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Nista EC, Parello S, Brigida M, Amadei G, Saviano A, De Lucia SS, Petruzziello C, Migneco A, Ojetti V. Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review. Int J Mol Sci 2025; 26:3433. [PMID: 40244415 PMCID: PMC11989318 DOI: 10.3390/ijms26073433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 04/18/2025] Open
Abstract
Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.
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Affiliation(s)
- Enrico Celestino Nista
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Simone Parello
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Mattia Brigida
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy;
| | - Giulio Amadei
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Angela Saviano
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Sara Sofia De Lucia
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | | | - Alessio Migneco
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Veronica Ojetti
- Ospedale San Carlo di Nancy, GVM Research, 00165 Rome, Italy
- Department of Internal Medicine, UniCamillus International Medical University of Rome, 00131 Rome, Italy
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Tang G, Pi F, Qiu YH, Wei ZQ. Postoperative parenteral glutamine supplementation improves the short-term outcomes in patients undergoing colorectal cancer surgery: A propensity score matching study. Front Nutr 2023; 10:1040893. [PMID: 37006941 PMCID: PMC10060866 DOI: 10.3389/fnut.2023.1040893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 03/06/2023] [Indexed: 03/17/2023] Open
Abstract
IntroductionThe clinical utility of glutamine in patients undergoing colorectal cancer (CRC) surgery remains unclear. Therefore, we aimed to investigate the impact of postoperative treatment with glutamine on postoperative outcomes in patients undergoing CRC surgery.MethodsWe included patients with CRC undergoing elective surgery between January 2014 and January 2021. Patients were divided into the glutamine and control groups. We retrospectively analyzed postoperative infections complications within 30 days and other outcomes using propensity score matching and performed between-group comparisons.ResultsWe included 1,004 patients who underwent CRC surgeries; among them, 660 received parenteral glutamine supplementation. After matching, there were 342 patients in each group. The overall incidence of postoperative complications was 14.9 and 36.8% in the glutamine and control groups, respectively, indicating that glutamine significantly reduced the incidence of postoperative complications [p < 0.001; risk ratio (RR) 0.41 [95% CI 0.30–0.54]]. Compared with the control group, the glutamine group had a significantly lower postoperative infection complications rate (10.5 vs. 28.9%; p < 0.001; RR 0.36 [95% CI 0.26–0.52]). Although there was no significant between-group difference in the time to first fluid diet (p = 0.052), the time to first defecation (p < 0.001), first exhaust (p < 0.001), and first solid diet (p < 0.001), as well as hospital stay (p < 0.001) were significantly shorter in the glutamine group than in the control group. Furthermore, glutamine supplementation significantly reduced the incidence of postoperative intestinal obstruction (p = 0.046). Moreover, glutamine supplementation alleviated the decrease in albumin (p < 0.001), total protein (p < 0.001), and prealbumin levels (p < 0.001).ConclusionsTaken together, postoperative parenteral glutamine supplementation can effectively reduce the incidence of postoperative complications, promote the recovery of intestinal function, and improve albumin levels in patients undergoing CRC surgery.
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Mortada H, Alhindi N, Abukhudair A, Alanazi S, AlSahli A, Arab K. The Effects of Glutamine Supplementation on Reducing Mortality and Morbidity among Burn Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials. JPRAS Open 2022; 35:6-17. [PMID: 36578449 PMCID: PMC9791694 DOI: 10.1016/j.jpra.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/29/2022] [Indexed: 11/27/2022] Open
Abstract
Glutamine (GLN) has been proven to improve the prognosis of severely burned patients. GLN supplementation in critical illness has gained extreme popularity among researchers over the years, and its safety and efficacy are still under question. Therefore, we aim to study the role of GLN supplements in decreasing mortality, length of hospitalization (LOH), and infection in severely burned patients. PRISMA guidelines were used to design and conduct this systematic review. MEDLINE, Cochrane, and EMBASE databases were used to search for randomized controlled trials (RCTs) in January 2022. In order to assist in the search, MeSH terms such as burn injury, GLN, and RCT were used. As a result of reviewing the literature, 1112 publications were found. We included only 7 RCTs after implanting our inclusion criteria. There were 328 patients enrolled in the study, with 166 patients (50.61%) were allocated to GLN supplementation and 162 patients in the control groups (49.39%). The risk of infection was significantly lower among patients who received GLN supplementation than those in the control groups (RR = 0.41, 95% CI, 0.18 to 0.92, p = 0.030). The risk of death was significantly lower among GLN-receiving patients compared to non-GLN-receiving patients (RR = 0.09, 95% CI, 0.01 to 0.63, p = 0.016). GLN supplementation has been linked to lower hospital mortality and infection-related morbidity in burn patients. Furthermore, larger-scale and higher-quality studies are needed to assess whether there are any statistically and clinically significant changes.
