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Urea Cycle01:23

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The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
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The acid-base reaction class has been studied for quite some time. In 1680, Robert Boyle reported traits of acid solutions that included their ability to dissolve many substances, to change the colors of certain natural dyes, and to lose these traits after coming in contact with alkali (base) solutions. In the eighteenth century, it was recognized that acids have a sour taste, react with limestone to liberate a gaseous substance (now known to be CO2), and interact with alkalis to form neutral...
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Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
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In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
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In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
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Related Experiment Video

Updated: May 2, 2026

State of the Art Cranial Ultrasound Imaging in Neonates
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L-Citrulline in Neonates: From Bench to Bed Side.

Dwayne Mascarenhas1, Atefeh Mohammadi2,3, Randa Higazy3

  • 1Division of Neonatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Children (Basel, Switzerland)
|January 25, 2025
PubMed
Summary

L-citrulline (L-CIT) shows promise for treating neonatal conditions like necrotizing enterocolitis and bronchopulmonary dysplasia. Supplementation may reduce inflammation and oxidative stress, but further studies are needed for clinical application.

Keywords:
L-arginineL-citrullinebronchopulmonary dysplasianecrotizing enterocolitisnitric oxidepulmonary hypertension

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Area of Science:

  • Neonatal Medicine
  • Biochemistry
  • Pharmacology

Background:

  • Endothelial dysfunction, marked by low nitric oxide (NO) synthesis, contributes to neonatal diseases like necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD) with pulmonary hypertension (PH).
  • Preterm infants have immature antioxidant systems, leading to oxidative stress and damage, which impairs NO production.

Purpose of the Study:

  • To review the current evidence on L-citrulline (L-CIT) supplementation for treating neonatal NEC and BPD-associated PH.
  • To explore the potential anti-inflammatory and antioxidant roles of L-CIT in neonatal critical care.

Main Methods:

  • Review of existing literature on L-CIT supplementation in neonatal conditions.
  • Analysis of animal studies (rodent and piglet models) investigating L-CIT effects on pulmonary vasculature, alveolar growth, and inflammation.
  • Examination of pharmacokinetic data regarding L-CIT safety and tolerability in neonates.

Main Results:

  • Animal studies demonstrated that L-CIT supplementation mitigated pulmonary vascular changes, preserved alveolar growth, and reduced inflammation in models of NEC and BPD-PH.
  • L-CIT exhibited anti-inflammatory and antioxidant effects in preclinical models.
  • Pharmacokinetic data suggest L-CIT doses of 100-300 mg/kg/day are safe and well-tolerated in neonates.

Conclusions:

  • L-citrulline (L-CIT) supplementation shows potential therapeutic benefits for neonatal conditions involving endothelial dysfunction, inflammation, and oxidative stress.
  • While preclinical data and safety profiles are encouraging, large-scale clinical trials are necessary to confirm the efficacy of L-CIT in extremely preterm infants with NEC and BPD ± PH.