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Title
Harry M. Vars award. Glutamine or fiber supplementation of a
defined formula diet: impact
on bacterial translocation, tissue composition, and response
to endotoxin.
Author
Barber AE; Jones WG 2d; Minei JP; Fahey TJ 3d; Moldawer LL; Rayburn
JL; Fischer E;
Keogh CV; Shires GT; Lowry SF
Source
JPEN J Parenter Enteral Nutr, 1990 Jul, 14:4, 335-43
Abstract
Despite provision of adequate calories, defined formula diets
in rats lead to bacterial
translocation (BT), fatty infiltration of the liver, and an increased
susceptibility to endotoxin.
These deleterious effects may be due in part to a loss of intestinal
barrier integrity resulting
from bowel atrophy. Defined formula diets lack both glutamine
and fiber, substances which
may help maintain intestinal mass. To determine whether supplementation
of defined
formula diets with either glutamine or fiber might prevent bowel
atrophy and, thus, BT,
hepatic steatosis, and the altered response to endotoxin, Wistar
rats were fed (1) defined
formula diet ad libitum (DFD), (2) (DFD + 2% (w/v) glutamine,
(GLUT), or (3) DFD +
2% (w/v) psyllium (FIBER). Rats given standard food isocalorically
pair-fed to DFD were
used as controls. Nutritional status was assessed by daily weight
gain, as well as the ability
to maintain serum albumin, hematocrit and white blood counts.
After 2 weeks of these
feeding regimens, animals were sacrificed, and organ weights
and composition were
determined, with rates of bacterial translocation determined
by mesenteric lymph node,
abdominal viscera, and cecal cultures. Additional animals receiving
the same experimental
diets were subsequently challenged with endotoxin and observed
for mortality with rates of
post-endotoxin BT and the responses of acute phase proteins and
cytokines measured. All
dietary regimens resulted in equivalent weight gain and other
nutritional parameters. Both
glutamine and fiber supplementation maintained small bowel mass,
but only GLUT
preserved normal jejunal mucosal architecture. Neither fiber
nor glutamine supplementation
prevented cecal bacterial overgrowth or BT, resulting from the
DFD.(Abstract
TRUNCATED AT 250 WORDS)
Title
Glutamine prevents parenteral nutrition-induced increases in
intestinal permeability [see
comments]
Author
Li J; Langkamp Henken B; Suzuki K; Stahlgren LH
Source
JPEN J Parenter Enteral Nutr, 1994 Jul, 18:4, 303-7
Abstract
In addition to its role in absorbing nutrients, the intestinal
mucosa provides an important
barrier against toxins and bacteria in the bowel lumen. This
study evaluated changes in rat
jejunal permeability and histology after total parenteral nutrition
(TPN) or TPN
supplemented with glutamine. Lactulose and mannitol were used
to measure jejunal
permeability, and fixed stained histologic specimens were used
to measure mucosal
dimensions. After the insertion of central venous catheters,
18 male rats were randomly
divided into three groups: CHOW, saline infusion with a standard
laboratory rat diet ad
libitum; TPN; and GLN, 2% L-glutamine-supplemented TPN. The TPN
and GLN groups
received isocaloric, isovolumic, and isonitrogenous feedings.
After 7 days of infusion, a
laparotomy was performed, and lactulose and mannitol were instilled
into the lumen of a
25-cm ligated segment of jejunum. Urine was collected for 5 hours
and assayed for
lactulose, mannitol, and creatinine. The jejunum was harvested,
and wet weight, villus
height, mucosal thickness, and villus width were measured. Intestinal
permeability to
lactulose and the lactulose to mannitol ratio significantly increased
after TPN compared with
CHOW, and these effects were prevented with the addition of glutamine
to the TPN
solution. Jejunal villus height and mucosal thickness significantly
decreased following TPN
but were not significantly different from CHOW when glutamine
was added to the TPN
solution. These data suggest that TPN was associated with increased
jejunal permeability
and that glutamine, when added to the TPN solution, prevented
this effect. In addition,
glutamine reduced TPN-associated atrophy of the jejunum.
Title
Gut glutamine metabolism.
Author
Souba WW; Herskowitz K; Salloum RM; Chen MK; Austgen TR
Address
Department of Surgery, University of Florida College of Medicine,
Gainesville.
Source
JPEN J Parenter Enteral Nutr, 1990 Jul, 14:4 Suppl, 45S-50S
Abstract
The gut plays a key role in interorgan glutamine metabolism in
normal and catabolic states.