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Affiliation(s)
- Hatan Mortada
- Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University and Department of Plastic Surgery & Burn Unit, King Saud Medical City, Riyadh, Saudi Arabia,Corresponding author: Hatan Mortada, Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University, and Department of Plastic Surgery & Burn unit, King Saud Medical City, Riyadh, Saudi Arabia. PO Box 12161, Saudi Arabia, Mobile: 00966 54 668 0755
| | - Nawaf Alhindi
- Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
| | | | - Shahad Alanazi
- Division of Plastic Surgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Alaa AlSahli
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Khalid Arab
- Division of Plastic Surgery, Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Hu Y, Thaler J, Nieuwland R. Extracellular Vesicles in Human Milk. Pharmaceuticals (Basel) 2021; 14:1050. [PMID: 34681274 PMCID: PMC8539554 DOI: 10.3390/ph14101050] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/05/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022] Open
Abstract
Milk supports the growth and development of infants. An increasing number of mostly recent studies have demonstrated that milk contains a hitherto undescribed component called extracellular vesicles (EVs). This presents questions regarding why milk contains EVs and what their function is. Recently, we showed that EVs in human milk expose tissue factor, the protein that triggers coagulation or blood clotting, and that milk-derived EVs promote coagulation. Because bovine milk, which also contains EVs, completely lacks this coagulant activity, important differences are present in the biological functions of human milk-derived EVs between species. In this review, we will summarize the current knowledge regarding the presence and biochemical composition of milk EVs, their function(s) and potential clinical applications such as in probiotics, and the unique problems that milk EVs encounter in vivo, including survival of the gastrointestinal conditions encountered in the newborn. The main focus of this review will be human milk-derived EVs, but when available, we will also include information regarding non-human milk for comparison.
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Affiliation(s)
- Yong Hu
- Laboratory of Experimental Clinical Chemistry and Vesicle Observation Center, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;
- Biomedical Engineering & Physics, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Johannes Thaler
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria;
| | - Rienk Nieuwland
- Laboratory of Experimental Clinical Chemistry and Vesicle Observation Center, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;
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Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the Intestinal Mucosa During Sepsis. Front Immunol 2019; 10:891. [PMID: 31114571 PMCID: PMC6502990 DOI: 10.3389/fimmu.2019.00891] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 04/08/2019] [Indexed: 12/12/2022] Open
Abstract
Sepsis is a complex of life-threating organ dysfunction in critically ill patients, with a primary infectious cause or through secondary infection of damaged tissues. The systemic consequences of sepsis have been intensively examined and evidences of local alterations and repercussions in the intestinal mucosal compartment is gradually defining gut-associated changes during sepsis. In the present review, we focus on sepsis-induced dysfunction of the intestinal barrier, consisting of an increased permeability of the epithelial lining, which may facilitate bacterial translocation. We discuss disturbances in intestinal vascular tonus and perfusion and coagulopathies with respect to their proposed underlying molecular mechanisms. The consequences of enzymatic responses by pancreatic proteases, intestinal alkaline phosphatases, and several matrix metalloproteases are also described. We conclude our insight with a discussion on novel therapeutic interventions derived from crucial aspects of the gut mucosal dynamics during sepsis.
