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.
Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with ultrastructural data, in order to better understand the molecular ways associated with iron- and copper-related pathology at subcellular level.
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.
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