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Congenital Sodium Diarrhea (CSD) due to SLC9A3 mutation is a rare cause of neonatal diarrhea explained by dysfunction of the Na+/H+ antiporter 3 in intestine. To date only 10 patients have been described. We report a male patient with typical antenatal symptoms (polyhydramnios and intestinal dilation) and neonatal diarrhea with fecal sodium and bicarbonates loss. Next generation sequencing revealed a missense homozygous mutation in exon 6 of the SLC9A3 gene (NM_004174.3:c.1039G > A, NP_004165.2:p.Glu347Lys). Oral electrolytes supplements (Sodium and Bicarbonates) allowed a normal growth to the child currently aged twenty months. CSD symptomatology usually begins during third trimester of pregnancy. Antenatal signs are polyhydramnios and diffuse intestinal dilation. Main differential diagnoses are intestinal obstruction and Congenital Chloride Diarrhea. Diarrhea begins from the first days of life and its severity is variable. Based on the report and on the literature we suggest that non syndromic CSD can be detected during third trimester of pregnancy. With adequate electrolytes supplementation good evolution is possible., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background & Aims: The main hindrance in promoting living donor liver transplantation remains the morbi-mortality risk for the donor. Considering the opposed remodeling influence of portal and hepatic artery flows, our working hypothesis was to identify a lobar portal vein stenosis capable of inducing a contralateral liver mass compensatory enlargement, without the downstream ipsilateral atrophic response., Methods: Twenty-four pigs entered this study. Six of them were used to establish hemodynamic changes following a progressive left portal vein (LPV) stenosis, in blood flow, pressure and vessel diameter of the LPV, main portal vein and hepatic artery. Sixteen pigs were divided into 4 groups: sham operated animals, 20% LPV stenosis, 50% LPV stenosis, and 100% LPV stenosis. Daily liver biopsies were collected until post-operative day 5 to investigate liver regeneration and atrophy (Ki67, STAT3, LC3, and activated caspase 3) according to the degree of LPV stenosis. Finally, changes in liver volumetry after 20% LPVS were investigated., Results: A 20% LPV stenosis led to dilatation of the hepatic artery and a subsequent four-fold increase in hepatic arterial flow. Concomitantly, liver regeneration was triggered in the non-ligated lobe and the cell proliferation peak, 5 days after surgery, was comparable to that obtained after total LPV ligation. Moreover, 20% LPV stenosis preconditioning did not induce left liver atrophy contrary to 50 and 100% LPV stenosis., Conclusions: A 20% LPV stenosis seems to be the adequate preconditioning to get the remnant liver of living donor ready to take on graft harvesting without atrophy of the future graft., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Preeclampsia is a pregnancy disorder being a leading cause of maternal and fetal mortality and morbidity. It is a complex multisystem disease characterized by hypertension and proteinuria. In preeclampsia the placenta releases factors into the maternal circulation which cause a systemic endothelial dysfunction. Here, we review data demonstrating the central role played by the endothelium in the development of the maternal syndrome of preeclampsia. We present also original data showing how circulating factors present in the plasma of preeclamptic women can alter the transcriptome of endothelial cells. The expression of genes involved in essential functions such as vasoregulation, oxidative stress, apoptosis and cell proliferation show differential expression when endothelial cells are exposed to preeclamptic or normal pregnancy plasma. We conclude by discussing the growing evidences that the alterations of the endothelium during preeclampsia are linked to an increased risk of cardiovascular diseases latter on life. Therefore, a better understanding of the modifications undergone by the endothelial cells during preeclampsia is essential to develop new therapeutic approaches to both, manage preeclampsia and to prevent the long-term sequelae of the disease on women cardiovascular system., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology., Methods: This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification., Results: Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology., Conclusions: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Intra-uterine growth restriction (IUGR) is defined by a restriction of fetal growth during gestation. It is a prevalent significant public health problem that jeopardizes neonatal health but also that can have deleterious consequences later in adult life. Cullins constitute a family of seven proteins involved in cell scaffold and in selective proteolysis via the ubiquitin-proteasome system. Most Cullins are critical for early embryonic development and mutations in some Cullin genes have been identified in human syndromes including growth retardation. Our work hypothesis is that Cullins, particularly CUL4B and CUL7, are involved in placental diseases and especially in IUGR. Thus, expression of Cullins and their cofactors was analyzed in normal and pathological placentas. We show that they present a constant significant over-expression in IUGR placentas, whose extent is dependent on the position of the interrogated fragment along the cDNAs, suggesting the existence of different isoforms of the genes. Particularly, the CUL7 gene is up-regulated up to 10 times in IUGR and 15 times in preeclampsia associated with IUGR. The expression of cofactors of Cullins participating to functional complexes has also been evaluated and showed a similar significant increase in IUGR. Promoters of Cullin genes appeared to be under the control of the SP1 transcription factor. Finally, methylation levels of the CUL7 promoter in placental tissues are modulated according to the pathological conditions, with a significant hypomethylation in IUGR. These results concur to pinpoint the Cullin family as a new set of markers of IUGR., (2009 Elsevier Ltd. All rights reserved.)