This study evaluated the protective effects of glutamine on intestinal permeability and bacterial translocation in rats receiving total parenteral nutrition (TPN) with endotoxemia. Thirty-four rats were divided into four groups: a control group, a TPN group, a trauma and endotoxemia group, and a trauma plus endotoxemia group that received glutamine in TPN. Glutamine supplementation was found to decrease intestinal permeability and bacterial translocation compared to the trauma and endotoxemia group as measured by urinary lactulose and mannitol levels and mesenteric lymph node cultures. This suggests glutamine protects intestinal barrier function in rats with endotoxemia receiving TPN.

1. Glutamine
S.Suhandono
created by SS 1

2. Glutamine
 Hydrophilic
 Nonessential amino
acid
 “Conditionally
Essential" amino acid
during high stress
such as burns, injury,
or inflammatory bowel
conditions
created by SS 2

3. Glutamine
 The most abundant amino acid in the human
body
 Precursor for nucleotide synthesis
 Promotes protein synthesis and muscle growth
 Primary source of energy for cells in the lining of
the GI tract
 Promote GI tract healing and nutritional
supplementation with GI disorders
 ↓bacterial adhesion to enterocytes and bacterial
translocation
created by SS 3

4. created by SS 4

5. created by SS 5

6. Nutritional management of
severe sepsis and septic shock
 Early nutritional support improves wound healing
and ↓the susceptibility of critically ill patients to
infection
 Early enteral nutrition may offer more benefit in
preventing sepsis than parenteral nutrition
 Immune-enhancing nutrients and antioxidants,
including arginine and glutamine
Evidence-based analysis of nutrition support in sepsis. In:
Clinical Trials for the treatment of sepsis, Sibbald, WJ,
Vincent, JL (Eds), Springer Verlag, Berlin, 1995, p. 223.
created by SS 6

7. Nutritional management of
severe sepsis and septic shock
 Such enteral formulas may favorably
affect the resistance of the gut to bacterial
translocation or exert direct effects on the
behavior of intraluminal bacteria
Oral glutamine decreases bacterial translocation and improves survival
in experimental gut-origin sepsis. JPEN J Parenter Enteral Nutr
1995; 19:69
created by SS 7

8. Glutamine in the critically ill
In a meta-analysis of 14 randomized, controlled
trials that evaluated glutamine-enriched nutrition
(both enteral and parenteral) in a population of
post-operative and critically ill patients,
→There was no effect on mortality, infectious
complications, or length of hospital stay
Glutamine supplementation in serious illness: a systematic review of
the evidence. Crit Care Med 2002; 30:2022.
 This results may be due to the combination of
enteral and parenteral nutrition into a single
meta-analysis
created by SS 8

9. Glutamine in the critically ill
In a meta-analysis of seven trials
comparing enteral nutrition with and
without glutamine
→There was no difference in mortality or
infectious complications
Composition of EN, immune enhancing diets, glutamine.
www.criticalcarenutrition.com. (Accessed August 29, 2006).
created by SS 9

10. Glutamine in the critically ill
A meta-analysis of four randomized
controlled trials (397 patients)
→Glutamine-enriched parenteral nutrition
decreased mortality
Canadian clinical practice guidelines for nutrition support in
mechanically ventilated, critically ill adult patients. JPEN J Parenter
Enteral Nutr 2003; 27:355 .
created by SS 10

11. Glutamine Modulates Phenotypes and
Stimulates Proliferation in Human Colon
Cancer Cell Lines
Cancer Research 54, 5974-5980, 1994
 Human colon carcinoma cell lines( Caco-2 and
SW620), in vitro study
 Glutamine
 Stimulates proliferation
 ↓Brush border enzyme expression→suggesting a loss
of cellular differentiation
 ↓ Both adhesion and integrin surface expression→
Higher propensity of these cancer cells for invasion
and metastasis
 Further study: from in vitro to in vivo
created by SS 11

12. Glutamine Supplementation in Cancer
Patients
Nutrition 2001;17: 766–768
 The glutamine derived from skeletal muscle is trapped
by the tumor
The role of glutamine in the oxidative metabolism of
malignant cells. Cancer Res 1972;32:326
→an important concern of glutamine supplementation in
cancer patients is its use by the tumor, with potential
enhancement of tumor growth
 Glutamine enriched diet support muscle glutamine
metabolism without stimulating tumor growth.
J Surg Res1989;48:319
→ supplemented glutamine can be used in non-tumor
tissues such as muscle, lymphocytes, and the gut
mucosa
created by SS 12