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Affiliation(s)
- Felix Haussner
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Shinjini Chakraborty
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Rebecca Halbgebauer
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
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Meena AS, Shukla PK, Sheth P, Rao R. EGF receptor plays a role in the mechanism of glutamine-mediated prevention of alcohol-induced gut barrier dysfunction and liver injury. J Nutr Biochem 2018; 64:128-143. [PMID: 30502657 DOI: 10.1016/j.jnutbio.2018.10.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 10/20/2018] [Accepted: 10/30/2018] [Indexed: 12/12/2022]
Abstract
Recent study indicated that glutamine prevents alcoholic tissue injury in mouse gut and liver. Here we investigated the potential role of Epidermal Growth Factor Receptor (EGFR) in glutamine-mediated prevention of ethanol-induced colonic barrier dysfunction, endotoxemia and liver damage. Wild-type and EGFR*Tg transgenic (expressing dominant negative EGFR) mice were fed 1-6% ethanol in Lieber-DeCarli diet. Gut permeability was measured by vascular-to-luminal flux of FITC-inulin, and junctional integrity assessed by confocal microscopy. Liver injury was evaluated by plasma transaminases, histopathology and triglyceride analyses. Glutamine effect on acetaldehyde-induced tight junction disruption was investigated in Caco-2 cell monolayers. Doxycycline-induced expression of EGFR* blocked glutamine-mediated prevention of ethanol-induced disruption of colonic epithelial tight junction, mucosal permeability and endotoxemia. Ethanol activated cofilin and disrupted actin cytoskeleton, which was blocked by glutamine in an EGFR-dependent mechanism. Ethanol down-regulated antioxidant gene expression and up-regulated cytokine and chemokine gene expression, which were blocked by glutamine in wild-type mice in the presence or absence of doxycycline, but not in EGFR*Tg mice in the presence of doxycycline. Histopathology, plasma transaminases, triglyceride and expression of chemokine and antioxidant genes indicated ethanol-induced liver damage, which were blocked by glutamine in an EGFR-dependent mechanism. Src kinase activity and extracellular ligand binding domain of EGFR are required for glutamine-mediated protection of barrier function in Caco-2 cell monolayers. Glutamine released metalloproteinases into the medium, and metalloproteinase inhibitors blocked glutamine-mediated protection of barrier function. Results demonstrate that EGFR plays an important role in glutamine-mediated prevention of alcoholic gut permeability, endotoxemia and liver damage.
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Affiliation(s)
- Avtar S Meena
- Department of Physiology, University of Tennessee Health Science Center, 3 Dunlap Street, Suite S303, Memphis, TN 38103
| | - Pradeep K Shukla
- Department of Physiology, University of Tennessee Health Science Center, 3 Dunlap Street, Suite S303, Memphis, TN 38103
| | - Parimal Sheth
- Department of Physiology, University of Tennessee Health Science Center, 3 Dunlap Street, Suite S303, Memphis, TN 38103
| | - RadhaKrishna Rao
- Department of Physiology, University of Tennessee Health Science Center, 3 Dunlap Street, Suite S303, Memphis, TN 38103.
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Varga G, Lajkó N, Ugocsai M, Érces D, Horváth G, Tóth G, Boros M, Ghyczy M. Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound. Eur J Pharmacol 2016; 781:181-9. [PMID: 27079640 DOI: 10.1016/j.ejphar.2016.04.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 04/04/2016] [Accepted: 04/11/2016] [Indexed: 01/08/2023]
Abstract
Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim was to develop a new compound from ASA and Tris precursors and to characterize the biological effects of ASA-Tris and the derivatives ASA-bis- and mono-hydroxymethyl-aminomethane (ASA-Bis, ASA-Mono, respectively) using in vivo and in vitro test systems. ASA or ASA conjugates (0.55mmol/kg, each) were administered intragastrically to Sprague-Dawley rats. Changes in the mucosal structure and in the serosal microcirculation were detected by in vivo imaging techniques, the plasma TNF-alpha, tissue xanthine oxidoreductase and myeloperoxidase activities, and liver cytochrome c changes were also determined. In two separate series, platelet aggregation and carrageenan arthritis-induced inflammatory pain were measured in control, ASA and ASA-Tris-treated groups. Severe mucosal injury and a significant decrease in serosal red blood cell velocity developed in the ASA-treated group and an ~2-fold elevation in proinflammatory mediator levels evolved. ASA-Tris did not cause bleeding, microcirculatory dysfunction, mucosal injury or an elevation in proinflammatory markers. The ASA-Mono and ASA-Bis conjugates did not cause macroscopic bleeding, but the inflammatory activation was apparent. ASA-Tris did not influence the cyclooxygenase-induced platelet aggregation significantly, but the inflammatory pain was reduced as effectively as in the case of equimolar ASA doses. ASA-Tris conjugation is an effective approach through which the GI side-effects of ASA are controlled by decreasing the cytokine-mediated progression of pro-inflammatory events.
