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J Neu

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Localization of rat small intestine glutamine synthetase using immunofluorescence and in situ hybridization.

Glutamine is an important energy source for small intestinal epithelial enterocytes and serves as a key precursor for de novo synthesis of purines and pyrimidines in these rapidly dividing cells. Although glutamine synthetase (GS) is known to be the major enzyme of glutamine biosynthesis, the precise localization of this enzyme in the small intestine is not known. Because glutamine is an important precursor for nucleic acids biosynthesis, we hypothesized that GS is preferentially expressed in the crypt region, which contains the rapidly proliferating cells in the small intestine. Accordingly, immunofluorescence with a specific polyclonal antibody and in situ hybridization using a riboprobe were performed to localize GS protein and mRNA, respectively, in adult rats. Both GS protein and GS mRNA were detected primarily in the crypt region. This finding suggests that GS is located in the region with the highest nucleotide synthesis and cell proliferation. This finding is in support of the use of parenteral glutamine in patients with severe mucosal injury affecting the crypts.

Animals↗

Enteral glutamine supplementation for very-low-birth-weight infants decreases hospital costs.

BACKGROUND: There is growing evidence that glutamine may be a conditionally essential amino acid for critically ill patients, including preterm infants cared for in neonatal intensive care units (NICUs). In a randomized study of 68 very-low-birth-weight (VLBW) infants, we found evidence of lower morbidity in a group fed glutamine-supplemented preterm infant formula from postnatal day 3 to day 30 than in a group fed a standard formula. We report here the effects of the glutamine supplementation on hospital costs in these infants. METHODS: The costs were analyzed by log-rank tests and Kaplan-Meier plots. RESULTS: The median costs for hospitalization, radiology, pharmacy, laboratory, and the NICU, and the median number of utilization units were reduced with glutamine supplementation. CONCLUSIONS: This study provides the first evidence for decreased hospital costs in VLBW neonates who receive enteral glutamine supplementation.

Birth Weight↗

Glutamine synthetase: a key enzyme for intestinal epithelial differentiation?

BACKGROUND: We have previously shown that glutamine synthetase protein and mRNA are concentrated in the crypt region of the rat small intestine and that the activity of this enzyme is highest around the time of weaning. This anatomical location and time of peak activity are sites and periods of active enterocyte differentiation. This led to our current hypothesis that glutamine synthetase is important in the differentiation of enterocytes. METHODS: To test our hypothesis, we treated Caco-2 cells with physiologic (0.6 mM) glutamine concentrations in cell culture medium. The experimental group was treated with methionine sulfoximine, an irreversible glutamine synthetase inhibitor, and the control group with phosphate buffered saline. Three standard and well-defined markers of intestinal differentiation-sucrase-isomaltase activity, microvillus formation, and electrical impedance in transwell plates-were compared between the two groups. RESULTS: The methionine-sulfoximine-inhibited group was found to have lower sucrase-isomaltase activity, a lower density of microvilli, and lower electrical impedance values over time compared with the control group. CONCLUSION: The experimental group was found to be less differentiated by all three markers of differentiation. Therefore, glutamine synthetase is important for Caco-2 cell differentiation.

Caco-2 Cells↗

Necrotizing enterocolitis: pathophysiology and prevention.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in the neonatal intensive care unit. It is a disease of medical progress in that more very low-birth-weight neonates are surviving than ever before and are thus susceptible to this potentially devastating disease. NEC received very little attention in the literature before the 1970s but now is well known to all neonatologists and pediatric surgeons. The 1500 to 2000 infants that die every year from this disease in the United States and the large number of infants who develop short gut syndrome from this disease only represent the tip of the iceberg of the problems NEC causes. The widespread fear of NEC among neonatologists and pediatric surgeons has contributed in large part to the use of the IV route rather than the gastrointestinal tract for nourishing these infants for relatively long periods. The consequences of this include a high incidence of sepsis, high hospital costs, and potential long-term neurodevelopmental disability because of poor nutrition during a very vulnerable period of growth and development. The purpose of this review is to provide a brief overview of the clinical presentation and current treatment for NEC, then provide a discussion of the pathophysiology on which strategies for prevention can be formulated.

Enteral Nutrition↗

Glutamine supplementation in low-birth-weight infants: mechanisms of action.

Very low-birth-weight infants have minimal endogenous nutritional reserves and are at high risk for stresses that induce further breakdown of these diminished reserves. They frequently receive very little glutamine because enteral feedings are often delayed and glutamine is not included in parenteral nutrition. Here we describe studies of glutamine supplementation in very low-birth-weight infants and discuss potential mechanisms for the beneficial effects.

Cross Infection↗