Paola Pirillo

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns

Background:Acylcarnitines are biomarkers of fatty acid metabolism, and examining their patterns in preterm newborn may reveal metabolic changes associated with particular conditions related to prematurity. Isomeric acylcarnitines in dried blood spots (DBS) and plasma have never been assessed in preterm infants.Methods:We studied 157 newborn divided into four groups by weeks of gestational age (GA), as follows: 22–27 wk in group 1; 28–31 wk in group 2; 32–36 wk in group 3; and 37–42 wk in group 4. Samples were collected on the third day of life. Acylcarnitines were separated and quantified using ultra-performance liquid chromatography tandem mass spectrometry.Results:Acylcarnitine concentrations correlated significantly with GA and birth weight in both DBS and plasma samples. Concentrations were lower in preterm newborn, except for acylcarnitines derived from branched-chain amino acids, which were higher and correlated with enteral feeding. On day 3 of life, no correlations emerged with gender, respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, or mechanical ventilation.Conclusion:We established GA-based reference ranges for isomeric acylcarnitine concentrations in preterm newborn, which could be used to assess nutritional status and the putative neuroprotective role of acylcarnitines.

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes

Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference.

Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI–MS/MS urinary profiling of inborn errors of bile acid synthesis

Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3-TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids.

Wheezing preschool children with early-onset asthma reveal a specific metabolomic profile

Many children of preschool age present with recurrent wheezing. Most of them outgrow their symptoms, while some have early‐onset asthma. Aim of this prospective preliminary study was to apply a metabolomic approach to see whether biochemical‐metabolic urinary profiles can have a role in the early identification of the children with asthma.

Asymmetric dimethylarginine and related metabolites in exhaled breath condensate of children with cystic fibrosis

Asymmetric dimethylarginine (ADMA) competitively inhibits nitric oxide synthase (NOS). Its levels in specimens from murine models and asthmatic patients are related to inflammation and oxidative stress. Patients with cystic fibrosis(CF) reportedly have higher arginase activity, lower NO production and NOS expression than healthy controls.

Metabolomic Profile of Amniotic Fluid and Wheezing in the First Year of Life—A Healthy Birth Cohort Study

Objectives To apply metabolomic analysis of amniotic fluid in a discovery cohort to see whether a specific biochemical‐metabolic profile at birth is associated with the subsequent onset of wheezing over the first year of life. Study design This prospective exploratory study was conducted in a healthy term‐born Dutch cohort recruited at 2 hospitals in Utrecht (UMCU, Utrecht, and Diakonessenhuis, Utrecht), The Netherlands. A metabolomic approach based on mass spectrometry was applied to analyze 142 amniotic fluid samples collected at birth. The infants were followed up during their first year of life with recording any respiratory symptoms daily, and they were classified according to the onset of wheezing. Results Orthogonally constrained projection to latent structures discriminant analysis was used to investigate differences in the metabolic profiles of the infants with (n = 86) and without (n = 56) wheezing. A search of the available databases for amniotic fluid metabolites identified by stability selection, combined with pathway analysis, highlighted the possible metabolic perturbations involved in this condition. The model built using 16 relevant variables with plausible biological significance, showed an area under the curve of 0.82 (P < .001) and an area under the curve calculated by 7‐fold full cross‐validation of 0.72 (P = .003), with the steroid hormone biosynthesis and the 2‐phenylalanine metabolism emerging as probably perturbed pathways. Conclusions Infants who will or will not experience wheezing in their first year of life have distinct amniotic fluid metabolomic profiles at birth. Changes occurring in biochemical‐metabolic pathways in late intrauterine life may have a pathogenic role in early‐onset wheezing.