Background
Use of in silico bioinformatics analyses has led to important leads in the complex nature of alcoholism at the genomic, epigenomic, and proteomic level, but has not previously been successfully translated to the development of effective pharmacotherapies. In this study, a bioinformatics approach led to the discovery of neuroimmune pathways as an age-specific druggable target. Minocycline, a neuroimmune modulator, reduced high ethanol drinking in adult, but not adolescent, mice as predicted a priori.
Methods
Age and sex-divergent effects in alcohol consumption were quantified in FVB/NJ × C57BL/6J F1 mice given access to 20% alcohol using a 4 hr/day, 4-day Drinking-In-Dark (DID) paradigm. In silico bioinformatics pathway over-representation analysis for age-specific effects of alcohol in brain was performed using gene expression data collected in control and DID-treated, adolescent and adult, male mice. Minocycline (50 mg/kg i.p., once daily) or saline alone was tested for an effect on ethanol intake in the F1 and C57BL/6J (B6) mice across both age and gender groups. Effects of minocycline on the pharmacokinetic properties of alcohol were evaluated by comparing the rates of ethanol elimination between the saline and minocycline treated F1 and B6 mice.
Results
Age and gender differences in DID consumption were identified. Only males showed a clear developmental increase difference in drinking over time. In silico analyses revealed neuroimmune-related pathways as significantly over-represented in adult, but not adolescent, male mice. As predicted, minocycline treatment reduced drinking in adult, but not adolescent, mice. The age effect was present for both genders, and in both the F1 and B6 mice. Minocycline had no effect on the pharmacokinetic elimination of ethanol.
Conclusions
Our results are a proof of concept that bioinformatics analysis of brain gene expression can lead to the generation of new hypotheses and a positive translational outcome for individualized pharmacotherapeutic treatment of high alcohol consumption.
Histoplasmosis is an important mycosis in the Americas; and in children with no immune system abnormalities, histoplasmosis is typically a self-limited process. In contrast, in children with immune problems, disease manifestations are frequently more severe and include dissemination. From 1984 to 2010, a retrospective study of paediatric patients who had been diagnosed with histoplasmosis was performed. A total of 45 pediatric cases of histoplasmosis were identified. The most important risk factor was malnutrition (37%), followed by environmental exposure (33%). The patients exhibited pulmonary infiltrates (83%), fever (76%), cough, constitutional symptoms (38%), headache (35%), and lymph node hypertrophy (33%). Concerning the clinical forms, 64% of the patients presented with the progressive disseminated form that frequently affected the central nervous system (48%). Diagnostic laboratory tests indicated that the cultures were positive for 80% of the patients, the agar gel immunodiffusion was reactive in 95%, the M band of the precipitate was more commonly observed (81%), and the complement fixation tests were reactive in 88% of the patients. The timely diagnosis of histoplasmosis is important, and for this reason, it is hoped that the results of this study will lead pediatricians toward a better understanding of this mycosis in children.
El presente trabajo tiene por objeto conocer la dinámica del mercado mundial de aguacate enun escenario proyectado de tiempo. Para ello, se realizó una búsqueda sistemática deinformación, relacionada con los datos de producción, importaciones y exportaciones deaguacate, mediante la recopilación de bases de datos especializadas, realizando cálculos yproyecciones para conocer el comportamiento del mercado del aguacate. Se concluye que elaguacate es un frutal promisorio, con margen de crecimiento en los mercados internacionalestanto en precio como en cantidad; encontrándose, además, que el consumo per cápita aparentede este frutal tenderá a situarse en 0,85 kilogramos de consumo por persona año, en el 2020; loanterior, favorece los intereses de los países productores que ven es esta fruta una oportuni-dad para generar ingresos en todos los niveles de la cadena de valor.
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