and HBeAg(-) patients - World Journal of Gastroenterology

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amino acid, glutamine. Glutamine has attracted close attention as an amino acid nutrient and as an immunopotentiating factor for intestinal cells [14-16] . However, no case of intestinal hemorrhage induced by glutamine deficiency has been reported to date. Although glutamine is a nonessential amino acid and can be produced in the living body, neonatal mice are actively growing and are very dependent on external alimentation due to a heavier consumption of nutrients, including glutamine, compared to adults [17] . It seems likely that the consumption of glutamine by these neonatal mice might exceed the amount of glutamine pooled and formed in the living body, leading to the emergent status of glutamine deficiency. In terms of molecular/biological effects of glutamine, there are outstanding several issues that remain to be clarified. One of our interests is to explore the possible involvement of certain signaling pathways. It has recently been unveiled that amino acids are involved in the control of the mTOR signaling pathway [18] . We have also demonstrated previously that leucine activates the mTOR signaling pathway in a hepatocellular carcinoma cell line [19] . It has also been shown that leucine and arginine activate the mTOR signaling pathway in a small bowel epithelial cell line derived from rats [20] . We also found that glutamine regulates the activation of this pathway in the same cell line [21] . Therefore, future studies should focus on the mechanism for the induction of colonic hemorrhage and how glutamine is involved in the intracellular signaling pathway, such as in mTOR [22-24] . In conclusion, we found that feeding neonatal mice with GDM induced a high incidence of colonic hemorrhage within a week, and that this was due to an induction of epithelial cell death. Further investigation is necessary to explore the biological mechanism. ACKNOWLEDGMENTS We are grateful to Ms. Kazuko Tunashima, Ms. Tae Yamanishi, and Mr. Toru Tanida for technical assistance, Dr. Yuko Ohno (Department of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan) for supervising the statistical analysis, and Drs. Minoru Haisa (Okayama Citizens’ Hospital, Okayama, Japan), Keiichiro Nishida, Kazuhiro Noma and Shunsuke Tanabe (Okayama University) for useful discussions. COMMENTS Background Glutamine, the most abundant amino acid in the human body, is conditionally essential, especially for susceptible individuals who are in high stress conditions. A lack of glutamine correlates with increased mortality. Research frontiers The small intestine accounts for the largest uptake of glutamine of any organ, absorbing this amino acid from the lumen of the gut, as well as from the bloodstream. Past studies involved the evaluation of immunological effects of amino acids by the administration of a diet rich or deficient in each amino acid (glutamine, arginine, etc.) by means of total parenteral nutrition or stomach tubing. However, no such study in newborn mice has yet been reported. The lack of such a study in newborn mice is attributable to the difficulty in developing a method of alimentation or preparing a diet for neonatal mice. WJG|www.wjgnet.com Motoki T et al . Glutamine depletion induces neonatal melena Innovations and breakthroughs The authors developed three kinds of artificial milk with different amounts of glutamine. Using these amino acid milks and a recently improved nipple-bottle feeding system, they successfully fed the newborn mice with the new amino acid milk and observed colonic hemorrhage in mice fed without glutamine. It was remarkable that colonic hemorrhage could be induced simply by removing one amino acid, glutamine. In addition, glutamine deprivation can cause instability of intestinal epithelial alignment by increased apoptosis. Applications No exact intracellular mechanism has been identified for the destruction of the nuclear membrane and microvilli or the disappearance of glycocalyx, which were induced by glutamine depletion. Thus, we must explore the mechanism of the induction of colonic hemorrhage and investigate glutamine’s involvement in the intracellular signaling pathway, to better understand the intrinsic functions of glutamine and other amino acids. Peer review The authors have described that glutamine depletion induces neonatal mice melena and apoptosis of intestinal epithelium in vivo and in vitro. The authors obtained good data allowing the conclusion that glutamine depletion induces neonatal mice melena and apoptosis of intestinal epithelium, using appropriate methods. An animal model was established for glutamine deprivation-induced destruction of the intestinal epithelium. It would also be meaningful to study the effects of glutamine-deprivation on human intestinal function. REFERENCES 1 D'Souza R, Powell-Tuck J. Glutamine supplements in the critically ill. J R Soc Med 2004; 97: 425-427 2 Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002; 30: 2022-2029 3 Scheltinga MR, Young LS, Benfell K, Bye RL, Ziegler TR, Santos AA, Antin JH, Schloerb PR, Wilmore DW. Glutamineenriched intravenous feedings attenuate extracellular fluid expansion after a standard stress. Ann Surg 1991; 214: 385-393; discussion 393-395 4 Thompson SW, McClure BG, Tubman TR. A randomized, controlled trial of parenteral glutamine in ill, very low birthweight neonates. J Pediatr Gastroenterol Nutr 2003; 37: 550-553 5 Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997; 13: 295-302 6 Danbolt NC. Glutamate uptake. Prog Neurobiol 2001; 65: 1-105 7 Becker RM, Wu G, Galanko JA, Chen W, Maynor AR, Bose CL, Rhoads JM. Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 2000; 137: 785-793 8 Biolo G, Zorat F, Antonione R, Ciocchi B. Muscle glutamine depletion in the intensive care unit. Int J Biochem Cell Biol 2005; 37: 2169-2179 9 Avenell A. Hot topics in parenteral nutrition. Current evidence and ongoing trials on the use of glutamine in critically-ill patients and patients undergoing surgery. Proc Nutr Soc 2009; 68: 261-268 10 Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, Mendenhall WM, Bova FJ, Khan SR, Hackett RL. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990; 66: 62-68 11 Manhart N, Vierlinger K, Spittler A, Bergmeister H, Sautner T, Roth E. Oral feeding with glutamine prevents lymphocyte and glutathione depletion of Peyer's patches in endotoxemic mice. Ann Surg 2001; 234: 92-97 12 Yajima M, Kanno T, Yajima T. A chemically derived milk substitute that is compatible with mouse milk for artificial rearing of mouse pups. Exp Anim 2006; 55: 391-397 13 Hoshiba J. Method for hand-feeding mouse pups with nursing bottles. Contemp Top Lab Anim Sci 2004; 43: 50-53 14 Yagi M, Sakamoto K, Hasebe K, Ito H, Onishi I, Tani T, 725 February 14, 2011|Volume 17|Issue 6|
Motoki T et al . Glutamine depletion induces neonatal melena Hashimoto T, Shimizu K, Miwa K. Effect of a glutamineenriched diet on small bowel allograft during immunosuppressive therapy. Nutrition 1997; 13: 778-782 15 Marion R, Coëffier MM, Gargala G, Ducrotté P, Déchelotte PP. Glutamine and CXC chemokines IL-8, Mig, IP-10 and I-TAC in human intestinal epithelial cells. Clin Nutr 2004; 23: 579-585 16 Dupont B, Dupont C, Justum AM, Piquet MA, Reimund JM. Enteral nutrition in adult Crohn's disease: present status and perspectives. Mol Nutr Food Res 2008; 52: 875-884 17 Pierro A, Eaton S. Metabolism and nutrition in the surgical neonate. Semin Pediatr Surg 2008; 17: 276-284 18 Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 1998; 273: 14484-14494 19 Shigemitsu K, Tsujishita Y, Miyake H, Hidayat S, Tanaka N, Hara K, Yonezawa K. Structural requirement of leucine for activation of p70 S6 kinase. FEBS Lett 1999; 447: 303-306 20 Ban H, Shigemitsu K, Yamatsuji T, Haisa M, Nakajo T, Takaoka M, Nobuhisa T, Gunduz M, Tanaka N, Naomoto Y. WJG|www.wjgnet.com Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cells. Int J Mol Med 2004; 13: 537-543 21 Nakajo T, Yamatsuji T, Ban H, Shigemitsu K, Haisa M, Motoki T, Noma K, Nobuhisa T, Matsuoka J, Gunduz M, Yonezawa K, Tanaka N, Naomoto Y. Glutamine is a key regulator for amino acid-controlled cell growth through the mTOR signaling pathway in rat intestinal epithelial cells. Biochem Biophys Res Commun 2005; 326: 174-180 22 Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009; 136: 521-534 23 Sakiyama T, Musch MW, Ropeleski MJ, Tsubouchi H, Chang EB. Glutamine increases autophagy under Basal and stressed conditions in intestinal epithelial cells. Gastroenterology 2009; 136: 924-932 24 Fumarola C, La Monica S, Guidotti GG. Amino acid signaling through the mammalian target of rapamycin (mTOR) pathway: Role of glutamine and of cell shrinkage. J Cell Physiol 2005; 204: 155-165 S- Editor Sun H L- Editor Stewart GJ E- Editor Lin YP 726 February 14, 2011|Volume 17|Issue 6|
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World Journal of Gastroenterology W
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Robert JL Fraser, Daw Park Jacob Ge
Page 5 and 6: Italy Donato F Altomare, Bari Piero
Page 7 and 8: Fernando Azpiroz, Barcelona Ramon B
Page 9 and 10: S Contents EDITORIAL REVIEW ORIGINA
Page 11 and 12: Contents ACKNOWLEDGMENTS APPENDIX A
Page 13 and 14: Jahn KA et al . Colon cancer and li
Page 23 and 24: Săftoiu A. Imaging techniques in E
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Page 42 and 43: Table 2 Comparison of hepatitis B e
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Page 61 and 62: Abundance/× 10 6 Abundance/× 10 6
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Page 72 and 73: obese and exhibited higher insulin
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Page 77 and 78: Roberts SE et al . Perinatal factor
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Goenka MK et al . Capsule endoscopy
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Tatsuki M et al . Hypermagnesemia a
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Chang CC et al . Parity and gastric
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Chang CC et al . Parity and gastric
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Zhang XQ et al . EEA model of guine
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Table 3 Measurement of common bile
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Zhang XQ et al . EEA model of guine
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Zhao R et al . Gene expression anal
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Zhao R et al . Gene expression anal
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Qiu HB et al . HBV infection and li
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Qiu HB et al . HBV infection and li
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Shen H et al . K-ras and BRAF mutat
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