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Title
Growth hormone and glutamine do not stimulate intestinal adaptation following massive
small bowel resection in the rat.
Author

Vanderhoof JA; Kollman KA; Griffin S; Adrian TE
Source
J Pediatr Gastroenterol Nutr, 1997 Sep, 25:3, 327-31
Abstract

BACKGROUND: Certain nutrients and other trophic factors are highly sensitive stimulants
of intestinal adaptation following short bowel syndrome. Growth hormone and glutamine in
a modified diet have been shown to enhance nutrient absorption in patients with severe short
bowel syndrome. However, neither growth hormone nor glutamine is capable of enhancing
adaptation in an animal model. This study was conducted to determine if the combination of
glutamine and growth hormone could enhance gut adaptation following massive small
bowel resection in the rat. METHODS: Thirty-four male rats received 70% jejunoileal
resection. The first group received glycine and rat growth hormone, the second glutamine
and rat growth hormone, and the third glycine but no growth hormone. RESULTS: There
was no evidence that the combination of glutamine and growth hormone could enhance
mucosal mass, mucosal protein, or mucosal DNA levels relative to the other two control
groups of animals. Likewise, sucrase activities were not enhanced by glutamine and growth
hormone. CONCLUSIONS: It is unlikely that the combination of glutamine and growth
hormone will be of benefit in the treatment of patients with short bowel syndrome. The
results in previous human studies can be alternatively explained by the long-term
nonspecific effect of enteral nutrition on gut adaptation.

Title

Nutrient metabolism by gut tissues.
Author

Britton R; Krehbiel C
Source
J Dairy Sci, 1993 Jul, 76:7, 2125-31
Abstract

The gut uses a disproportionate amount of energy (about 25% of total oxygen consumption)
for the size of the tissue (about 6% of body weight). Therefore, knowledge of metabolites
used in gut tissues is important to assess nutrient needs. The VFA produced intraruminally
are used to varying degrees by rumen epithelial tissue. A review of net portal absorption
data essentially confirms earlier studies that show acetate, propionate, and butyrate
metabolism by stomach tissue to be 30, 50, and 90%, respectively, of ruminant production.
Glucose also is used by rumen epithelial tissue; however, glutamine appears to be a poor
substrate for energy production. Tissue of the small intestine uses glutamine, glucose, and
ketones but does not use VFA very well for energy. Cecal and colonic tissues can use
glucose and glutamine for energy, but butyrate is the preferred substrate in both tissues.

Title

Glutamine-enriched enteral diet enhances bacterial clearance in protected bacterial peritonitis,
regardless of glutamine form [see comments]
Author

Furukawa S; Saito H; Inaba T; Lin MT; Inoue T; Naka S; Fukatsu K; Hashiguchi Y; Han I;
Matsuda T; Ikeda S; Muto T
Source
JPEN J Parenter Enteral Nutr, 1997 Jul, 21:4, 208-14
Abstract

BACKGROUND: The effects of glutamine (Gln)-enriched enteral diets on bacterial
clearance were investigated in a rat protracted peritonitis model. The effects of the Gln form,
peptide-based vs free amino acid-based, were also compared. METHODS: Twenty-three
rats underwent gastrostomy. An osmotic pump was implanted in the peritoneal cavity. The
rats received a continuous intragastric infusion of one of three diets: Gln-depleted (Gln 0),
Gln-enriched with the Gln in free amino acid form (Gln F), or Gln-enriched with the Gln in
oligopeptide form (Gln P). The three formulas were isocaloric and isonitrogenous. The
pumps delivered a continuous infusion of Escherichia coli, starting at 48 hours after
implantation, for 24 hours. Then, the animals were killed. RESULTS: Bacterial numbers in
peritoneal lavaged fluid (PLF) and the liver were significantly lower in the Gln P and Gln F
groups than in the Gln 0 group. The bacterial number in PLF correlated with that in the liver.
Neither the number nor the population of peritoneal exudative cells differed among groups.
Plasma levels of proline, alanine and citrulline were significantly higher in the Gln P and
Gln F groups than in the Gln 0 group. Both Gln supplemented groups showed significantly
greater villous height, crypt depth, and numbers of mitoses per crypt in the small intestine
than the Gln 0 group. CONCLUSIONS: Supplemental Gln enhances peritoneal and hepatic
bacterial clearance, regardless of Gln form. Gln-enriched may be more beneficial than
Gln-depleted enteral diets in peritonitis.

Title

Intravenous glutamine fails to improve gut morphology after radiation injury.
Author

Scott TE; Moellman JR
Source
JPEN J Parenter Enteral Nutr, 1992 Sep, 16:5, 440-4
Abstract

Male Sprague-Dawley rats housed in individual metabolic cages received total parenteral
nutrients via chronic indwelling internal jugular catheters to determine whether
supplementing parenteral nutrition with glutamine would accelerate recovery of small-bowel
morphology after abdominal radiation. After recovering from catheter insertion for 3 days
they received either 1000 cGy gamma radiation to the abdomen only or no radiation and
immediately thereafter received isonitrogenous and isocaloric intravenous solutions
containing either 0% or 2% glutamine at 1.58 mL/h for the next 5 days. Intestinal segments
were then assayed for whole-bowel deoxyribose nucleic acid content and villus height.
Irradiation caused a 40% decrement in these parameters, which were not restored by
glutamine supplementation. Therefore, intravenous glutamine supplementation failed to
accelerate recovery of small-bowel morphology in this model of combined surgical and
radiation injury.