13. Glutamine Supplementation in
Cancer Patients
Nutrition 2001;17: 766–768
 Glutamine depletion in host tissues occurs in tumor-
bearing rats
→to meet energy requirements during catabolic states
such as trauma, sepsis, and tumor burden
 Tumor protein synthesis, DNA synthesis, and tumor
weight were not stimulated by glutamine
supplementation.
 Neither glutamine nor glutathione levels in tumors were
elevated by glutamine supplementation
→Use of glutamine by the tumors was already at a
maximum in tumor-bearing rats and that any
supplemented glutamine was used by host tissues.
created by SS 13

14. Glutamine Supplementation in
Cancer Patients
Nutrition 2001;17: 766–768
 Glutamine supplementation can attenuate
loss of protein in the muscle in tumor-
bearing animals and protect immune and
gut-barrier function during
radiochemotherapy in patients with
advanced cancer.
created by SS 14

15. WHAT ARE CD4 CELLS?
 CD4 (cluster of differentiation 4) is a glycoprotein expressed on the
surface of T helper cells, monocytes, macrophages, and dendritic
cells. It was discovered in the late 1970s and was originally known
as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted
with it) before being named CD4 in 1984.[2] In humans, the CD4
protein is encoded by the CD4 gene
 CD4 cells are a type of lymphocyte (white blood cell). They are an
important part of the immune system. CD4 cells are sometimes
called T-cells. There are two main types of CD4 cells. T-4 cells, also
called CD4+, are "helper" cells. They lead the attack against
infections. T-8 cells (CD8+) are "suppressor" cells that end the
immune response. CD8 cells can also be "killer" cells that kill cancer
cells and cells infected with a virus.
 Researchers can tell these cells apart by specific proteins on the
cell surface. A T-4 cell is a T-cell with CD4 molecules on its surface.
This type of T-cell is also called "CD4 positive," or CD4.
created by SS 15

16. What are CD4 and CD8 tcells
 CD4 are T-helper (T-h) cells and CD8 cells are T-c cells. CD4 and
CD8 (CD means "cluster of differentiation") are surface proteins
found on their respected cells.
 The main difference between them are that T-h cells are involved in
antigen presentation to B cells, and T-c cells are involved in indirect
phagocytosis (when they become cytotoxic-T cells, whenever they
are induced to doing so).
created by SS 16

17. Effect of glutamine on nutrition in patients with chronic
obstructive pulmonary disease and antioxidant therapy
immunomodulatory role
Yan Li Chun-Xia Liu Chao Ping WEI Xin Zia
[Abstract] Objective To study glutamine in chronic obstructive pulmonary disease (COPD) patients with acute
exacerbation of nutritional status, immune function and antioxidant effects. Methods 115 patients with acute
exacerbation of COPD were randomly assigned to conventional treatment group and the Valley ammonia amide group
(Gln) groups. conventional treatment group received conventional nutrition therapy, Gln group, oral glutamine 10 g, 3
times a day, continuous treatment with 10 d. Results Gln group triceps skinfold thickness , long upper arm muscle
circumference and plasma total protein and other nutritional parameters improved significantly compared with the
conventional group. Gln group IgG, IgA, CD3, CD4, CD4/CD8 and glutathione (GSH) was significantly higher (P
<0.05). Conclusion Glutamine can improve patients with acute exacerbation of COPD nutrition and immune function,
but also can improve the antioxidant capacity.
[Keywords:] Chronic obstructive pulmonary disease; glutamine; nutrition; immunization; antioxidant
Chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality, serious harm to health of the
elderly. COPD with acute exacerbation of elderly patients with severe immune dysfunction and malnutrition (1), so to
improve their immune function and nutrition treatment to improve the prognosis is extremely important. In this study,
application of glutamine (Gln) of COPD patients
created by SS 17

