Nutrition, growth and body composition in preterm infants

The goal of neonatal nutrition in the preterm infant is to achieve postnatal growth and body composition approximating that of a normal fetus of the same postmenstrual age and to obtain a functional outcome comparable to infants born at term. However, in clinical practice such a pattern is seldom achieved, with growth failure and altered body composition being extensively reported. The BabyGrow preterm nutrition study was a longitudinal, prospective, observational study designed to investigate nutrition and growth in 59 preterm infants following the implementation of evidence-based nutrition guidelines in the neonatal unit at Cork University Maternity Hospital. Nutrient delivery was precisely measured during the entire hospital stay and intakes were compared with current international recommendations. Barriers to nutrient delivery were identified across the phases of nutritional support i.e. exclusive parenteral nutrition and transition (establishment of enteral feeds) phases of nutrition and nutritional strategies to optimise nutrient delivery were proposed according to these phases. Growth was measured from birth up to 2 months corrected age and body composition was assessed in terms of fat mass and lean body mass by air displacement plethysmography (PEA POD) at 34 weeks gestation, term corrected age and 2 months corrected age. Anthropometric and body composition data in the preterm cohort were compared with a term reference group from the Cork BASELINE Birth Cohort Study (n=1070) at similar time intervals. The clinical and nutritional determinants of growth and body composition during the neonatal period were reported for the first time. These data have international relevance, informing authoritative agencies developing evidence-based practice guidelines for neonatal nutritional support. In the future, the nutritional management of preterm infants may need to be individualised to consider gestational age, birth weight as well as preterm morbidity.

A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD.