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Asma infantil.

ABSTRACT: El asma es la enfermedad crónica infantil más frecuente. El diagnóstico es fácil en la mayoría de las ocasiones por la aparición de episodios de disnea espiratoria con sibilancias reversibles espontáneamente o por el efecto de broncodilatadores. En el momento del diagnóstico, se requieren tres pruebas complementarias: las radiografías de tórax, las pruebas funcionales respiratorias y un estudio alergológico. El tratamiento de las exacerbaciones se basa en los beta2-adrenérgicos inhalados y, si es preciso, en la corticoterapia oral. El objetivo del tratamiento de fondo es mantener el control, prevenir las exacerbaciones y restaurar o mantener las funciones pulmonares normales. Se debe adaptar al nivel de control del asma y en él tiene un lugar destacado la corticoterapia inhalada y los broncodilatadores de acción prolongada. En los menores de tres años, el asma se diagnostica a partir de tres episodios de sibilancias. Se debe buscar la presencia de antecedentes particulares, de manifestaciones atípicas o persistentes y de anomalías en la radiografía de tórax para descartar las demás causas de manifestaciones sibilantes recidivantes. Cuando es necesario un tratamiento de fondo, se basa en la corticoterapia inhalada. Las cohortes prospectivas han permitido demostrar que la atopia, la gravedad clínica y la persistencia de una obstrucción clínica son los factores principales tanto de la persistencia como de la gravedad del asma durante la vida.

SUBMITTER: de Blic J

PROVIDER: S-EPMC7147675 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Project description:The outer membrane (OM) is an essential structure of Gram-negative bacteria that provides mechanical strength and protection from large and/or hydrophobic toxic molecules, including many antibiotics. The OM is composed of glycerophospholipids (GPLs) and lipopolysaccharide (LPS) in the inner and outer leaflets, respectively, and hosts integral β-barrel proteins and lipoproteins. While the systems responsible for translocation and insertion of LPS and OM proteins have been elucidated, the mechanism(s) mediating transport of GPLs from the inner membrane to the OM has remained elusive for decades. Very recently, studies performed in Escherichia coli proposed a role in this process for AsmA-like proteins that are predicted to share structural features with eukaryotic lipid transporters. In this study, we provide the first systematic investigation of AsmA-like proteins in a bacterium other than E. coli, the opportunistic human pathogen Pseudomonas aeruginosa. Bioinformatic analyses revealed that P. aeruginosa possesses seven AsmA-like proteins. Deletion of asmA-like genes in many different combinations, coupled with conditional mutagenesis, revealed that four AsmA-like proteins are redundantly essential for growth and OM integrity in P. aeruginosa, including a novel AsmA-like protein (PA4735) that is not present in E. coli. Cells depleted of AsmA-like proteins showed severe defects in the OM permeability barrier that were partially rescued by lowering the synthesis or transport of LPS. Since fine balancing of GPL and LPS levels is crucial for OM integrity, this evidence supports the role of AsmA-like proteins in GPL transport toward the OM.ImportanceGiven the importance of the outer membrane (OM) for viability and antibiotic resistance in Gram-negative bacteria, in the last decades, several studies have focused on the characterization of the systems involved in OM biogenesis, which have also been explored as targets for antibacterial drug development. However, the mechanism mediating translocation of glycerophospholipids (GPLs) to the OM remained unknown until recent studies provided evidence that AsmA-like proteins could be responsible for this process. Here, we demonstrate for the first time that AsmA-like proteins are essential and redundant for growth and OM integrity in a Gram-negative bacterium other than the model organism Escherichia coli and demonstrate that the human pathogen Pseudomonas aeruginosa has an additional essential AsmA-like protein that is not present in E. coli, thus expanding the range of AsmA-like proteins that play key functions in Gram-negative bacteria.

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Asma infantil.

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