During critical illness, the gut responds to prevailing metabolic
pressures that may result in a
temporary "reset" in interorgan glutamine flow. As
the body recovers from the disease
process, the alterations in gut glutamine metabolism revert to
normal, which helps restore
glutamine homeostasis. Overwhelming stresses, such as severe
systemic infection, may
lead to permanent organ dysfunction and further adaptive changes
in glutamine metabolism.
Title
The effects of glutamine on intestinal epithelial cell proliferation
in parenterally fed rats.
Author
Mandir N; Goodlad RA
Address
Histopathology Unit, Imperial Cancer Research Fund, 44 Lincoln's
Inn Fields, London
WC2A 3PX, UK.
Source
Gut, 1999 May, 44:5, 608-14
Abstract
BACKGROUND: Several papers have indicated that glutamine is a
preferred fuel for the
enterocyte and that it can increase intestinal epithelial cell
proliferation. AIMS: To investigate
the effects of glutamine on intestinal epithelial cell proliferation
in the parenterally fed rat.
METHODS: Five groups of six rats were fed parenterally; a group
of orally fed rats was
also studied. Crypt cell proliferation was studied after six
days using native mitoses in
microdissected crypts and bromodeoxyuridine labelling. RESULTS:
No effect of treatment
was seen on intestinal weight; however, the weights of the small
intestine, caecum, and
colon were all significantly heavier in the orally fed group
than in the total parenteral
nutrition groups (p<0.001). There was no effect of any of
the glutamine treatments on
mitotic activity in the small intestine. In the colon there was
a small increase in native
mitoses with glutamine (p=0.03). There was also an indication
of increased proliferative
activity in the first fifth of the small intestine and colon
with glutamine. Little effect of
glutamine on bromodeoxyuridine labelling in either site was observed,
but there was a small
but significant reduction in growth fraction of the colon of
the glutamine treated group. The
labelling distribution curve from sections and the mitotic distribution
curve obtained from
crypt squashes showed a good correlation. CONCLUSION: Glutamine
has a small, but
significant effect on mitotic activity but only in the colon.
Modest effects on the distribution
of labelled cells were also seen.
Title
Distribution of glutaminase and glutamine synthetase activities
in the human gastrointestinal
tract.
Author
James LA; Lunn PG; Middleton S; Elia M
Source
Clin Sci (Colch), 1998 Mar, 94:3, 313-9
Abstract
1. The activities of the two key enzymes involved in glutamine
metabolism, glutaminase
and glutamine synthetase, were measured in mucosal biopsies taken
from different sites
throughout the human gastrointestinal tract, from oesophagus
to rectum. 2. The specific
activity of glutamine synthetase was highest in the stomach (4.5
nmol glutamine formed per
minute per mg of protein), but both small and large intestine
and the oesophagus had little
synthesizing capacity (less than 0.3 nmol of glutamine formed
per minute per mg of
protein). 3. Glutaminase specific activity was highest in the
small intestine (53 nmol
glutamate formed per minute per mg of protein by duodenal mucosa),
intermediate in the
large intestine and lowest in the oesophagus and stomach (less
than 13 nmol of glutamate
formed per minute per mg of protein). 4. The glutamine concentration
in the mucosa was
lower in the duodenum than in the colon (0.62 and 0.95 mmol/kg
wet weight respectively),
but both were much lower than the measured K(m) values of glutaminases
obtained from
these sites (3.8 and 4.0 nmol/kg wet weight respectively). 5.
The concentration of glutamine
in saliva, stomach juice, bile and duodenal juice suggests that
very little glutamine passes
into the gastrointestinal tract via these secretions. 6. The
study provides the most complete
information on the distribution of glutamine synthetase and glutaminase
along the human
gastrointestinal tract, and suggests that (i) both the small
and large intestines have a high
potential for glutamine metabolism, but little synthesizing capacity,
thus both must derive
their glutamine from other sources, and (ii) neither the stomach
nor the oesophagus have a
high glutaminase activity, although the stomach has substantial
capacity to synthesize
glutamine. The distribution of the enzymes along the gastrointestinal
tract may help
rationalize the use of glutamine for treating diseases that affect
different parts of the
gastrointestinal tract.
Title
Glutamine reduces bacterial translocation after small bowel transplantation
in
cyclosporine-treated rats.
