Massimo Pettoello-Mantovani

Urea-induced ROS accelerate senescence in endothelial progenitor cells

BACKGROUND AND AIMSnThe pathogenic events responsible for the reduction of endothelial progenitor cell (EPC) number and function seen in patients with chronic renal failure (CRF) are poorly understood. Here we investigate the hypothesis that increased concentrations of urea associated with CRF increase ROS production directly in EPCs, causing abnormalities associated with coronary artery disease risk.nnnMETHODSnHuman EPCs were isolated from peripheral blood mononuclear cells of healthy donors and cultured in the presence or absence of 20xa0mmol/L urea.nnnRESULTSnUrea at concentrations seen in CRF induced ROS production in cultured EPCs. Urea-induced ROS reduced the number of endothelial cell colony forming units, uptake and binding of Dil-Ac-LDL and lectin-1, and the ability to differentiate into CD31- and vascular endothelial growth factor receptor 2-positive cells. Moreover, urea-induced ROS generation accelerated the onset of EPC senescence, leading to a senescence-associated secretory phenotype (SASP). Normalization of mitochondrial ROS production prevented each of these effects of urea.nnnCONCLUSIONSnThese data suggest that urea itself causes both reduced EPC number and increased EPC dysfunction, thereby contributing to the pathogenesis of cardiovascular disease in CRF patients.

Guidance on the use of probiotics in clinical practice in children with selected clinical conditions and in specific vulnerable groups

The use of probiotics has been covered by many guidelines, position papers and evidence‐based recommendations, but few have referred to specific patient groups or clinical indications. This review summarises recommendations and scientifically credited guidelines on the use of probiotics for children with selected clinical conditions and provides practice points.

Improving Community and Primary Care Services for Children, Adolescents, and Their Families in Europe

Many healthcare systems in Europe are undergoing significant reconfigurations toward a more populationoriented delivery model to tackle the “new morbidities.” These transformations should be backed by reforms, which emphasize the importance of community and primary care services for children, adolescents, and their families, and the key roles that legislators and governments contribute to Public Health. In fact, equitable financial investment in public health policies are a key factor to overcome the current concerns of rising healthcare costs, substantial gaps in quality, and increasing demand for services. This approach will require greater collaboration and coordination between traditional health service sectors, public health, and nonclinical services to accomplish cost containment, while simultaneously improving patient outcomes. New models and programs that link clinical, social, community, public health, and governmental programs are needed. We will describe the essential elements of a consensus statement that examines the community and primary care elements of the system.

Never-Ending Stories, the Loop in Pediatrics—How Many Pediatricians Need to be Trained in European Countries to Keep the Pediatric Workforce Stable?

I n today’s world, looping seems to be a universal constant in many contexts—whether in music, media, politics, or healthcare. In pediatrics, the self-contained loop is an essential part of the never-ending question “What is the scope of pediatrics?” It is highly questionable whether any positive advantage exists for society when pediatricians from different countries practice endless, unresolved discussions within relatively closed circles about questions such as “what is a pediatrician?” or “how many pediatricians are needed nationally to keep the pediatric workforce stable and effective?” This commentary aims to raise the attention of legislators and the pediatric community on the risk of a shortage of pediatricians and its negative social impact that the civil society will face shortly, particularly in the Western world. In Europe, not enough pediatric graduates are currently entering the profession to replace those who retire. The task force of the European Paediatric Association/Union of National European Paediatric Societies and Associations’ (EPA/UNEPSA) Scientific Advisory Board, which is studying this circumstance, has developed an equation for estimating the needed annual number of newly trained pediatricians. This equation could be adapted to different national European contexts, assisting national stakeholders in determining the ideal annual pediatric workforce that would serve the need of the different European child healthcare systems.

More research is needed on the use of probiotics for critically ill patients

We are grateful to Williams and Kumar Angurana (1) for their comments on our paper (2) in Acta Paediatrica and for providing the references to their own work on the use of probiotics for critically ill patients (3,4).However, the aim of our paper was to provide guidance to primary care paediatricians and physicians who face daily questions about what probiotic strain to give patients and for what clinical indications. Therefore, we summarised the scientifically accredited guidelines and recommendations that were available on the use of probiotics in paediatric healthcare practice at the time of our study and decided not to mention every randomised controlled trial. This article is protected by copyright. All rights reserved.

P183 Urea induced ros accelerate renal failure progression

Background and aims Chronic kidney disease (CKD) in children is an irreversible process that may lead to end-stage renal disease (ESRD). Uremic toxins have been suggested to promote progression of chronic renal failure. Urea has been long considered to have negligible toxicity in patients with CKD. In contrast, a consistent number of in vitro and in vivo studies have recently shown a direct toxicity of urea. Here we investigate the hypothesis that concentrations of urea associated with CKD and increased ROS production in adipocytes and endothelial cells might also increase ROS production directly in human podocytes, causing abnormalities which promote the progression of kidney damages Methods Human conditionally immortalised podocytes were cultured in the presence or absence of 20u2009mM urea. Results Urea at concentrations usually seen in CKD, induce mitochondrial ROS production in cultured human podocytes, leading to cellular dysfunctions typically seen in the CKD progression. Urea induced ROS decrease nephrin and podocine expression (markers of renal function), increase p65 and MCP-1 expression (markers of inflammation), and increase the intracellular lipid synthesis, as shown by the increased expression and activity of the transcription factor SERBP1. Normalisation of mitochondrial ROS production prevents each of these effects of urea. In uremic mice, treatment with MnTBAP prevents the progression of renal failure. Conclusions Taken together, these data suggest that urea itself contributes to the progression of renal failure Since urea’s effects are caused by its capacity to induce mitochondrial ROS production, reduction in the high morbidity and mortality caused by ESRD may be achieved by novel therapeutics that directly target urea-induced ROS.