Corticoides versus Placebo o tratamiento conservador en Cefalea post punción dural. Revisión sistemática y metaanálisis

Introducción Se realizó una revisión sistemática de la literatura y metaanálisis para determinar la utilidad, en términos de reducción de la intensidad y la prevención de la cefalea post-punción dural, de los corticoides endovenosos. Materiales y métodos Revisión sistemática y metaanálisis, dos revisores seleccionaron y analizaron los artículos definidos en los términos de entrada, extrajeron características generales de los estudios incluidos, describieron los principales hallazgos y resumieron sus resultados. Se analizó la heterogeneidad por el coeficiente de I2 y Tau2 , la magnitud del efecto se analizó en el coeficiente Z, todos los estadísticos asumieron un nivel de significancia del 95%, en cuadros y figuras (de control de sesgos y Forres Plot) Resultados 75 Referencias fueron seleccionadas, 33 identificadas en la búsqueda y 48 por método de Snowball; Seis concordaron con los criterios de elegibilidad; 69 fueron excluidas por no cumplir con los criterios de inclusión; el enmascaramiento aspecto de mayor riesgo de sesgo (intermedio); en conjunto hubo buen control del riesgo de sesgo entre los estudios incluidos. Los resultados muestran baja heterogeneidad a favor de la intervención con corticoides en el tratamiento de la cefalea post-dural; amplia heterogeneidad y sin efecto para la prevención de la cefalea post-dural. Conclusiones Se recomienda el uso de hidrocortisona o metilprednisolona en la reducción de la intensidad de la cefalea post-dural. No se cuenta con evidencia de dexametasona en la prevención de cefalea postdural. Se requiere de estudios adicionales, con otras intervenciones farmacológicas que sobre la plausibilidad de la condición (cefalea post-dural) pudieran prevenir o disminuir su ocurrencia

Desarrollo de métodos rápidos para el análisis de residuos en producción animal

La utilización de algunas sustancias antimicrobianas y algunos corticosteroides como promotores del crecimiento es una práctica ilegal en la UE. Una nueva aproximación para la detección y el control del suministro de estos compuestos puede ser el análisis del pelo. Esta matriz presenta ciertas ventajas frente a otras matrices de análisis, pero los métodos analíticos así como los principales mecanismos por los cuales estas sustancia se acumulan, no están del todo claros ni bien definidos. En este trabajo se desarrollan protocolos de análisis rápidos y específicos para detectar residuos de sulfametacina (SMZ), enrofloxacino (ENR) y dexametasona (DEX) en pelo, músculo e hígado de animales de producción (vacuno y porcino). Asimismo, se confirma la deposición de estos compuestos en el pelo de animales tratados y se evalúa el pelo como matriz analítica y de control de la administración de estos compuestos en producción animal.

Uso de metilprednisolona como tratamento adjuvante do choque hipovolémico, distributivo e séptico

Hoje em dia, o uso abusivo de corticosteroide nos vários tipos de choque(hipovolémico,distributivo e séptico) tem levado a debates polémicos. Ao comparar, os resultados dos inúmeros autores que abordaram este tema, não é possível tirar uma conclusão unânime. A opinião de cada um diverge, havendo autores que apoiam e outros que refutam a sua utilização no choque. O objetivo deste estudo consiste em verificar se o uso metilprednisolona vai surtir algum benefício na reversão e sobrevivência do choque, nos animais, em que a terapêutica inicial de abordagem ao choque não tenha surtido efeito. O presente estudo foi realizado no Hospital Veterinário da Arrábida (HVA), em Azeitão, ao longo de um período de 7 meses, decorrido entre 1 de Setembro de 2011 até 31 Março de 2012. Durante esse tempo, procedeu-se ao acompanhamento de 57 animais em choque hipovolémico, distributivo ou séptico. Nas primeiras horas após ser instituído a fluidoterapia de choque e vasopressores, existiram animais em estudo que não conseguiu estabilizar a pressão arterial média (PAM) dentro dos valores normais de referência. Nestes casos foi administrado um tratamento adjuvante com metilprednisolona. Através da análise descritiva da população em estudo verificou-se que a taxa de mortalidade foi menor no grupo de canídeos e felídeos em que não se efetuou o tratamento adjuvante com metilprednisolona.

