RESUMEN
BACKGROUND: DNA methylation and histone modifications are the most identified modifications that selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis. AIM: We hypothesized that alterations in gene expression due to hypoxic-ischemic brain damage was regulated by epigenetic mechanisms including DNA methylation and histone methylation. STUDY DESIGN: To test this hypothesis, we established a rat model of HIE. Three groups were defined as hypoxic-ischemic, sham-operated, and control group. OUTCOME MEASUREMENTS: The validity of the HIE model used in this study was confirmed by histological and immunohistochemical tests. Gene expressions related with apoptosis and angiogenesis were studied at 0.5, 3, 6 and 24h after HI or sham operation. DNA and histone methylation status was studied in the genes showing significant change in expression. RESULTS AND CONCLUSIONS: Most of the genes related with apoptosis and angiogenesis (Epo, Epor, Hif 1α, Hif3α, VEGFa, VEGFc, Casp1, Casp9, and Casp8ap2) induced early after HI (30min). All of these genes were unmethylated at the beginning of the insult and in the control group. DNA methylation percentage and histone methylation (H3K36) levels were not correlated with gen expression levels. To our knowledge this is the first study evaluating the role of epigenetic mechanisms in HIE model, therefore the absence of similar studies don't allow us to compare the present results. Further studies investigating different epigenetic mechanisms are needed.
Asunto(s)
Metilación de ADN , Modelos Animales de Enfermedad , Epigénesis Genética/fisiología , Regulación de la Expresión Génica/fisiología , Hipoxia-Isquemia Encefálica/fisiopatología , Animales , Apoptosis/genética , Inmunoprecipitación de Cromatina , Histonas/metabolismo , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Neovascularización Fisiológica/genética , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
PURPOSE: The aim of this randomized controlled trial was to assess whether the addition of volume guarantee (VG) to triggered ventilation decreases the duration of ventilation in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). METHODS: Infants were randomized into two groups to initially receive either assist/control (A/C) or A/C plus VG ventilation and then weaned with synchronized intermittent mandatory ventilation (SIMV) or SIMV plus VG. RESULTS: Forty-five infants were included in the study. The demographic and clinical characteristics, values of tidal volume (VT), peak inspiratory pressure (PIP), fraction of inspired oxygen, carbon dioxide tension, and pH were similar for all participating infants initially. During the follow-up, the VT levels were more stable, and the PIP levels were significantly decreasing in the VG group. Although the duration of ventilation was shorter in the VG group, this trend was not statistically significant. The incidences of death and bronchopulmonary dysplasia (BPD) were not significantly different, but the combined outcome of death or BPD was lower in the VG group. Although the VG group experienced less frequent BPD, periventricular leukomalacia, and intraventricular hemorrhage, these differences were not statistically different. CONCLUSION: The VG option, when combined with A/C (in the acute phase of RDS) and SIMV (in the weaning), reduced VT variability, and may have shortened the duration of ventilation in VLBW infants. Overall mortality and BPD rates did not change, but their combined outcome was significantly improved in infants treated with VG modes as compared to those treated with synchronized pressure-limited modes alone.