18. Protective effect of glutamine in critical patients
with acute liver injury
Hai-bin Ni, Zheng Zhang, Hai-dong Qin
Author Affiliation: Department of Emergency, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China
© 2011 World Journal of Emergency Medicine
BACKGROUND: Glutamine (Gln) supplementation is known to decrease oxidative stress and inflammatory response,
enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was
undertaken to evaluate the relationship between the effect of early parenteral glutamine (Gln) supplement on acute liver
injury (ALI) and heat shock protein 70 (HSP-70) expression in critical patients.
METHODS: Forty-four patients who had been admitted to the emergency intensive care unit (EICU) of Nanjing First
Hospital Affiliated to Nanjing Medical University were randomly divided into a control group (n=22) and a Gln group (n=22).
The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gln 0.4 g/kg per day was
given for 7 days in the Gln group. Serum HSP-70 and Gln were measured at admission and at 7 days after admission.
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL), serum levels of HSP-
70 and Gln, mechanical ventilation (MV) time, ICU stay, peripheral blood of plasma TNF-α, IL- 6, CD3, CD4 and CD4/CD8
levels were also measured in the two groups.
RESULTS: In the Gln group, the levels of serum HSP-70 and Gln were significantly higher after Gln treatment than those
before the treatment (P<0.01). HSP-70 level was positively correlated with the Gln level in the Gln group after
administration of parenteral Gln (P<0.01). The levels of serum ALT, AST, TBiL and TNF-α, IL-6 were lower in the Gln
group than in the non-Gln group (P<0.01). MV time and ICU stay were significantly different between the two groups
(P<0.05). The levels of CD3, CD4 and CD4/ CD8 were significantly higher in the Gln group than in the control group after
treatment (P<0.05).
CONCLUSION: Parenteral Gln significantly increases the level of serum HSP70 in critically ill patients. The enhanced
expression of HSP70 is correlated with improved outcomes of Gln-treated patients with acute liver injury.
(World J Emerg Med 2011; 2: 210-215)
created by SS 18

19. The effect of protein metabolism and immunologic function
of glutamine after operation in elder gastrointestinal tumor
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2011 Mar;27(3):322-3.
Abstract
AIM:
To explore the effect of protein metabolism and immunologic function of glutamine after operation in elder
gastrointestinal tumor.
METHODS:
Form march 2007 to 2010, 87 cases of elder gastrointestinal tumor were given parenteral nutrition and glutamine 0.6 g/
( Kg x d).The period of treatment were 8 days. IgA, IgG, IgM were CD4, measured by single immunodiffusion, CD3(+),
CD4(+), CD8(+), CD4(+) /CD8(+) were measured by immunohistochemical method, and the index(Alb, PAB, TF,
nitrogen equilibrium) were monitored the proteid catabolism distribution.
RESULTS:
After the treatment, CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), IgG, IgA, IgM were evidently declined( P <0.05). Alb,
PAB, TF were evidently declined in 4 days postoperatively (P < 0.05), the restore were more obvious in 8 days
postoperatively (P < 0. 05). Nitrogen equilibrium was worse in the early postoperative and the restore were more
obvious in 8 days postoperatively (P < 0.05).
CONCLUSION:
Glutamine can improve patient's nutrition, enhance their immunologic function.
PMID: 21638931 [PubMed - indexed for MEDLINE]
created by SS 19

20. L-alanyl-L-glutamine-supplemented parenteral
nutrition decreases infectious morbidity rate in
patients with severe acute pancreatitis.
Fuentes-Orozco C, Cervantes-Guevara G, Muciño-Hernández I ; JPEN J Parenter Enteral Nutr. 2008 Jul-
Aug;32(4):403-11.
Abstract
BACKGROUND: The effect of parenteral GLN on recovery from severe acute pancreatitis has not been thoroughly
investigated. The aims of this study were to determine whether parenteral GLN improves nutrition status and immune
function, and to determine its ability to reduce morbidity and mortality in patients with this condition.
METHODS: In a randomized clinical trial, 44 patients with severe acute pancreatitis were randomly assigned to receive
either standard PN (n = 22) or l-alanyl-l-glutamine-supplemented PN (n = 22) after hospital admission. Nitrogen
balance, counts of leukocytes, total lymphocytes, and CD4 and CD8 subpopulations, and serum levels of
immunoglobulin A, total protein, albumin, C-reactive protein, and serum interleukin (IL)-6 and IL-10 were measured on
days 0, 5, and 10. Hospital stay, infectious morbidity, and mortality were also evaluated.
RESULTS: Demographics, laboratory characteristics, and pancreatitis etiology and severity at entry to the study were
similar between groups. The study group exhibited significant increases in serum IL-10 levels, total lymphocyte and
lymphocyte subpopulation counts, and albumin serum levels. Nitrogen balance also improved to positive levels in the
study group and remained negative in the control group. Infectious morbidity was more frequent in the control group
than in the study group. The duration of hospital stay was similar between groups, as was mortality.
CONCLUSION: The results suggest that treatment of patients with GLN-supplemented PN may decrease infectious
morbidity rate compared with those who treated with nonenriched PN.
created by SS 20