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Affiliation(s)
- Gabriella Varga
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, H-6720, Szeged, Szőkefalvi-Nagy Béla u. 6, Hungary.
| | - Norbert Lajkó
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, H-6720, Szeged, Szőkefalvi-Nagy Béla u. 6, Hungary.
| | - Melinda Ugocsai
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, H-6720, Szeged, Szőkefalvi-Nagy Béla u. 6, Hungary.
| | - Dániel Érces
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, H-6720, Szeged, Szőkefalvi-Nagy Béla u. 6, Hungary.
| | - Gyöngyi Horváth
- Department of Physiology, Faculty of Medicine, University of Szeged, H-6720, Szeged, Dóm tér 10, Hungary.
| | - Gábor Tóth
- Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720, Szeged, Dóm tér 8, Hungary.
| | - Mihály Boros
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, H-6720, Szeged, Szőkefalvi-Nagy Béla u. 6, Hungary.
| | - Miklós Ghyczy
- Pax Forschung GmbH, Im Rapsfeld 23, 50933 Cologne, Germany.
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Jeurnink SM, Nijs MM, Prins HAB, Greving JP, Siersema PD. Antioxidants as a treatment for acute pancreatitis: A meta-analysis. Pancreatology 2015; 15:203-8. [PMID: 25891791 DOI: 10.1016/j.pan.2015.03.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 03/10/2015] [Accepted: 03/16/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess the efficacy of antioxidants in acute (AP) pancreatitis. METHODS We searched PubMed, Embase and the Cochrane library for all randomized controlled trials (RCT) involving administration of antioxidants in the therapy of AP until February 2012. AP studies were pooled to analyze the effect of antioxidants on hospital stay, mortality, and complications. Subgroup analyses were performed on the use of the antioxidant glutamine. RESULTS In total, eleven RCTs were included. Among patients with AP, antioxidant therapy resulted in a borderline significant reduction in hospital stay (mean difference -1.74; 95%CI -3.56 to 0.08), a significant decrease in complications (RR 0.66; 95%CI 0.46-0.95) and a non-significant decrease in mortality rate (RR 0.66; 95%CI 0.30-1.46). Subgroup analyses showed that glutamine significantly reduced complications (RR 0.51; 95%CI 0.34-0.78) and mortality rate (RR 0.33; 95%CI 0.13-0.85). CONCLUSION The present meta-analysis shows a possible benefit of glutamine supplementation in patients with acute pancreatitis. However, large randomized trials are needed to confirm these observations.
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Affiliation(s)
- S M Jeurnink
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands.