Title

The role of glutamine in maintaining a healthy gut and supporting the metabolic response to
injury and infection.
Author

Souba WW; Klimberg VS; Plumley DA; Salloum RM; Flynn TC; Bland KI; Copeland
EM 3d
Source
J Surg Res, 1990 Apr, 48:4, 383-91
Abstract

In the critically ill surgical patient a variety of therapeutic maneuvers is required to maintain
a "healthy gut." Provision of adequate amounts of glutamine to the gastrointestinal mucosa
appears to be just one of these maneuvers. Other methods utilized to protect the gut from
becoming a wound include: (a) minimizing additional systemic insults (such as
hypotension, sepsis, multiple operative procedures); (b) aggressive pulmonary care; (c) the
judicious use of antibiotics; and (d) aggressive enteral or parenteral feedings. The concept
that the gut is an organ of quiescence following surgical stress merits reconsideration. The
intestinal tract plays a central role in interorgan glutamine metabolism and is a key regulator
of nitrogen handling following surgical stress. Critically ill patients are susceptible to
developing gut-origin sepsis, the incidence of which will be diminished by instituting
measures and providing treatments which support intestinal structure, function, and
metabolism. Provision of glutamine-enriched diets to such patients may be one of these
therapies.

Title

Glutamine.
Author

Hall JC; Heel K; McCauley R
Source
Br J Surg, 1996 Mar, 83:3, 305-12
Abstract

Glutamine is the most abundant free amino acid in the circulation. It is a primary fuel for
rapidly dividing cells and plays a key role in the transport of nitrogen between organs.
Although glutamine is absent from conventional regimens aimed at nutritional support,
glutamine deficiency can occur during periods of metabolic stress; this has led to the
reclassification of glutamine as a conditionally essential amino acid. Experiments with
various animal models have demonstrated that the provision of glutamine can result in better
nitrogen homoeostasis, with conservation of skeletal muscle. There is also considerable
evidence that glutamine can enhance the barrier function of the gut. This review concludes
by discussing the clinical evidence that supports the inclusion of stable forms of glutamine
in solutions of nutrients.

Title

Intestinal fuels: glutamine, short-chain fatty acids, and dietary fiber [see comments]
Author

Evans MA; Shronts EP
Source
J Am Diet Assoc, 1992 Oct, 92:10, 1239-46, 1249
Abstract

In recent years, considerable research has focused on the physiologic effects and clinical
uses of three dietary constituents thought to be trophic to the intestinal tract in human beings:
glutamine, short-chain fatty acids (SCFAs), and dietary fiber. Glutamine is an important
nitrogen-carrying amino acid that may be "conditionally essential" in certain disease states to
support the gut barrier and immune function and overall protein use. Colonic irrigations
with SCFA preparations have demonstrated enhanced healing of bowel tissue in animals
and human beings. Dietary fiber supports bacterial SCFA production, normal stool output,
and the gut barrier and immune function. However, optimal fiber doses for various medical
conditions are not known, and the risk for gastrointestinal (GI) obstruction, diarrhea, gas,
and bloating necessitates careful selection of patients and daily monitoring of fiber tolerance.
A review of the current literature indicates that widespread use of glutamine and SCFA
additives parenterally and enterally awaits further evidence of safety and efficacy in human
beings, establishment of appropriate doses, and advances in formulation technology.
Administration of dietary fiber to enhance bowel motility should be considered in long-term
tube-fed patients with intact GI function and sufficient fluid tolerance to permit hydration of
fiber. Industrywide agreement on fiber analysis methods and labeling standards (eg, fiber
fermentability vs solubility) would facilitate selection of enteral products. To streamline
studies and optimize research efforts in future clinical trials, standard criteria for evaluating
GI function, diarrheagenic factors, and intestinal outcome variables should be established.

Title

The effect of glutamine-enriched TPN on gut immune cellularity.
Author

Alverdy JA; Aoys E; Weiss Carrington P; Burke DA
Source
J Surg Res, 1992 Jan, 52:1, 34-8
Abstract