Rastreio Serológico de Toxoplasmose em Gatos dos Concelhos de Oeiras e Cascais

A toxoplasmose é uma das parasitoses mais comuns em gatos sendo que a sua seroprevalência mundial varia entre 5,5% e 97,4%. Em Portugal, existem poucos estudos sobre a prevalência da toxoplasmose e, por isso, este estudo tem como objetivo principal contribuir para o conhecimento da seroprevalência de base clínica no nosso país. Para a sua realização, foram colhidas amostras de soro de 63 gatos e recolhidos dados epidemiológicos sobre a idade, a raça, o género, o tipo de alimentação, o acesso ao exterior e o tipo de habitat dos progenitores. As amostras de soro foram analisadas através da técnica de imunofluorescência indireta, tendo sido encontrados 25 gatos seropositivos, correspondendo a uma seroprevalência de base clínica de 41%. O único fator de risco identificado foi o acesso ao exterior. A idade do animal não foi estatisticamente significativa como fator de risco, mas observou-se um aumento da prevalência em animais até aos 6 anos de idade. Os gatos de progenitores com acesso ao exterior, animais de género feminino e com alimentação de risco apresentaram maior número de seropositivos, no entanto, estes resultados não foram estatisticamente significativos.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Inhalation exposure to particulate matter in rooms with underfloor air distribution

This work investigated the personal exposure to indoor particulate matters using the intake fraction metric and provided a possible way to trace the particle inhaled from an indoor particle source. A turbulence model validated by the particle measurements in a room with underfloor air distribution (UFAD) system was used to predict the indoor particle concentrations. Inhalation intake fraction of indoor particles was defined and evaluated in two rooms equipped with the UFAD, i.e., the experimental room and a small office. According to the exposure characteristics and a typical respiratory rate, the intake fraction was determined in two rooms with a continuous and episodic (human cough) source of particles, respectively. The findings showed that the well-mixing assumption of indoor air failed to give an accurate estimation of inhalation exposure and the average concentration at return outlet or within the overall room could not relate well the intake fraction to the amount of particle emitted from an indoor source.

Modeling the effects of anesthesia on the electroencephalogram

Changes to the electroencephalogram (EEG) observed during general anesthesia are modeled with a physiological mean field theory of electrocortical activity. To this end a parametrization of the postsynaptic impulse response is introduced which takes into account pharmacological effects of anesthetic agents on neuronal ligand-gated ionic channels. Parameter sets for this improved theory are then identified which respect known anatomical constraints and predict mean firing rates and power spectra typically encountered in human subjects. Through parallelized simulations of the eight nonlinear, two-dimensional partial differential equations on a grid representing an entire human cortex, it is demonstrated that linear approximations are sufficient for the prediction of a range of quantitative EEG variables. More than 70 000 plausible parameter sets are finally selected and subjected to a simulated induction with the stereotypical inhaled general anesthetic isoflurane. Thereby 86 parameter sets are identified that exhibit a strong “biphasic” rise in total power, a feature often observed in experiments. A sensitivity study suggests that this “biphasic” behavior is distinguishable even at low agent concentrations. Finally, our results are briefly compared with previous work by other groups and an outlook on future fits to experimental data is provided.

Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway

Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2. In wild-type mice, immunoreactive PAR2 was detected in airway epithelial cells and myocytes, and intranasal administration of a PAR2 agonist stimulated macrophage infiltration into bronchoalveolar lavage fluid. OVA challenge of immunized wild-type mice stimulated infiltration of leukocytes into bronchoalveolar lavage and induced airway hyperreactivity to inhaled methacholine. Compared with wild-type animals, eosinophil infiltration was inhibited by 73% in mice lacking PAR2 and increased by 88% in mice overexpressing PAR2. Similarly, compared with wild-type animals, airway hyperreactivity to inhaled methacholine (40 micro g/ml) was diminished 38% in mice lacking PAR2 and increased by 52% in mice overexpressing PAR2. PAR2 deletion also reduced IgE levels to OVA sensitization by 4-fold compared with those of wild-type animals. Thus, PAR2 contributes to the development of immunity and to allergic inflammation of the airway. Our results support the proposal that tryptase inhibitors and PAR2 antagonists may be useful therapies for inflammatory airway disease.