| | - M M Nijs
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - H A B Prins
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
| | - J P Greving
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - P D Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
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Parenteral glutamine supplementation has no effect on chemotherapy-induced toxicity in children with non-Hodgkin lymphoma. J Pediatr Hematol Oncol 2013; 35:371-6. [PMID: 23426005 DOI: 10.1097/mph.0b013e318282daf4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
PURPOSE Protecting patients from the acute and/or chronic toxicity of antineoplastic therapy has become a major concern of oncology centers around the world. Glutamine has been used as a multisystemic protective agent to minimize the side effects arising from the treatment of childhood cancers. In this study, the effect of intravenous glutamine supplementation was investigated in children receiving chemotherapy for non-Hodgkin lymphoma. METHODS Twelve children, of 48 to 120 months of age, and who had non-Hodgkin lymphoma were enrolled in the study. Thirty chemotherapy courses were given in combination with glutamine, and 31 chemotherapy courses were given without glutamine. Glutamine was given intravenously for 7 days, at a dose of 0.4 g/kg/d. Patients were evaluated in each course with regard to gastrointestinal, mucosal, and hematological toxicities. RESULTS There were no significant differences in the hematological parameters between the 2 groups. The requirements for red blood cells and platelets during the chemotherapy courses were similar in both groups (P=0.64 and 0.40, respectively). Patients supplemented with glutamine developed mucositis in 21 of 30 courses (70%) and patients without glutamine supplements developed mucositis in 23 of 31 courses (74%). The mean duration of mucositis and the mean mucositis score in each course were similar between the 2 groups. In addition, gastrointestinal system and hepatic toxicity did not differ between groups. The mean duration of febrile neutropenia and the length of hospitalization were also similar in both groups (P=0.09 and 0.13, respectively). CONCLUSIONS Parenteral glutamine supplementation has no effect on mucositis, fever and febrile neutropenia, length of hospitalization, red blood cell, and platelet requirements, and hematological, gastrointestinal, and hepatic toxicities in children receiving severe chemotherapy.
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Benjamin J, Makharia G, Ahuja V, Anand Rajan KD, Kalaivani M, Gupta SD, Joshi YK. Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial. Dig Dis Sci 2012; 57:1000-1012. [PMID: 22038507 DOI: 10.1007/s10620-011-1947-9] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2011] [Accepted: 10/08/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn's disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP. AIM We evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD. METHODS In a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5 g/kg ideal body weight/day for 2 months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system. RESULTS Patients (age 34.5 ± 10.5 years; 20 males) were assigned to the GG (n = 15) or ACG (n = 15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2 months was 0.029 (0.006-0.090) and 0.033 (0.009-0.077), respectively, with P = 0.6133. IP normalized in 8 (57.1%) patients in each group (P = 1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2 months was 2.68 (1.02) and 2.49 (0.67), respectively, (P = 0.347). At the end of 2 months LMR improved significantly in GG from 0.071 (0.041-0.254) to 0.029 (0.006-0.090) (P = 0.0012) and in ACG from 0.067 (0.040-0.136) to 0.033 (0.009-0.077) (P = 0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P = 0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P = 0.009). CONCLUSIONS Intestinal permeability and morphology improved significantly in both glutamine and ACG.
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Affiliation(s)
- Jaya Benjamin
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
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Wang F, Zhao HY, Zhang ST, Gong YZ, Zhang HF, Zhang C. Effect of enteral nutrition on dextran sulfate sodium-induced colitis in rats. J Dig Dis 2011; 12:453-8. [PMID: 22118695 DOI: 10.1111/j.1751-2980.2011.00518.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVE To study the effect of enteral nutrition (EN) on dextran sulfate sodium (DSS)-induced colitis in rats. METHODS Eighty-four Sprague-Dawley rats were divided into 7 groups (12 rats in each group). The blank control group was given ordinary laboratory feed and drinking water. The experimental groups received 5% DSS as drinking water for 7 days. Of the experimental groups, the model control group received ordinary laboratory feed, protein based enteral nutrition (PEN) was fed in the PEN group, while other groups received ordinary laboratory feed plus 5-aminosalicylic acid (5-ASA), methyl-prednisolone, Lactobacillus or glutamine, respectively. On the 8th day, all the rats were sacrificed. Inflammatory scores were assessed from colonic mucosa. Blood culture from inferior vena cava, fecal culture and secretary immunoglobulin-A (S-IgA) levels from colonic contents were determined. RESULTS Colon inflammatory scores of Lactobacillus, PEN, glutamine and drug-treated groups were lower than that of the model control group (P < 0.01). The ratios of bacteria translocation in the EN (PEN, Lactobacillus and glutamine) groups were lower than that in the model control group (P < 0.0083). Fecal Lactobacilli in the Lactobacillus and glutamine groups were higher than that in the model control group (P < 0.05). S-IgA levels in colonic contents of the PEN and 5-ASA group were lower than that in the model control group (P < 0.05). CONCLUSIONS EN is an effective therapy for treating DDS-induced colitis. EN could alleviate damage, promote the repair of colonic epithelial cells and inhibit bacterial translocation. Lactobacillus and glutamine could also increase the Lactobacilli in colon.
