Overlapping between CYP3A4 and CYP3A7 expression in the fetal human liver during development.

OBJECTIVE: The cytochrome P450 (CYP450) superfamily is implicated in important life processes, including metabolism of many molecules. CYP3A account for the largest portion of CYP450 proteins in human, including CYP3A4, CYP3A5 and CYP3A7. The purpose of this study was to investigate the immunohistochemical expression of CYP3A4 and CYP3A7 in human liver at different post-conceptional (PC) ages. METHODS: Human liver samples from 30 fetuses and newborns were, clustered according with the PC age, routinely processed for immunohistochemical analysis of CYP3A4 and CYP3A7. RESULTS: CYP3A4 was positive in all but two cases, CYP3A7 was positive in all but one case, which was negative also for CYP3A4. CONCLUSIONS: Our data on immunohistochemical detection of CYP3A4 and CYP3A7 during development show that CYP3A4 expression is not restricted to the post-natal age, being the immunostaining for both CYP3A4 and CYP3A7 identical after 25 weeks of PC age, thus the relationship between these CYP450 isoforms should be considered much more complex than previous thought. A high interindividual variability was observed among subjects at all gestational age. The variable CYP3A expression suggests the existence of a marked interindividual variability in drug metabolism during the intrauterine life and in perinatal period.

The role of novel biomarkers in early diagnosis and prognosis of acute kidney injury in newborns.

Acute kidney injury (AKI) refers to the rapid loss of renal function. In clinical practice, AKI is common among hospitalized patients of all age groups including neonates and remains an important cause of morbidity and mortality due to its late diagnosis and therefore delayed therapeutic intervention. Although the precise incidence of AKI in newborn is unknown, several studies have reported that 8 to 24% of all critically ill newborns in neonatal intensive care units may develop the condition. We aim at reviewing the existing literature on novel serum and urinary biomarkers and discuss their role in the early diagnosis and prognosis of AKI in newborns. Specifically, this review will focus on cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in serum and on CysC, NGAL, kidney injury molecule-1, and IL-18 in urine.

An experimental model of neonatal normocapnic hypoxia and resuscitation in Landrace/Large White piglets.

OBJECTIVE: The aim of this study is to describe and evaluate an experimental model of neonatal normocapnic hypoxia and resuscitation. METHODS: Ten male Landrace/Large White neonatal piglets were studied. Following anaesthesia and intubation, the animals were mechanically ventilated. Surgical procedures included catheterization of the right internal jugular vein and the carotid artery. After stabilization with 21% O(2), normocapnic hypoxia was induced by decreasing the inspired O(2) to 6-8%. When piglets developed bradycardia (heart rate < 60 beats/min), reoxygenation was initiated by administering 21% O(2). Arterial blood samples were taken during baseline, hypoxia and reoxygenation in order to measure interleukine-6 and interleukine-8. RESULTS: Nine out of ten animals were successfully resuscitated (one of these required chest compressions and a dose of adrenaline) and one died despite resuscitation efforts. After returning to baseline haemodynamic values, euthanasia was performed using thiopental overdose. CONCLUSIONS: Haemodynamic fluctuations at baseline, during normocapnic hypoxia and reoxygenation in Landrace/Large White piglets are comparable to that in human neonates, making the breed a favorable model of human neonatal hypoxia investigation.

Thymosin beta 10 expression in developing human salivary glands.

Thymosin beta 10 (Tß10) is a member of beta-thymosins (Tßs), a family of low molecular mass peptides abundant in many cell types. In previous studies, Tßs have been shown to play essential roles in many cellular functions, including cytokinesis, migration and endocytosis. Recently, Tß10 has been found in high quantities in the saliva of human newborns, while it disappeared in the adults. On the basis of these data, it seemed of some interest to study the influence of Tß10 during the development of the human salivary glands. To this end, we analyzed, using immunocytochemistry, the expression of Tß10 in samples of the major and minor salivary glands obtained, at autopsy, from 2 human fetuses and 4 newborns, ranging from 13 up to 33weeks of gestation. Tß10 immunoreactivity was detected in all salivary glands examined, with marked differences from one gland to the next, the parotid glands showing the highest Tß10 reactivity and minor salivary glands the lowest reactivity. Marked changes were observed in Tß10 expression and localization during embryogenesis. Tß10 was mainly localized extracellularly in the youngest human fetuses (13weeks), in the cytoplasm of immature duct cells at 20weeks, in acinar cells and in the duct lumen in 33weeks old fetuses. Our data show, for the first time, a strong expression of Tß10 in the human salivary glands during the initial phases of the physiological development, present at the 13th week of gestation, and suggesting a role for the peptide in the salivary glands' organogenesis.