High Prevalence of Esophageal Acid Exposure in Very Low Birth Weight Infants Presenting or Not Bronchopulmonary Dysplasia: A Prospective Cross-Sectional Study

Abstract

IntroductionBronchopulmonary dysplasia (BPD) affects about 22% of very low birth weight (VLBW) newborns [1]. The disease has a turbulent clinical course, significantly contributing to morbidity and mortality in the neonatal period, and leaving long-term sequelae [2].The frequency of Gastroesophageal Reflux (GER) causing symptoms and a complicated clinical course in premature infants presenting BPD during their stay in neonatal care units is not fully established [3][4][5] and widely questioned.Although there is experimental and clinical evidence that sleep apnea occurs as a result of reflux episodes [6,7], the cause-effect relation between the conditions is controversial [8][9][10]. Similarly there is disagreement regarding the effects of GER in the pathogenesis and in BPD recovery [5,11]. The presence of pepsin in the tracheal aspirate in ventilated newborns during the first weeks of life, and the subsequent progression to BPD in these newborns may indicate the possibility of chronic aspiration as a mechanism in the genesis of BPD [12]. Furthermore, there is evidence that symptoms associated with acid reflux episodes that reach or not the pharynx, if cleared slowly, are common in newborns presenting BPD on respiratory support [13,14].Despite the controversies, the presumptive diagnosis of GER has been quite frequent in neonatal units in North America, and there is indication that 24.8% of VLBW infants are treated for the condition [15]. Treatment is even more common (47.6%) among VLBW infants who are discharged after 42 weeks of postmenstrual age, of which 75.7% have DBP [15].Given the uncertainty regarding the occurrence of GER in newborns presenting BPD and the frequency of GER treatment, the prospective study of distal esophagic pH monitoring (DEpHM) abnormalities in newborn infants presenting or not BPD was considered. AbstractBackground: A high frequency of treatment for gastroesophageal reflux disease is observed in neonates with Bronchopulmonary Dysplasia (BPD). The association between these illnesses is controversial.

Multi-Layered Epigenetic Regulatory Mechanisms Mediate Epithelial to Mesenchymal Transition in Cancer

“…It is thought that the absence of such signalling can cause MET; thus, continuous signalling is essential for maintaining the mesenchymal characteristics of cells undergoing EMT [12,13]. Numerous growth factors such as transforming growth factor-beta (TGF-β), fibroblast growth factor (FGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) can induce EMT by triggering a number of different signalling pathways including TGF-β, Wnt, and Notch [11,[14][15][16][17][18]. Combinatorial activation of these signalling pathways results in the activation of several EMT-inducing transcription factors (EMT-TFs) such as Snail, Slug, ZEB-1, ZEB-2, Twist, and members of the NF-κB family [15,16,[19][20][21][22][23][24][25].…”

“…Several epigenetic inhibitors have been shown to be effective repressors of EMT: predominantly by upregulating E-cadherin. Treatment with the DNMT inhibitor 5-aza-2′-deoxycytidine (5-Aza-dC) blocks CDH1 hypermethylation: restores E-cadherin expression: and initiates morphological MET in numerous cancer types [142,143]. 5-Aza-dC treatment also increases E-cadherin expression and in vivo metastases of breast cancer cells in a SCID mouse xenograft model [144].…”