Author
Zhang W; Frankel WL; Bain A; Choi D; Klurfeld DM; Rombeau JL
Source
J Surg Res, 1995 Feb, 58:2, 159-64
Abstract
Bacterial translocation (BT) of enteric organisms is a major
cause of sepsis in patients
undergoing small bowel transplantation (SBT). Cyclosporine (CsA)
may be toxic to
intestinal epithelium and increase the risk of BT. Glutamine
(Gln) is the preferred enterocyte
fuel and maintains graft epithelial integrity in experimental
SBT. This study determined the
effects of CsA on mucosal structure and function of transplanted
intestinal isograft and
examined whether Gln-enriched diet reversed CsA-induced intestinal
toxicity. Thirty-three
adult Lewis rats underwent resection of the distal 60% of small
bowel and received an
orthotopic jejunal isograft. Rats received either elemental diet
with 2% Gln or the same diet
with balanced nonessential amino acids (non-Gln) by gastrostomy
for 10 days. CsA (15
mg/kg, im) or olive oil was injected daily. Rats were assigned
to four groups: non-Gln with
vehicle, non-Gln with CsA, Gln with vehicle, and Gln with CsA.
Mucosal villous height,
surface area, crypt depth, 14C glucose absorption, BT to mesenteric
lymph nodes (MLN),
and body weight change were evaluated. The non-Gln with CsA group
had the highest
incidence of BT (P < 0.001). Gln groups had significantly
decreased BT (P < 0.01) and
increased crypt depth and villous surface area (P < 0.01)
when compared to non-Gln
groups. Body weight significantly decreased in CsA groups when
compared to non-CsA
groups (P < 0.01). These results indicate at CsA significantly
decreased body weight and
increased BT without decreasing mucosal structure and glucose
absorption of intestinal
isografts.(Abstract TRUNCATED AT 250 WORDS)
Title
Glutamine nutrition and requirements.
Author
Smith RJ; Wilmore DW
Source
JPEN J Parenter Enteral Nutr, 1990 Jul, 14:4 Suppl, 94S-99S
Abstract
Glutamine is the most abundant free amino acid in plasma and
tissue pools and an
important intermediate in a number of metabolic pathways. Glutamine
levels decline
markedly in the course of many different catabolic disease states
and it has recently been
suggested that glutamine may be a conditionally essential dietary
nutrient rather than a
nonessential amino acid. Changes in tissue glutamine concentrations
have been shown to
correlate with net protein turnover, and there is evidence that
glutamine may both stimulate
protein synthesis and inhibit protein degradation. In experimental
animals, we have shown
that the fall in glutamine concentrations in plasma and tissue
pools that occurs in the
postoperative state can be prevented or reversed by providing
large quantities of exogenous
glutamine. In gastrointestinal tissues, the provision of glutamine-free
total parenteral
nutrition solutions is associated with atrophy of mucosal cells
and pancreatic exocrine cells.
Glutamine-supplemented parenteral formulas result in diminished
atrophy of intestinal
mucosal and pancreatic exocrine cells; both intravenous and enteral
glutamine promote
gastrointestinal tissue regeneration following toxic injury.
In animals undergoing partial
small intestine resection, glutamine feeding leads to increased
adaptive hyperplasia in
remaining intestinal segments and results in earlier postoperative
weight gain. All of these
trophic, anabolic effects of glutamine require the administration
of quantities that exceed the
glutamine content of normal dietary protein. These findings in
experimental animals support
the hypothesis that glutamine is a conditionally essential nutrient
and suggest a potentially
important role for glutamine-supplemented nutrition in catabolic
disease states.
Title
Effects of glutamine supplements and radiochemotherapy on systemic
immune and gut
barrier function in patients with advanced esophageal cancer.
Author
Yoshida S; Matsui M; Shirouzu Y; Fujita H; Yamana H; Shirouzu
K
Source
Ann Surg, 1998 Apr, 227:4, 485-91
Abstract
OBJECTIVE: The objective of this study was to determine whether
oral glutamine
supplements can protect lymphocyte and gut barrier function in
patients with advanced
esophageal cancer undergoing radiochemotherapy. SUMMARY BACKGROUND
DATA:
Glutamine supplements improved protein metabolism in tumor bearing
rats who underwent
chemotherapy and reduced the toxicity of chemotherapy through
an enhancement of
glutathione production in rats. METHODS: Thirteen patients with
esophageal cancer were
randomly placed in either a control or a glutamine group. Glutamine
was administered
orally (30 g/day) at the start of radiochemotherapy and for the
subsequent 28 days. All
patients underwent mediastinal irradiation and chemotherapy consisting
of 5-fluorouracil
and cisplatin. The lymphocyte count was determined, and blast
formation was assessed after
stimulation with phytohemagglutinin and concanavalin A. Gut barrier
function was assessed
by measuring the total amount of phenolsulfonphthalein excreted
in the urine after the oral
administration of phenolsulfonphthalein. RESULTS: Glutamine supplements
prevented a
reduction in the lymphocyte count (control: 567 +/- 96/mm3 vs.
