária a 30ºC. A eficiência de solubilização aumentou conforme o crescimento do fungo, atingiu o máximo no 11º dia (68%) e depois regrediu. Das fontes de C e de N testadas, as maiores eficiências de solubilização foram obtidas com manitol (21%) e ácido glutâmico (17%). Com o aumento da concentração de fosfato (0 a 1.330 µg mL-1), a máxima eficiência de solubilização (70%) foi obtida com 330 µg mL-1 de PO4(3-) e decresceu até 47% com 1.330 µg mL-1. A produção de ácidos foi o principal mecanismo de solubilização do FePO4, com base na correlação positiva e significativa entre a produção de fosfato e a acidez.

Crescimento micelial de Pleurotus ostreatus em resíduo de Simarouba amara

O objetivo deste trabalho foi avaliar o crescimento micelial do cogumelo Pleurotus ostreatus, cultivado na serragem da espécie madeireira Simarouba amara. Avaliaram-se: o efeito das temperaturas de 22, 25, 27, 30 e 35ºC sobre o crescimento micelial de P. ostreatus, nos meios malte-ágar 3% e SDA-MA (infusão da serragem de S. amara, enriquecida com farelo de soja-dextrose-ágar); e o crescimento micelial em substrato de cultivo de serragem de S. amara, com e sem suplementação de farelo de soja, a 25 e 30ºC. O melhor desenvolvimento de P. ostreatus ocorreu em meio malte-ágar 3% a 25ºC. A suplementação de farelo de soja na serragem de S. amara favorece o crescimento micelial.

Qualidade de goiaba-serrana em resposta à temperatura de armazenamento e ao tratamento com 1-metilciclopropeno

Os objetivos deste trabalho foram caracterizar a fisiologia e avaliar os efeitos da temperatura e da aplicação de 1-metilciclopropeno (1-MCP) na qualidade pós-colheita de frutos de goiaba-serrana (Acca selowiana), em acessos do banco ativo de germoplasma da Empresa de Pesquisa Agropecuária e Extensão Rural de Santa Catarina. Os frutos foram colhidos na maturação comercial. Os genótipos Brasil (acesso 387) e Uruguai (acesso 454) foram avaliados quanto ao comportamento respiratório e de produção de etileno a 20ºC, e taxas respiratórias e alterações na cor da casca a 0, 5, 10, 20 e 30ºC. O genótipo Brasil (acesso 242) foi avaliado quanto ao amadurecimento a 4ºC, após tratamento com 1-MCP (0, 500 e 1.500 ppb). Os genótipos Brasil (acesso 387) e Uruguai (acesso 454) apresentaram comportamento climatérico, com picos de produção de etileno e de taxa respiratória aos 8 e 12 dias de armazenamento a 20ºC, respectivamente. Não houve diferença significativa entre as taxas respiratórias e de produção de etileno entre os genótipos, nessa temperatura. Houve aumento substancial na taxa respiratória em ambos os genótipos, com o aumento de 0 para 30ºC, com coeficiente metabólico de 3,5 aproximadamente. Com o aumento na temperatura, houve maior alteração na cor verde da epiderme, em frutos do tipo Brasil, e maior escurecimento da epiderme, em frutos do tipo Uruguai. Frutos do genótipo Brasil (acesso 242), tratados com 1-MCP e armazenados a 4ºC, apresentaram retardamento no amadurecimento.