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Affiliation(s)
- Fang Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing Digestive Disease Center, Beijing, China
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Oláh A, Romics L. Evidence-based use of enteral nutrition in acute pancreatitis. Langenbecks Arch Surg 2010; 395:309-16. [PMID: 20309576 DOI: 10.1007/s00423-010-0631-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Accepted: 03/02/2010] [Indexed: 02/06/2023]
Abstract
PURPOSE A systematic review was carried out to analyze current evidence-based data on the use of enteral nutrition in the management of acute pancreatitis. METHODS Literature search was performed on "Pubmed" and "Medline" databases to identify articles investigating the role and potential effect of enteral nutrition on the outcome of patients with acute pancreatitis. Relevant data were analyzed from the viewpoints of possible benefits and complications, route and timing of administration, and composition of nutrients. RESULTS Thirty-two prospective randomized controlled trials and 15 meta-analyses of those were identified and included in this overview. Strong evidence suggests that enteral nutrition significantly reduces mortality rate of severe acute pancreatitis. While both nasogastric and nasojejunal feeding appear to be safe in severe pancreatitis, early low-fat oral diet is possibly beneficial in patients with mild pancreatitis. Since maintenance of the gut barrier function is one of the crucial effects of enteral nutrition, enteral feeding should be commenced within the first 24 h after hospital admission, in order to prevent early bacterial translocation. However, it seems that neither immunonoenhanced nutrients nor probiotic supplementation are able to reduce mortality further, and--therefore--cannot be recommended for patients with acute pancreatitis. CONCLUSION Although enteral nutrition is undoubtedly a key component of the management of acute pancreatitis, the exact role of that is needed to be defined yet. In particular, conflicting data from studies on nutrient compositions will require further clarification in the future.
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Affiliation(s)
- Attila Oláh
- Department of Surgery, Petz Aladár Teaching Hospital, 9002, Gyor, P.O. Box 92, Hungary.
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Deng ZY, Guo GH, Xing JJ, Zhao XL, Cui Q, Yang Y. Effects of early enteral glutamine supplementation on lymphocyte subpopulations in Peyer's patches in scalded rats. Shijie Huaren Xiaohua Zazhi 2009; 17:2679-2685. [DOI: 10.11569/wcjd.v17.i26.2679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the changes in the number of total lymphocytes and each lymphocyte subpopulation in Peyer's patches in scalded rats receiving different nutrition support, and examine the effects of glutamine (Gln) supplementation on intestinal immunity.
METHODS: Healthy adult Sprague-Dawley rats were subjected to a 30% TBSA third-degree scald injury to induce scald injury. Scalded rats were randomly divided into standard enteral nutrition group (EN group) and glutamine supplementation group (EN plus Gln group). Rats in the EN group were fed standard enteral nutrition (Nutrison Multi Fibre) while those in the EN plus Gln group were fed standard enteral nutrition plus Gln. The number of total lymphocytes and each lymphocyte subpopulation in Peyer's patches were then determined by flow cytometry on days 1, 4, 7 and 10 after feeding.
RESULTS: The number of total lymphocytes, especially B lymphocytes, in Peyer's patches significantly decreased in response to scald induction. The number of total lymphocytes in Peyer's patches in rats in the EN plus Gln group, but not in the EN group, returned to normal on day 7 after scald induction [(5.29 ± 1.03) × 106vs (6.13 ± 1.14) × 106, P > 0.05]. The total number of B cells in Peyer's patches in rats in the EN plus Gln group on days 7 and 10 showed no significant changes when compared with pre-induction value [(2.87 ± 0.69) × 106 and (3.05 ± 0.72) × 106vs (3.29 ± 0.62) × 106, respectively; both P> 0.05]. In contrast, the total number of B cells in Peyer's patches in rats in the EN group on day 10 was significantly lower than pre-induction value [(2.07 ± 0.63) × 106vs (3.29 ± 0.62) × 106; P < 0.05]. Scald induction had no significant effect on the number of CD4+ and CD8+ lymphocytes (both P > 0.05).
