GASTROENTEROLOGY & GI SURGERY •
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#7
In the nation by U.S. News & World Report
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Board-certified pediatric
gastroenterologists and hepatologists
$4.5M+
Annual research funding
inflammatory pathways in the liver and activating
receptor signaling, promoting injury to the liver
cell along with cholestasis, cell death and necrosis.
But this alone was not enough to explain the
damage done to the liver. They also proposed that
there was something in the intravenous nutrition
that synergized with the intestinal failure to cause
liver injury. The lipid problem
To study this phenomenon, they induced
intestinal injury and increased permeability in
a mouse model using dextran sulphate sodium
followed by a continuous infusion of soy-based
lipid parenteral nutrition through a central
venous catheter. They found that they could
cause cholestasis and liver injury, but only with
the combination of both intestinal injury and
TPN infusion. Around the same time, other physicians were
taking different approaches: reducing the lipids in
TPN, switching to fish oil-based IV lipids and using
a newer preparation called SMOF – a combination
of soy, fish and other oils.
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The team of researchers then used their model to
demonstrate the part played by TPN, combining
evidence coming out of other research centers
to prove that the lipid component of TPN —
plant sterols in particular — was a major factor
responsible for PNAC.
“Lipid modification discovered in Boston was a
big breakthrough, and our model verifies that
modifying lipids from soy-based emulsions to fish
oil-based emulsions, or reducing the lipid amount,
is a good thing for the liver,” says Dr. Sokol. “There’s
a clear link but we believe that we can improve
treatment even further, without reducing the
amount of brain-building lipids that infants receive.”
By now, Dr. Sokol and his team were narrowing
in on the role of hepatic macrophages, which
they hypothesized may be triggered by plant
sterol containing lipid emulsions and gut-derived
products to release cytokines that directly
suppress bile and sterol transporters in the liver,
causing cholestasis.
Basically, the sterols were stuck.
If they could further understand the mechanism of
the injury, there could be other therapies that would
still allow infants to get all the lipids they need.
LEADERSHIP:
Ronald Sokol, MD
Chief, Pediatric Gastroenterology,
Hepatology and Nutrition,
The Arnold Silverman, MD,
Endowed Chair in Digestive Health
For gastroenterology healthcare
professional resources, visit
childrenscolorado.org/DigestiveHCP.
For that, they combined genetic, molecular
and pharmacological approaches to distill the
role of the signaling pathways that control bile
NEW CONSTELLATIONS
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