Development of the Gastrointestinal Tract in Newborns as a Challenge for an Appropriate Nutrition: A Narrative Review

The second and third trimesters of pregnancy are crucial for the anatomical and functional development of the gastrointestinal (GI) tract. If premature birth occurs, the immaturity of the digestive and absorptive processes and of GI motility represent a critical challenge to meet adequate nutritional needs, leading to poor extrauterine growth and to other critical complications. Knowledge of the main developmental stages of the processes involved in the digestion and absorption of proteins, carbohydrates, and lipids, as well as of the maturational phases underlying the development of GI motility, may aid clinicians to optimize the nutritional management of preterm infants. The immaturity of these GI systems and functions may negatively influence the patterns of gut colonization, predisposing to an abnormal microbiome. This, in turn, further contributes to alter the functional, immune, and neural development of the GI tract and, especially in preterm infants, has been associated with an increased risk of severe GI complications, such as necrotizing enterocolitis. Deeper understanding of the physiological colonization patterns in term and preterm infants may support the promotion of these patterns and the avoidance of microbial perturbations associated with the development of several diseases throughout life. This review aims to provide a global overview on the maturational features of the main GI functions and on their implications following preterm birth. We will particularly focus on the developmental differences in intestinal digestion and absorption functionality, motility, gut–brain axis interaction, and microbiomes

AMP-activated protein kinase - not just an energy sensor

Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy. In this article, we discuss a few interesting recent developments in the AMPK field. Firstly, we review recent findings on the canonical pathway by which AMPK is regulated by adenine nucleotides. Secondly, AMPK is now known to be activated in mammalian cells by glucose starvation by a mechanism that occurs in the absence of changes in adenine nucleotides, involving the formation of complexes with Axin and LKB1 on the surface of the lysosome. Thirdly, in addition to containing the nucleotide-binding sites on the γ subunits, AMPK heterotrimers contain a site for binding of allosteric activators termed the allosteric drug and metabolite (ADaM) site. A large number of synthetic activators, some of which show promise as hypoglycaemic agents in pre-clinical studies, have now been shown to bind there. Fourthly, some kinase inhibitors paradoxically activate AMPK, including one (SU6656) that binds in the catalytic site. Finally, although downstream targets originally identified for AMPK were mainly concerned with metabolism, recently identified targets have roles in such diverse areas as mitochondrial fission, integrity of epithelial cell layers, and angiogenesis

Micro Opioid Receptor A118G Polymorphism and Post-Operative Pain: Opioids' Effects on Heterozigous Patients

The Single-Nucleotide-Polymorphism (SNP) 118A&gt;G in the μ-1 Opioid Receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether 118A&gt;G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section α, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section β, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section β we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by Cortisol levels. In section α, with cluster analysis, subjects were analyzed according to their genotype: a group (#1) of 34 patients reporting VAS score &gt;3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A&gt;G polymorphism) patients were unevenly distributed between those with cluster #2 (VAS score &lt;3 at every study steps) and those with cluster #3 (VAS score progressively reducing from T6h). In section (3, A118G carriers receiving epidural sufentanil had the lowest VAS scores at T24h; also in these patients, Cortisol levels remained more stable, with a mild decrease at T6h. This study shows that the OPRM1 118A&gt;G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy. </jats:p

Micro opioid receptor A118G polymorphism and post-operative pain: opioids' effects on heterozygous patients.

The single-nucleotide-polymorphism (SNP) 118A>G in the micro-1 opioid receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether 118A >G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section alpha, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section beta, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section beta we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by cortisol levels. In section alpha, with cluster analysis, subjects were analyzed according to their genotype: a group (no. 1) of 34 patients reporting VAS score >3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A>G polymorphism) patients were unevenly distributed between those with cluster no. 2 (VAS score G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy