Urinary (1)H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment.

BACKGROUND: Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months. OBJECTIVES: As in this short-term trial, as in others, it is impracticable to monitor response to therapy or treatment by liver biopsy, we aimed to identify a panel of potential non-invasive metabolic biomarkers by a urinary metabolic profiling. METHODS: Urine samples from a group of 31 pediatric NAFLD patients, enrolled in a VSL#3 clinical trial, were analyzed by high-resolution proton nuclear magnetic resonance spectroscopy in combination with analysis of variance-Simultaneous Component Analysis model and multivariate data analyses. Urinary metabolic profiles were interpreted in terms of clinical patient feature, treatment and chronology pattern correlations. RESULTS: VSL#3 treatment induced changes in NAFLD urinary metabolic phenotype mainly at level of host amino-acid metabolism (that is, valine, tyrosine, 3-amino-isobutyrate or ß-aminoisobutyric acid (BAIBA)), nucleic acid degradation (pseudouridine), creatinine metabolism (methylguanidine) and secondarily at the level of gut microbial amino-acid metabolism (that is, 2-hydroxyisobutyrate from valine degradation). Furthermore, some of these metabolites correlated with clinical primary and secondary trial end points after VSL#3 treatment: tyrosine and the organic acid U4 positively with alanine aminotransferase (R=0.399, P=0.026) and BMI (R=0.36, P=0.045); BAIBA and tyrosine negatively with active glucagon-like-peptide 1 (R=-0.51, P=0.003; R=-0.41, P=0.021, respectively). CONCLUSIONS: VSL#3 treatment-dependent urinary metabotypes of NAFLD children may be considered as non-invasive effective biomarkers to evaluate the response to treatment.

[Normal urinary levels of telopeptide aminoterminal (NTx) of type I collagen in healthy term newborns and infants in the first month of life]. / Livelli normali urinari di telopeptide amino terminale (NTx) del collagene di tipo I in neonati a termine e lattanti sani nei primi tre mesi di vita.

The Authors have studied urinary aminoterminal telopeptide of type I collagen (NTx), a bone catabolism marker of recent determination, by an enzyme-linked immunoassorbent assay (OSTEOMARK) in 80 urine samples of term healthy infants in the first 3 months of life. Highly significant variations have been compared in the whole period studied (P = 0.000). Levels of NTx increase significantly from 1 to 7 days of life, reaching a plateau that is kept until 45th day and then significantly decrease until 90th day, when, however, they result higher than the values reported in literature concerning older ages. The Authors conclude that even this bone catabolism marker is influenced, in the first week of life, by the particular phenomenology linked to the neonatal adaptation, and that, subsequently, shows a trend strictly linked to the bone turnover modifications throughout the faster stage of the growth.

[Normal levels of collagen-type-I telopeptide in the first 90 days of life]. / Livelli normali di telopeptide del collagene di tipo I nei primi 90 giorni di vita.

Serum levels of carboxyterminal telopeptide of type I collagen (ICTP), a marker of matrix degradation, were measured by RIA test, on 184 samples of healthy newborns and children aging from 1 (cord blood) to 90 days of life. We found ICTP values about tenfold higher than the adults', with highly significant variations (P < 0.001) in the whole period studied. During the first three months of life serum levels of the bone marker show a progressive increase from 0 to 7 days, they remain unchanged until the 30th day and then decrease until the 45th day, maintaining similar values from the 45th to the 90th day of life. The authors think that the pattern of ICTP in the first week of life is under the influence of the adapting phenomena following delivery, in which catabolic processes are predominant, while in the second period ICTP modifications are related to growing processes and then to bone turnover.

Rubinstein-Taybi syndrome associated with Dandy-Walker cyst. Case report in a newborn.

Rubinstein-Taybi is a rare malformative syndrome characterized by dysmorphic features and mental retardation. Early diagnosis in neonatal age can be facilitated by the presence of characteristic broadening of the distal phalanges of thumbs and great toes. Most of the cases are sporadic. Associated malformations such as bone anomalies, heart malformations, cell immunity deficits and metabolic alterations have been observed. This paper reports the first case of Rubinstein-Taybi syndrome associated with Dandy-Walker type cerebral malformation diagnosed in the neonatal period.