Prolonged parenteral feeding with standard nutrient solutions results in significant alteration
in the structural, hormonal, and immunological composition of the intestinal tract. The
purpose of the following study was to evaluate the effect of glutamine-supplemented
parenteral nutrition on the immune cellularity of the gut. Twenty-one Fischer rats were
randomized to three groups of seven animals each. Group I was fed rat chow and water ad
lib, Group II was fed a standard solution of total parenteral nutrition (TPN) (D25/4.25%
amino acids) via a central venous catheter, and Group III was fed the standard solution of
TPN with 2% glutamine which was isonitrogenous and isocaloric to Group II. Animals
were fed their respective diets for 1 week and bile was collected and assayed for secretory
IgA (s-IgA) and IgM. The terminal ileum was stained and assayed for IgA+, IgM+, IgG+,
CD4+, and CD8+ plasma cells and lymphocytes. Results indicate that the feeding of a
standard parenteral diet results in a significant decrease in biliary s-IgA and IgA+ plasma
cells in the gut lamina propria compared to chow-fed animals (S-IgA: chow, 858 +/- 23
micrograms/ml; TPN, 494 +/- 41 micrograms/ml; IgA cells: chow, 35.7 +/- 1.8; TPN, 8.6
+/- 0.9 cells/hpf). In addition a marked depletion of CD4+ and CD8+ lymphocytes was
observed with standard solutions of parenteral nutrition compared to chow (CD4+: chow,
36.8 +/- 6.6; TPN, 14.9 +/- 6.0; CD8+: chow, 18.8 +/- 5.6; TPN, 5.7 +/- 2.7 cells/hpf). The
addition of glutamine to the standard TPN solution maintained both B and T cell populations
at levels similar to chow-fed animals.(Abstract TRUNCATED AT 250 WORDS)

Title

Glutamine and cancer.
Author

Souba WW
Source
Ann Surg, 1993 Dec, 218:6, 715-28
Abstract

OBJECTIVE: This overview on glutamine and cancer discusses the importance of
glutamine for tumor growth, summarizes the alterations in interorgan glutamine metabolism
that develop in the tumor-bearing host, and reviews the potential benefits of glutamine
nutrition in the patient with cancer. SUMMARY BACKGROUND DATA: Glutamine is
the most abundant amino acid in the blood and tissues. It is essential for tumor growth and
marked changes in organ glutamine metabolism are characteristic of the host with cancer.
Because host glutamine depletion has adverse effects, it is important to study the regulation
of glutamine metabolism in cancer and to evaluate the impact of glutamine nutrition in the
tumor-bearing state. METHODS: Data from a variety of investigations on glutamine
metabolism and nutrition related to the host with cancer were compiled and summarized.
RESULTS: Numerous studies on glutamine metabolism in cancer indicate that many
tumors are avid glutamine consumers in vivo and in vitro. As a consequence of progressive
tumor growth, host glutamine depletion develops and becomes a hallmark. This glutamine
depletion occurs in part because the tumor behaves as a "glutamine trap" but also because of
cytokine-mediated alterations in glutamine metabolism in host tissues. Animal and human
studies that have investigated the use of glutamine-supplemented nutrition in the host with
cancer suggest that pharmacologic doses of dietary glutamine may be beneficial.
CONCLUSIONS: Understanding the control of glutamine metabolism in the tumor-bearing
host not only improves the knowledge of metabolic regulation in the patient with cancer but
also will lead to improved nutritional support regimens targeted to benefit the host.

Title

Role of glutamine in bacterial transcytosis and epithelial cell injury.
Author

Panigrahi P; Gewolb IH; Bamford P; Horvath K
Source
JPEN J Parenter Enteral Nutr, 1997 Mar, 21:2, 75-80
Abstract

BACKGROUND: L-Glutamine is the principal energy source for small intestinal
enterocytes. Diminution of intestinal function, mucosal atrophy, and increased bacterial
translocation have been noted during total parenteral nutrition (TPN). In a rat model of
glutamine starvation, we previously showed that luminal glutamine is essential for optimal
intestinal function. In this study, we examined the effect of apical vs basolateral glutamine
on bacterial translocation in a Caco-2 cell culture system and bacteria-induced tissue injury
in a weanling rabbit ileal loop model. METHODS: Caco-2 cells were grown in a transwell
system. After confluence, apical and basolateral chambers received defined media, and
glutamine deprivation was carried out over a 4- to 48-hour period. Escherichia coli
transcytosis and structure/function studies were then performed. In a second series of
experiments, the effect of intraluminal glutamine supplementation was evaluated in an E.
coli-induced tissue injury model in weanling rabbit ileal loops. RESULTS: Expression of
disaccharidases, glucoamylase, and Na+/K(+)-adenosine 5'-triphosphatase (ATPase) were
significantly reduced when cells were deprived of glutamine from the apical side, and there
was increased bacterial translocation across the monolayer. Transepithelial epithelial
resistance (TEER) across the monolayer was also reduced in the glutamine-free cultures.
Glutamine replenishment over 24 to 48 hours restored the original functions. Basolateral
deprivation had a smaller effect on the Caco-2 cells. Typical necrotic mucosal injury caused
by E. coli in the ileal loops was blocked by co-infiltration of the loops with glutamine.
CONCLUSIONS: This study demonstrates for the first time that the supply of glutamine
from the apical side is of critical importance for maintaining optimal structure and function
of the enterocytes. The effects are not acute or energy related. These observations have
important clinical implications in the management of patients under critical care, including
premature infants and patients receiving TPN, for whom lack of glutamine from the luminal
side could produce mucosal dysfunction, resulting ultimately in severe atrophic/necrotic
complications.

 

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