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Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT) is one of the principal risk factors associated with death. Chronic kidney disease (CKD), which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or over feeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the 'early programming' of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a 'factor of vulnerability' when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT) is one of the principal risk factors associated with death. Chronic kidney disease (CKD), which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or over feeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the "early programming" of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a "factor of vulnerability" when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways. [ABSTRACT FROM AUTHOR]

Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 ( pancreatic and duodenal homeobo x protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors ( Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionnally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In recent years ibuprofen has been proposed for the treatment of patent ductus arteriosus (PDA) as it has been proved to be equally as effective as indomethacin and shows fewer cerebral blood flow, intestinal and renal hemodynamic effects. A number of studies and several meta-analyses comparing both drugs are now available that debate whether indomethacin or ibuprofen should be used for PDA prophylaxis or closure. This review examines the available knowledge on the specific issue of the effects of ibuprofen on kidney function, as improved renal tolerance is a major argument in favor of its use in the routine treatment of PDA. There is sufficient evidence to consider that ibuprofen, at the currently proposed dosing regimen, has a similar efficacy to indomethacin but is better tolerated by the neonatal kidney when employed for the treatment of established PDA. However, adverse effects of ibuprofen have been evidenced both in trials on the use of ibuprofen for the prevention of PDA and of intraventricular hemorrhage-periventricular hemorrhage (IVH PVH), and in experimental studies on a neonatal, anesthetized animal model. Thus ibuprofen, as with other cyclooxygenase (COX) inhibitors, may not be exempt from causing renal adverse effects, especially in circumstances when renal prostaglandin activation is maximal (i.e., when administrated early after birth, in more immature patients and in certain situations such as in the anesthetized rabbit). However, although the issue has been addressed extensively in the last decades, there is insufficient evidence that therapeutic intervention in PDA is beneficial in terms of mortality or clinically significant morbidity outcomes. Studies aimed at resolving this key issue are still needed. [ABSTRACT FROM AUTHOR]