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Yokohama-shi, Japan

Awazu M.,Keio University | Hida M.,Keio University | Hida M.,Perinatal Center
Pediatric Research | Year: 2015

Background:Maternal nutrient restriction produces offspring with fewer nephrons. We studied whether the reduced nephron number is due to the inhibition of ureteric branching or early cessation of nephrogenesis in rats. Signaling pathways involved in kidney development were also examined.Methods:The offspring of dams given food ad libitum (control (CON)) and those subjected to 50% food restriction (nutrient restriceted (NR)) were examined.Results:At embryonic day 13 (E13), there was no difference between NR and CON in body weight or kidney size. Ureteric buds branched once in both NR and CON. At E14 and E15, body and kidney size were significantly reduced in NR. Ureteric bud tip numbers were also reduced to 50% of CON. On the other hand, the disappearance of nephrogenic zone and a nephron progenitor marker Cited1 was not different between CON and NR. The final glomerular number of NR was 80% of CON. Activated extracellular signal-regulated kinase (ERK), p38, PI3K, Akt, and mammallian target of rapamycin (mTOR), and protein expression of β-catenin were downregulated at E15.Conclusion:Ureteric branching is inhibited and developmentally regulated signaling pathways are downregulated at an early stage by maternal nutrient restriction. These changes, not early cessation of nephrogenesis, may be a mechanism for the inhibited kidney growth and nephrogenesis. © 2015 International Pediatric Research Foundation, Inc.


Savman K.,Gothenburg University | Savman K.,Perinatal Center | Heyes M.P.,National Institute of Mental Health | Svedin P.,Gothenburg University | Karlsson A.,Gothenburg University
Translational Stroke Research | Year: 2013

Activation of microglia/macrophages is important in neonatal hypoxic-ischemic (HI) brain injury. Based on experimental studies, we identified macrophage/microglia-derived mediators with potential neurotoxic effects after neonatal HI and examined them in cerebrospinal fluid (CSF) from newborn infants after birth asphyxia. Galectin-3 is a novel inflammatory mediator produced by microglia/macrophages. Galectin-3 is chemotactic for inflammatory cells and activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase resulting in production and release of reactive oxygen species (ROS). Matrix metalloproteinase-9 (MMP-9) is a tissue-degrading protease expressed by activated microglia in the immature brain after HI. Both galectin-3 and MMP-9 contribute to brain injury in animal models for neonatal HI. Quinolinic acid (QUIN) is a neurotoxic N-methyl-d-aspartate (NMDA) receptor agonist also produced by activated microglia/macrophages. Galectin-3 and MMP-9 were measured by ELISA and QUIN by mass spectrometry. Asphyxiated infants (n = 20) had higher levels of galectin-3 (mean (SEM) 2. 64 (0. 43) ng/mL) and QUIN (335. 42 (58. 9) nM) than controls (n = 15) (1. 36 (0. 46) ng/mL and 116. 56 (16. 46) nM, respectively), p & 0. 05 and p & 0. 01. Infants with septic infections (n = 10) did not differ from controls. Asphyxiated infants with abnormal outcome had higher levels of galectin-3 (3. 96 (0. 67) ng/mL) than those with normal outcome (1. 76 (0. 32) ng/mL), p = 0. 02, and the difference remained significant in the clinically relevant group of infants with moderate encephalopathy. MMP-9 was detected in few infants with no difference between groups. The potentially neurotoxic macrophage/microglia-derived mediators galectin-3 and QUIN are increased in CSF after birth asphyxia and could serve as markers and may contribute to injury. © 2012 Springer Science+Business Media New York.


