Glutamine

Glutamine

S.Suhandono

created by SS 1

Glutamine

Hydrophilic Nonessential amino

acid “Conditionally

Essential" amino acid during high stress such as burns, injury, or inflammatory bowel conditions

created by SS 2

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

created by SS 4

created by SS 5

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 glutamineEvidence-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

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

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

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

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

Glutamine Modulates Phenotypes and Stimulates Proliferation in Human Colon Cancer Cell LinesCancer 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 vivocreated by SS 11

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

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

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

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

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

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

Protective effect of glutamine in critical patients with acute liver injuryHai-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

The effect of protein metabolism and immunologic function of glutamine after operation in elder gastrointestinal tumorXi 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

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

Effects of glutamine on intestinal permeability and bacterial translocation in TPN-rats with endotoxemiaWorld 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

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

Thank You!

created by SS 23