CONCLUSION: The number of total lymphocytes decreases significantly in response to scald induction. Early enteral glutamine supplementation can promote lymphocyte proliferation, increase the number of total lymphocytes (especially B cells) in Peyer's patches, and enhance intestinal immunity in scalded rats.
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Pattanshetti VM, Powar RS, Godhi AS, Metgud SC. Enteral glutamine supplementation reducing infectious morbidity in burns patients: a randomised controlled trial. Indian J Surg 2009; 71:193-7. [PMID: 23133153 DOI: 10.1007/s12262-009-0056-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2008] [Accepted: 03/08/2009] [Indexed: 11/28/2022] Open
Abstract
PURPOSE Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients, but their effect on patients with burns is not completely studied. The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity and in turn, the hospital-stay in patients with burns. METHODS Thirty patients with burns were randomly divided into two groups with 15 patients in each, the study (glutamine supplemented) and control group. Patients were randomised to receive either isonitrogenous mixture without glutamine or isonitrogenous mixture with glutamine until complete healing of the burn wound occurred. Incidence of positive blood culture, wound culture, total leucocyte count, hospital-stay and mortality was recorded. RESULTS The results showed that the incidence of positive blood culture was considerably reduced in the study group (0.20±0.41) vs. control (0.73±0.96; p = 0.065). The incidence of positive wound culture was significantly reduced in the study group (1.00 ± 1.25) vs. control (3.53 ± 2.47; p = 0.001). In addition, the wound healing was better and hospital-stay days were reduced in the study group (22.73 ± 9.13 days) vs. (39.73 ± 18.27 days; p = 0.003). CONCLUSIONS These results indicate that enteral glutamine supplementation in adult burn patients could abate the degree of infectious morbidity and reduce hospital-stay.
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Medeiros AC, Chacon DA, Sales VSF, Egito EST, Brandão-Neto J, Pinheiro LAM, Carvalho MR. Glucan and Glutamine Reduce Bacterial Translocation in Rats Subjected to Intestinal Ischemia–Reperfusion. J INVEST SURG 2009; 19:39-46. [PMID: 16546928 DOI: 10.1080/08941930500444453] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Intestinal ischemia/reperfusion (I/R) may induce bacterial translocation (BT). Glutamine (GLN)-enriched nutrition decreases BT. However, little is known about the effect of glucan (GL) in BT. This study investigated the combined effect of GL/GLN on BT, intestinal damage, and portal blood cytokines in animals under I/R. Four groups of 10 rats each were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. The control group (group 1) received only rat food/water, group 2 received glutamine via gavage, group 3 received subcutaneuos soluble (1, 3)-d-glucan, and group 4 received GL + GLN. A sham group (group 5) served as a normal control. Bacterial cultures of ileum, mesenteric lymph nodes (MLN), liver and lung biopsies, histological changes of ileum, and serum cytokines variables were examined after I/R. Data were analyzed by analysis of variance (ANOVA) and the Newman-Keuls test. Results showed that GLN, GL, and GL/GLN significantly reduced BT to MLN, liver, and lung. BT was more attenuated after GL treatment than GLN (P < .05). Rats treated with both GL and GLN exhibited lower bacterial colony counts than the ones treated only with GLN or GL. Severe mucosal damage on histological findings was shown in group 1, but these findings were significantly ameliorated (P < .05) in groups 3 and 4. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels in portal serum were significantly reduced and IL-10 was increased by GL and GLN treatment. In conclusion, the use of GL was more effective than GLN in reducing BT, intestinal damage, and cytokine levels after I/R. Additionally, the combination of GL and GLN improved results.
