Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis.

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.

Vitamin B12 deficiency with intrinsic factor antibodies in an infant with poor growth and developmental delay.

Vitamin B12 deficiency is very rare in infants and may lead to serious hematological and neurodevelopmental abnormalities. The present article describes a case involving a seven-month-old boy with severe vitamin B12 deficiency, likely caused by juvenile pernicious anemia, an entity rarely described. The child presented with feeding intolerance, poor growth and developmental delay. He was noted to have macrocytic anemia, a markedly low serum vitamin B12 level, and elevated homocysteine and methylmalonic acid levels. Antibodies to intrinsic factor were positive. The mother was healthy, with normal vitamin B12 status. Therapy with vitamin B12 supplements led to excellent recovery of symptoms. Vitamin B12 deficiency should be considered in children presenting with failure to thrive, especially when compounded with neurological symptoms. Early diagnosis and adequate treatment is essential to avoid serious complications.

La carence en vitamine B12, très rare chez les nourrissons, peut causer de graves anomalies hématologiques et neurodéveloppementales. Le présent article expose le cas d'un garçon de sept mois ayant une grave carence en vitamine B12, probablement causée par une anémie pernicieuse juvénile, une entité rarement décrite. L'enfant présentait une intolérance alimentaire et un retard de croissance et de développement. Il avait une anémie macrocytaire, un très faible taux de vitamine B12 dans le sérum et des taux élevés d'homocystéine et d'acide méthylmalonique. Les anticorps du facteur intrinsèque étaient positifs. La mère était en bonne santé et son statut de vitamine B12 était normal.Un traitement aux suppléments de vitamine B12 a donné lieu à une excellente résorption des symptômes. Il faut envisager une carence en vitamine B12 chez les enfants ayant un retard staturopondéral, surtout en présence de symptômes neurologiques. Il est essentiel de poser rapidement un diagnostic et d'amorcer un traitement pertinent pour éviter de graves complications.

Investigating the importance of clinical topics for developing a curriculum on gastroenterology for pediatric residents.

BACKGROUND: Focused objectives provide effective learning. Pediatric residents in Canada follow objectives set by the Royal College of Physicians and Surgeons of Canada (RCPSC) with the goal of becoming competent general pediatricians. During the gastroenterology rotation, it remains unclear as to what clinical problems listed in the aforementioned objectives are crucial to understand as part of general pediatric practice. The purpose of this study was to identify the gastroenterological conditions of most importance to incorporate into a focused curriculum for pediatric residents. METHODS: All pediatricians across four Canadian Atlantic provinces were surveyed by a mailed questionnaire. Questions included demographics and ranking of the 14 clinical problems currently listed in the RCPSC objectives along with six more generated after input was gained from pediatric gastroenterologists. RESULTS: Of the 234 pediatricians surveyed, 132 (56%) responded, 48% of whom were general pediatricians. Celiac disease, gastroesophageal reflux, and obesity (currently not on the RCPSC list) were identified as important/very important conditions to understand by 94.4%, 96.1%, and 96.0% of respondents, respectively. There were no significant differences in rankings between general pediatricians and subspecialists. A large majority recommended that a rotation in gastroenterology be mandatory during pediatric residency. CONCLUSIONS: Pediatricians from four Canadian Atlantic provinces recommended a list of gastrointestinal conditions to be included in pediatric residency training. It would be important to consider these recommendations to keep the training curriculum in sync with real world needs.

CONTEXTE: L'établissement d'objectifs ciblés favorise un apprentissage efficient. Au Canada, les résidents en pédiatrie poursuivent les objectifs fixés par le Collège royal des médecins et des chirurgiens du Canada (CRMCC) pour devenir de bons pédiatres généralistes. Durant le stage en gastro-entérologie, les problèmes cliniques à prioriser dans cette liste d'objectifs, en vue d'une pratique pédiatrique générale, demeurent imprécis pour les résidents. Cette étude visait à identifier les troubles de l'appareil digestif les plus importante à inclure à un cursus ciblé à l'intention des résidents en pédiatrie. MÉTHODOLOGIE: On a mené un sondage auprès de pédiatres des quatre provinces de l'Atlantique en leur envoyant un questionnaire par la poste. Les questions visaient à obtenir des données démographiques et leur demander de classer 14 troubles faisant actuellement partie de la liste du CRMCC, puis six autres après avoir recueilli des avis auprès de gastro-entérologues pédiatriques. RÉSULTATS: 132 (56 %) des 234 pédiatres sondés, dont 48 % étaient des pédiatres généralistes, ont répondu au questionnaire. La maladie cœliaque, le reflux gastro-œsophagien et l'obésité (maladie qui ne figure pas actuellement sur la liste du CRMCC) ont été jugés comme des troubles importants ou très importants à connaître par 94,4 %, 96,1 % et 96,0 % des répondants, respectivement. On n'a observé aucune différence significative entre le classement des pédiatres généralistes et celui des surs-spécialistes. Une grande majorité de répondants ont recommandé qu'un stage en gastro-entérologie devienne obligatoire durant la résidence en pédiatrie. CONCLUSIONS: Les pédiatres des quatre provinces de l'Atlantique ont recommandé une liste de troubles de l'appareil digestif à inclure au programme de résidence en pédiatrie. Il serait important de tenir compte de ces recommandations pour que le programme de formation reste adapté aux besoins de la réalité.