Drug permeability in 16HBE14o- airway cell layers correlates with absorption from the isolated perfused rat lung

The permeability of the lung is critical in determining the disposition of inhaled drugs and the respiratory epithelium provides the main physical barrier to drug absorption. The 16HBE14o- human bronchial epithelial cell line has been developed recently as a model of the airway epithelium. In this study, the transport of 10 low molecular weight compounds was measured in the 16HBE14o- cell layers, with apical to basolateral (absorptive) apparent permeability coefficients (P(app)) ranging from 0.4 x 10(-6)cms(-1) for Tyr-D-Arg-Phe-Phe-NH(2) to 25.2x10(-6)cms(-1) for metoprolol. Permeability in 16HBE14o- cells was found to correlate with previously reported P(app) in Caco-2 cells and absorption rates in the isolated perfused rat lung (k(a,lung)) and the rat lung in vivo (k(a,in vivo)). Log linear relationships were established between P(app) in 16HBE14o- cells and P(app) in Caco-2 cells (r(2)=0.82), k(a,lung) (r(2)=0.78) and k(a,in vivo) (r(2)=0.68). The findings suggest that permeability in 16HBE14o- cells may be useful to predict the permeability of compounds in the lung, although no advantage of using the organ-specific cell line 16HBE14o- compared to Caco-2 cells was found in this study.

Septic Shock, Necrotizing Pneumonitis, and Meningoencephalitis Caused by Mycoplasma pneumoniae in a Child: A Case Report

Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids

Anesthetic Activation of Central Respiratory Chemoreceptor Neurons Involves Inhibition of a THIK-1-Like Background K(+) Current

At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.

Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome

Ischemia and reperfusion injury (IRI) are mainly caused by leukocyte activation, endothelial dysfunction and production of reactive oxygen species. Moreover, IRI can lead to a systemic response affecting distant organs, such as the lungs. The objective was to study the pulmonary inflammatory systemic response after renal IRI. Male C57Bl/6 mice were subjected to 45 min of bilateral renal ischemia, followed by 4, 6, 12, 24 and 48 h of reperfusion. Blood was collected to measure serum creatinine and cytokine concentrations. Bronchoalveolar lavage fluid (BALF) was collected to determine the number of cells and PGE(2) concentration. Expressions of iNOS and COX-2 in lung were determined by Western blot. Gene analyses were quantified by real time PCR. Serum creatinine increased in the IRI group compared to sham mainly at 24 h after IRI (2.57 +/- A 0.16 vs. 0.43 +/- A 0.07, p < 0.01). The total number of cells in BAL fluid was higher in the IRI group in comparison with sham, 12 h (100 x 10(4) +/- A 15.63 vs. 18.1x10(4) +/- A 10.5, p < 0.05) 24 h (124 x 10(4) +/- A 8.94 vs. 23.2x10(4) +/- A 3.5, p < 0.05) and 48 h (79 x 10(4) +/- A 15.72 vs. 22.2 x 10(4) +/- A 4.2, p < 0.05), mainly by mononuclear cells and neutrophils. Pulmonary COX-2 and iNOS were up-regulated in the IRI group. TNF-alpha, IL-1 beta, MCP-1, KC and IL-6 mRNA expression were up-regulated in kidney and lungs 24 h after renal IRI. ICAM-1 mRNA was up-regulated in lungs 24 h after renal IRI. Serum TNF-alpha, IL-1 beta and MCP-1 and BALF PGE(2) concentrations were increased 24 h after renal IRI. Renal IRI induces an increase of cellular infiltration, up-regulation of COX-2, iNOS and ICAM-1, enhanced chemokine expression and a Th1 cytokine profile in lung demonstrating that the inflammatory response is indeed systemic, possibly leading to an amplification of renal injury.

