Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome

2002 ◽  
Vol 37 (5) ◽  
pp. 765-769 ◽  
Author(s):  
J. Sham ◽  
G. Martin ◽  
J.B. Meddings ◽  
D.L. Sigalet
2017 ◽  
Vol 312 (4) ◽  
pp. G390-G404 ◽  
Author(s):  
David W. Lim ◽  
Crystal L. Levesque ◽  
Donna F. Vine ◽  
Mitsuru Muto ◽  
Jacob R. Koepke ◽  
...  

Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg−1·day−1) alone, enteral EGF-cm (80 μg·kg−1·day−1) alone, or GLP-2 and EGF-cm in combination. Adaptation was assessed by intestinal length, histopathology, Üssing chamber analysis, and real-time quantitative PCR of intestinal growth factors. Combined EGF-cm and GLP-2 treatment increased intestinal length in all three surgical models ( P < 0.01). EGF-cm alone selectively increased bowel weight per length and jejunal villus height in the JI group only. The JC group demonstrated increased intestinal weight and villus height ( P < 0.01) when given either GLP-2 alone or in combination with EGF-cm, with no effect of EGF-cm alone. Jejunal permeability of mannitol and polyethylene glycol decreased with combination therapy in both SBS groups ( P < 0.05). No difference was observed in fat absorption or body weight gain. IGF-1 mRNA was differentially expressed in JI vs. JC piglets with treatment. Combined treatment with GLP-2 and EGF-cm induced intestinal lengthening and decreased permeability, in addition to the trophic effects of GLP-2 alone. Our findings demonstrate the benefits of novel combination GLP-2 and EGF treatment for neonatal SBS, especially in the JC model representing most human infants with SBS. NEW & NOTEWORTHY Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current research shows that over and above known trophic effects, the combination of GLP-2 and EGF synergistically lengthens the bowel in neonatal piglet models of SBS. Most notable benefit occurred with resection of the terminal ileum, the common clinical anatomy seen in neonatal SBS and associated with least de novo lengthening postsurgery.


2005 ◽  
Vol 40 (5) ◽  
pp. 763-768 ◽  
Author(s):  
David L. Sigalet ◽  
Gary R. Martin ◽  
J. Decker Butzner ◽  
Andre Buret ◽  
Jonathan B. Meddings

2003 ◽  
Vol 124 (4) ◽  
pp. A430
Author(s):  
David Sigalet ◽  
Gary Martin ◽  
Jon Meddings ◽  
Andre Buret ◽  
James Hardin ◽  
...  

2000 ◽  
Vol 35 (5) ◽  
pp. 692-695 ◽  
Author(s):  
I. Eizaguirre ◽  
P. Aldazabal ◽  
M.J. Barrena ◽  
J.M. Garcia-Arenzana ◽  
C. Ariz ◽  
...  

2002 ◽  
Vol 282 (1) ◽  
pp. G156-G164 ◽  
Author(s):  
Bohuslav Dvorak ◽  
Melissa D. Halpern ◽  
Hana Holubec ◽  
Catherine S. Williams ◽  
Debra L. McWilliam ◽  
...  

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-α mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.


Peptides ◽  
2004 ◽  
Vol 25 (5) ◽  
pp. 793-801 ◽  
Author(s):  
A.J FitzGerald ◽  
M Pu ◽  
T Marchbank ◽  
B.R Westley ◽  
F.E.B May ◽  
...  

2000 ◽  
Vol 29 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Will F. Johnson ◽  
Christopher R. DiPalma ◽  
Thomas R. Ziegler ◽  
Sheila Scully ◽  
Catherine L. Farrell

1998 ◽  
Vol 114 ◽  
pp. A886 ◽  
Author(s):  
W.F. Johnson ◽  
C.R. DiPalma ◽  
T.R. Ziegler ◽  
C.L. Farrell

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