Pubmed-entry ::= {
pmid 21946914,
medent {
em std {
year 2011,
month 12,
day 14
},
cit {
title {
name "Recombinant human milk fat globule-EGF factor 8 produces
dose-dependent benefits in sepsis."
},
authors {
names ml {
"Shah KG",
"Wu R",
"Jacob A",
"Molmenti EP",
"Nicastro J",
"Coppa GF",
"Wang P"
},
affil str "Department of Surgery, Hofstra North Shore-LIJ School of
Medicine, 350 Community Drive, Manhasset, NY 11030, USA."
},
from journal {
title {
iso-jta "Intensive Care Med",
ml-jta "Intensive Care Med",
issn "1432-1238",
name "Intensive care medicine"
},
imp {
date std {
year 2012,
month 1
},
volume "38",
issue "1",
pages "128-136",
language "eng",
pubstatus ppublish,
history {
{
pubstatus received,
date std {
year 2010,
month 10,
day 29
}
},
{
pubstatus accepted,
date std {
year 2011,
month 8,
day 2
}
},
{
pubstatus aheadofprint,
date std {
year 2011,
month 9,
day 23
}
},
{
pubstatus other,
date std {
year 2011,
month 9,
day 28,
hour 6,
minute 0
}
},
{
pubstatus pubmed,
date std {
year 2011,
month 9,
day 29,
hour 6,
minute 0
}
},
{
pubstatus medline,
date std {
year 2012,
month 4,
day 21,
hour 6,
minute 0
}
}
}
}
},
ids {
doi "10.1007/s00134-011-2353-7",
pubmed 21946914
}
},
abstract "PURPOSE: Animal milk fat globule-EGF factor 8 (MFG-E8) has been
shown to be beneficial in attenuating the inflammatory response in sepsis. In
this study, we examined the effect of recombinant human MFG-E8 (rhMFG-E8) in
an animal model of sepsis in an effort to develop it as a potential therapy
against sepsis in humans. METHODS: Rats were subjected to sepsis by cecal
ligation and puncture (CLP), and at 5 h post-CLP, they were given different
doses of rhMFG-E8 (20, 40, 80, 160 mug/kg BW) in normal saline. At 20 h
post-CLP, samples were collected for further analysis. A 10-day survival
study was also performed. RESULTS: At 20 h after CLP, organ injury
indicators, serum IL-6 and TNF-alpha, and plasma HMGB-1 levels were
significantly increased as compared to sham-operated animals. Treatment with
20 mug/kg rhMFG-E8 significantly reduced these levels. With higher doses,
further reductions in AST and ALT (59-62%), creatinine (65-68%), and lactate
(46-57%), and serum IL-6 and TNF-alpha were obtained. The 160 mug/kg dose
produced the greatest reduction in serum TNF-alpha. With treatment with 20
mug/kg rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham
values. In a 10-day survival study, vehicle-treated animals produced a 36%
survival rate, while rhMFG-E8 significantly improved the survival rate to
68-72%. Treatment with increasing doses of rhMFG-E8 significantly reduced the
number of apoptotic cells detected and markedly attenuated the tissue damages
observed in the lungs. CONCLUSIONS: These data suggest that recombinant human
MFG-E8 is beneficial in ameliorating sepsis in an animal model of sepsis.",
mesh {
{
term "Animals"
},
{
term "Antigens, Surface",
qual {
{
subh "administration & dosage"
},
{
mp TRUE,
subh "pharmacology"
},
{
subh "therapeutic use"
}
}
},
{
term "Biological Markers",
qual {
{
subh "blood"
}
}
},
{
term "Dose-Response Relationship, Drug"
},
{
term "Glycolipids",
qual {
{
mp TRUE,
subh "therapeutic use"
}
}
},
{
term "Glycoproteins",
qual {
{
mp TRUE,
subh "therapeutic use"
}
}
},
{
term "HMGB1 Protein",
qual {
{
subh "drug effects"
}
}
},
{
term "Humans"
},
{
term "Interleukin-6",
qual {
{
subh "metabolism"
}
}
},
{
term "Male"
},
{
term "Milk Proteins",
qual {
{
subh "administration & dosage"
},
{
subh "pharmacology"
},
{
mp TRUE,
subh "therapeutic use"
}
}
},
{
term "Rats"
},
{
term "Rats, Sprague-Dawley"
},
{
term "Recombinant Proteins",
qual {
{
mp TRUE,
subh "therapeutic use"
}
}
},
{
term "Sepsis",
qual {
{
mp TRUE,
subh "drug therapy"
},
{
subh "pathology"
}
}
},
{
term "Survival Analysis"
},
{
term "Tumor Necrosis Factor-alpha",
qual {
{
subh "drug effects"
}
}
}
},
substance {
{
type nameonly,
name "Antigens, Surface"
},
{
type nameonly,
name "Biological Markers"
},
{
type nameonly,
name "Glycolipids"
},
{
type nameonly,
name "Glycoproteins"
},
{
type nameonly,
name "HMGB1 Protein"
},
{
type nameonly,
name "Interleukin-6"
},
{
type nameonly,
name "Mfge8 protein, mouse"
},
{
type nameonly,
name "Milk Proteins"
},
{
type nameonly,
name "Recombinant Proteins"
},
{
type nameonly,
name "Tumor Necrosis Factor-alpha"
},
{
type nameonly,
name "milk fat globule"
}
},
idnum {
"R01GM053008/GM/NIGMS NIH HHS",
"R01GM057468/GM/NIGMS NIH HHS"
},
pmid 21946914,
pub-type {
"Journal Article",
"Research Support, N.I.H., Extramural"
},
status medline
}
}
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