The role of glucocorticoid in SIRP alpha and SHP-1 gene expression in AIHA patients

The aim of this work was to evaluate the regulation of SIRP alpha, an inhibitory phagocyte receptor, and the phosphatase SHP-1 in monocytes of patients with autoimmune hemolytic anemia, and the role of dexamethasone on SIRP alpha and SHP-1 gene expression and erythrophagocytosis in vitro. SIRP alpha and SHP-1 expression was higher in monocytes from AIHA patients compared with normal, returning to normal after glucocorticoid therapy. SIRP alpha and SHP-1 mRNA expression was upregulated in healthy monocytes treated with dexamethasone compared with basal; however, the erythrophagocytic ability was not altered. Our results point to a minor role of SIRP alpha and SHP-1 in determining AIHA.

Metallopeptidase inhibitors arrest vital biological processes in the fungal pathogen Scedosporium apiospermum

P>Scedosporium apiospermum is an emerging agent of opportunistic mycoses in humans. Previously, we showed that mycelia of S. apiospermum secreted metallopeptidases which were directly linked to the destruction of key host proteins. In this study, we analysed the effect of metallopeptidase inhibitors on S. apiospermum development. As germination of inhaled conidia is a crucial event in the infectious process of S. apiospermum, we studied the morphological transformation induced by the incubation of conidia in Sabouraud-dextrose medium at 37 degrees C. After 6 h, some conidia presented a small projection resembling a germ-tube. A significant increase, around sixfold, in the germ-tube length was found after 12 h, and hyphae were exclusively observed after 24 h. Three distinct metallopeptidase inhibitors were able to arrest the transformation of conidia into hyphae in different ways; for instance, 1,10-phenanthroline (PHEN) completely blocked this process at 10 mu mol l-1, while ethylenediamine tetraacetic acid (EDTA) and ethylene glycol-bis (beta-aminoethyl ether; EGTA) only partially inhibited the differentiation at up to 10 mmol l-1. EGTA did not promote any significant reduction in the conidial growth, while PHEN and EDTA, both at 10 mmol l-1, inhibited the proliferation around 100% and 65%, respectively. The secretion of polypeptides into the extracellular environment and the metallopeptidase activity secreted by mycelia were completely inhibited by PHEN. These findings suggest that metallo-type enzymes could be potential targets for future therapeutic interventions against S. apiospermum.

Fungos anemófilos em Porto Alegre, RS.

O conhecimento dos fungos anemófilos em determinada cidade ou região é importante para o diagnóstico etiológico e o tratamento específico das manifestações alérgicas respiratórias. Várias técnicas quantitativas e qualitativas são preconizadas para coleta e identificação desses fungos na dependência do local estudado. Nesta pesquisa, sobre esporos de fungos do ar, foi utilizado o equipamento Rotorod Sampler®, que retira a amostra do ar através de um bastão de plástico preso a um motor elétrico que o faz girar rapidamente, sendo as partículas suspensas no ar recolhidas pelo bastão. As amostras foram coletadas uma vez por semana, durante 24 horas, correspondendo a um ciclo de coleta. Foram realizadas 52 coletas entre abril de 2000 e março de 2001. Os resultados mostraram prevalência de ascosporos (50,49%), Cladosporium (17,86%), Aspergillus/Penicillium (15,03%), basidiosporos (3,84%), rusts (3,82%), Helminthosporium (2,49%), Botrytis (1,22%), Alternaria (1,19%), smuts (0,90%), Curvularia (0,87%), Nigrospora (0,61%) e Fusarium (0,08%). Não foi possível identificar 1,59% dos esporos de fungos coletados no período. O maior número de esporos foi observado nos meses de verão e o menor, durante o outono. Utilizando provas in vivo e in vitro, avaliou-se a hipersensibilidade a fungos entre 39 pacientes atópicos sofrendo de rinite e ou asma brônquica. Os testes cutâneos identificaram sensibilização em 17,94% dos pacientes, enquanto as provas sorológicas caracterizaram presença de IgE específica em 12,82% dos casos avaliados. A detecção de significativo número de esporos de fungos no ar de Porto Alegre, com muitas espécies comprovadamente alergênicas, e os índices de sensibilização observados em indivíduos atópicos confirmam a importância do estudo dos fungos anemófilos nessa cidade, com vistas a aprimorar o diagnóstico e o manejo de pacientes com manifestações alérgicas respiratórias.