glutamine: 1007 +/- 151, p
< 0.05), and blast formation of lymphocyte (phytohemagglutinin,
control: 19478 +/- 2121
dpm vs. glutamine: 33860 +/- 1433, p < 0.01, concanavalin
A, control: 19177 +/- 1897
dpm vs. glutamine: 29473 +/- 2302, p < 0.01), and amount of
phenolsulfonphthalein
excretion in the urine was greater with control than with glutamine
group (control: 15.4 +/-
2.4% vs. glutamine: 7.4 +/- 1.2, p < 0.05) 7 days after the
initiation of radiochemotherapy.
CONCLUSIONS: Oral glutamine supplementation protects lymphocytes
and attenuates gut
permeability in patients with esophageal cancer during radiochemotherapy.
Title
Histidine and histamine metabolism in rat enterocytes.
Author
Guihot G; Blachier F
Source
Mol Cell Biochem, 1997 Oct, 175:1-2, 143-8
Abstract
To study the metabolic fate of L-histidine and histamine in rat
isolated enterocytes,
enterocytes were incubated in the presence of 0.1 mM L-[U-14C]
histidine. At the rate of
11.1 +/- 2.7 pmol/10(6) cells/30 min, the amino acid was incorporated
into cellular proteins.
80 microM cycloheximide, i.e. a protein synthesis inhibitor,
inhibited this incorporation by
70 +/- 17%. L-histidine was used for cellular protein synthesis
which depended on time and
concentration. 0.1 mM L-[U-14C] histidine was little oxidized
by intestinal cells, i.e. 0.12
+/- 0.06 pmol/10(6) cells/30 min, and was not converted into
histamine. When 10 mM
histamine was added to the incubation medium, it completely inhibited
the incorporation of
0.1 mM [1,4-14C] putrescine into isolated enterocytes. In enterocyte
homogenates, this
corresponded to inhibition by histamine of putrescine incorporation
as catalyzed by
transglutaminase activity. Since histamine incorporation into
TCA-precipitable material
derived from enterocyte homogenates depended on time and concentration,
we concluded
that exogenous, but not de novo-formed histamine was able to
compete with putrescine
incorporation into enterocytes as catalyzed by transglutaminase
activity.
Title
Glutamine preserves gut glutathione levels during intestinal
ischemia/reperfusion.
Author
Harward TR; Coe D; Souba WW; Klingman N; Seeger JM
Source
J Surg Res, 1994 Apr, 56:4, 351-5
Abstract
Intestinal ischemia/reperfusion (I/R) causes formation of reactive
oxygen intermediates
(ROI) which lead to mucosal cell injury. Glutathione (GSH), an
ROI scavenger, protects
tissues from ROI-mediated cell injury. Since GSH biosynthesis
is partially dependent on
glutamine (Gln) levels, we tested the hypothesis that intravenous
Gln infusion will assist in
maintaining mucosal cell GSH levels and decrease membrane lipid
peroxidation during
intestinal I/R. The external jugular vein of male Sprague-Dawley
rats was cannulated and
infused with normal saline (NS) at 2 cc/hr. After 3 days, matched
pairs of rats received
either NS alone or NS+ 3% Gln for an additional 24 hr. Next,
mucosal GSH levels were
measured after a sham I/R in 6 rats and after either 30 or 60
min of ischemia/60 min of
reperfusion in a group of 8 and 12 rats, respectively. Finally,
conjugated diene (CD), a
byproduct of membrane lipid peroxidation, was measured following
60 min of ischemia/60
min of reperfusion in a separate group of 12 rats. Control rats
had the highest GSH levels
and there was no difference between NS vs NS + 3% Gln rats (2.50
+/- 0.48 vs 2.50 +/-
0.43, P = NS). With 30 and 60 min of ischemia/60 min of reperfusion,
GSH levels were
significantly lower in NS-infused rats compared to those in NS
+ 3% Gln-infused rats (30
min: 1.54 +/- 0.14 vs 1.80 +/- 0.16, P < 0.05; 60 min: 1.27
+/- 0.15 vs 1.52 +/- 0.20, P <
0.04). In addition, CD levels were lower in NS + 3% Gln-infused
rats compared to those in
NS alone-infused rats (5.58 +/- 0.87 vs 7.94 +/- 0.55, P <
0.04). In conclusion, Gln
supplementation partially maintains gut GSH levels during bowel
I/R, which in turn lessens
I/R-induced cell membrane lipid peroxidation. |
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