21. Effects of glutamine on intestinal permeability and
bacterial translocation in TPN-rats with endotoxemia
World J Gastroenterol 2003;9(6):1327-1332
Abstract
AIM: To evaluate the protective effect and mechanism of glutamine on the intestinal barrier function in total parenteral nutrition
(TPN) rats with trauma or endotoxemia.
METHODS: To perform prospective, randomized and controlled animal experimentation of rats with surgical
trauma, TPN and endotoxemia, thirty-four male, adult Sprague Dawley rats were divided into four groups: control
group (n=8), TPN group (n=9), trauma and endotoxemia group (LPS, n=8) and trauma plus endotoxemia supplemented with
glutamine in TPN solution group (Gln. group, n=9). All groups except the control group were given TPN solutions in 7-day
experimental period. For Gln group, 1 000 mg/kg/d of glutamine was added to TPN solution during day 1-6. On the 7th day all
the animals were gavaged with lactulose (66 mg) and mannitol (50 mg) in 2 ml of normal saline. Then 24 h urine with
preservative was collected and kept at -20 . On day 8, under intraperitoneal anesthesia using 100 mg/kg ketamin, the intestine,
liver, mesenteric lymph nodes and blood were
taken for examination.
RESULTS: The body weight of LPS group decreased most among the four groups. The structure of small intestinal
mucosa in TPN group, LPS group and Gln group showed impairments of different degrees, and the damage of small
intestinal mucosa in Gln group was remarkably alleviated. The concentrations of interleukins in small intestine mucosa
were lower (for IL-4 and IL-6) or the lowest (IL-10) in Gln group. The IgA level in the blood plasma and the mucosa
of Gln group was the highest among all of the groups. The urine lactulose/mannitol test showed that the intestinal
permeability in LPS group was lower than that in TPN group (P<0.001), but there was no difference between LPS group
and Gln group. The rate of bacterial translocation in Gln group was lower than that in LPS group (P<0.02).
CONCLUSION: Prophylactic treatment with glutamine could minimize the increments of intestinal permeability
and bacterial translocation caused by trauma and endotoxemia in rats treated with TPN.
created by SS 21

22. Effect of parenteral glutamine on restoration of lymphocyte
subpopulations after high-dose chemotherapy and autologous
hematopoietic cell transplantation: data from a double-blind
randomized study
Pytlík R, Gregora E, Benes P, Kozák T. Epidemiol Mikrobiol Imunol. 2002 Nov;51(4):152-5
Abstract
Within the framework of a randomized double blind study focused on the effect of glutamine on the
clinical course of autologous transplantation of peripheral cells the authors assessed lymphocyte sub-
populations (CD3, CD4, CD8, CD19 and CD57+ cells) before transplantation and 14, 28 and 42 days
after transplantation. A total of 36 patients were investigated (18 glutamine, 18 placebo). In the whole
group of patients the authors found restoration of CD4 and CD19 cells to pre transplantation values
one day +42 after transplantation, in CD8 and CD57 cells a statistically significant increase as
compared with the pre-transplantation state occurred. In the glutamine group they observed on day
+28 a more rapid restoration of CD8 and a marginally better restoration of CD19 positive cells, while
patients who were given placebo restored CD57+ cells more rapidly. All these differences were
balanced on day +42, only CD19+ cells were at that time marginally higher in the placebo group. With
the exception of CD19+ lymphocytes the authors observed weak correlations between the number of
lymphocytes on day +42 after transplantation and the number of transplanted CD34+ cells. It may
thus be stated that the drop of lymphocyte sub-populations has a short-term character, the restoration
correlates among others with the administered amount of haematopoietic cells. Significant importance
of glutamine for the restoration of the lymphocyte sub-population was however not proved
created by SS 22

23. Thank You!
created by SS 23