Sperling J.D.,Brown University | Dahlke J.D.,Perinatal Center | Sibai B.M.,Health University of Texas Medical School at Houston
American Journal of Obstetrics and Gynecology | Year: 2016

In 1946, Dr Curtis Mendelson suggested that aspiration during general anesthesia for delivery was avoidable by restricting oral intake during labor. This suggestion proved influential, and restriction of oral intake in labor became the norm. These limitations may contribute to fear and feelings of intimidation among parturients. Modern obstetrics, especially in the setting of advances in obstetric anesthesia, does not mirror the clinical landscape of Mendelson; hence, one is left to question if his findings remain relevant or if they should inform current recommendations. The use of general anesthesia at time of cesarean delivery has seen a remarkable decline with increased use of effective neuraxial analgesia as the standard of care in modern obstetric anesthesia. While the American College of Obstetricians and Gynecologists now endorses clear liquids during labor, current recommendations continue to suggest that solid food intake should be avoided. Recent evidence from a systematic review involving 3130 women in active labor suggests that oral intake should not be restricted in women at low risk of complications, given there were no identified benefits or harms of a liberal diet. Aspiration and other adverse maternal outcomes may be unrelated to oral intake in labor and as such, qualitative measures such as patient satisfaction should be paramount. It is time to reassess the impact of oral intake restriction during labor given the minimal risk of aspiration during labor in the setting of modern obstetric anesthesia practices. © 2016 Elsevier Inc. All rights reserved.


Dahlke J.D.,Perinatal Center | Mendez-Figueroa H.,University of Houston | Maggio L.,Brown University | Hauspurg A.K.,Brown University | And 3 more authors.
American Journal of Obstetrics and Gynecology | Year: 2015

Objective The purpose of this study was to compare 4 national guidelines for the prevention and management of postpartum hemorrhage (PPH). Study Design We performed a descriptive analysis of guidelines from the American College of Obstetrician and Gynecologists practice bulletin, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, the Royal College of Obstetrician and Gynaecologists (RCOG), and the Society of Obstetricians and Gynaecologists of Canada on PPH to determine differences, if any, with regard to definitions, risk factors, prevention, treatment, and resuscitation. Results PPH was defined differently in all 4 guidelines. Risk factors that were emphasized in the guidelines conferred a high risk of catastrophic bleeding (eg, previous cesarean delivery and placenta previa). All organizations, except the American College of Obstetrician and Gynecologists, recommended active management of the third stage of labor for primary prevention of PPH in all vaginal deliveries. Oxytocin was recommended universally as the medication of choice for PPH prevention in vaginal deliveries. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and RCOG recommended development of a massive transfusion protocol to manage PPH resuscitation. Recommendations for nonsurgical treatment strategies such as uterine packing and balloon tamponade varied across all guidelines. All organizations recommended transfer to a tertiary care facility for suspicion of abnormal placentation. Specific indications for hysterectomy were not available in any guideline, with RCOG recommending hysterectomy "sooner rather than later" with the assistance of a second consultant. Conclusion Substantial variation exists in PPH prevention and management guidelines among 4 national organizations that highlights the need for better evidence and more consistent synthesis of the available evidence with regard to a leading cause of maternal death. © 2015 Published by Elsevier Inc.


Hisano M.,National Center for Child Health and Development | Suzuki R.,Perinatal Center | Sago H.,National Center for Child Health and Development | Murashima A.,National Center for Child Health and Development | Yamaguchi K.,National Center for Child Health and Development
European Journal of Clinical Nutrition | Year: 2010

Iron deficiency is the most common cause of anemia in pregnancy. Pregnant women with anemia are, in general, exclusively treated with iron supplementation. We observed that several pregnant women with anemia who were nonresponsive to iron supplementation also had vitamin B6 deficiency, and that anemia in these cases improved with the administration of vitamin B6. Our prospective study in healthy pregnant women showed that blood levels of iron, ferritin and vitamin B6, in particular, fell to the lower limit of the nonpregnant reference range by the third trimester. We conclude that it is important to take into account the deficiency of vitamin B6 besides iron in the evaluation of anemia during pregnancy. © 2010 Macmillan Publishers Limited All rights reserved.

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