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Affiliation(s)
- Aldo Cunha Medeiros
- Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
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Abstract
Acute pancreatitis can lead to bowel dysfunction, including the intestinal barrier injury and intestinal motility disorder. A large number of pathogenic bacteria will breed and transfer to other organs through the damaged intestinal mucosa, which can aggravate pancreatitis and cause multiple organ dysfunctions. In this paper, the pathogenesis and treatment of acute pancreatitis with intestinal dysfunction are summarized.
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Oláh A, Romics L. Early enteral nutrition in acute pancreatitis--benefits and limitations. Langenbecks Arch Surg 2008; 393:261-9. [PMID: 18266002 DOI: 10.1007/s00423-008-0291-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2008] [Accepted: 01/21/2008] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The application of enteral feeding as part of the treatment of acute pancreatitis goes back more than a decade now. In this review, the authors outline the indications and limitations of enteral feeding in the treatment of acute pancreatitis using up-to-date evidence-based data. RESULTS AND DISCUSSION Latest meta-analyses suggest that early enteral feeding reduces effectively the incidence of infective complications and shortens hospital stay. In addition, recently published randomized controlled trials indicate that it may reduce mortality as well. CONCLUSION However, the role of immune-enhancing ingredients, such as glutamine or omega-3 fatty acids, combined with enteral nutrition is uncertain, and the published studies are too few to make any treatment recommendation. Supplementation of enteral feeding with probiotics is a potentially promising alternative, but further well-designed multi-centric trials are necessary to prove their role in the treatment of acute pancreatitis.
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Affiliation(s)
- Attila Oláh
- Department of Surgery, Petz Aladár Teaching Hospital, Gyor, Hungary.
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Petrov MS, Atduev VA, Zagainov VE. Advanced enteral therapy in acute pancreatitis: is there a room for immunonutrition? A meta-analysis. Int J Surg 2008; 6:119-24. [PMID: 18325863 DOI: 10.1016/j.ijsu.2008.01.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2008] [Accepted: 01/15/2008] [Indexed: 01/16/2023]
Abstract
BACKGROUND It is believed that certain nutrients such as glutamine, arginine and omega-3 fatty acids may play a significant role in metabolic, inflammatory, and immune processes in acute pancreatitis. The present systematic review aimed to define whether the addition of these substances to enteral nutrition provides any clinical benefit over standard enteral formulas in patients with acute pancreatitis. METHODS A computerized search on electronic databases (Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE) and manual search of the abstracts of major gastroenterological meetings (UEGW, DDW) were undertaken. The studied outcomes were total infectious complication, in-hospital mortality and length of hospital stay. The data were meta-analyzed using a random-effects model. RESULTS A total of three randomized controlled trials satisfied the inclusion criteria. When compared with standard enteral nutrition, immunonutrition was not associated with the significantly reduced risk of total infectious complications (risk ratio 0.82; 95% confidence interval 0.44-1.53; P=0.53) and death (risk ratio 0.64; 95% confidence interval 0.20-2.07; P=0.46). Mean difference in length of hospital stay between two groups was not significant (P=0.80). CONCLUSIONS There is no evidence that enteral nutrition supplemented with glutamine, arginine and/or omega-3 fatty acids, in comparison with standard enteral nutrition, has any beneficial effect on infectious complications, mortality or length of hospital stay in acute pancreatitis. The pursuit of new compositions of enteral formulations in this category of patients may be advocated.
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Affiliation(s)
- Maxim S Petrov
- Department of Surgery, Nizhny Novgorod State Medical Academy, PO Box 568, Nizhny Novgorod 603000, Russia.
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Zhang XP, Zhang J, Song QL, Chen HQ. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier. J Zhejiang Univ Sci B 2007; 8:888-95. [PMID: 18257123 PMCID: PMC2100161 DOI: 10.1631/jzus.2007.b0888] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2007] [Accepted: 10/15/2007] [Indexed: 01/30/2023]
Abstract
Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gut-origin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP's severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP's process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemic reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.
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Affiliation(s)
- Xi-ping Zhang
- Department of General Surgery, Hangzhou First People's Hospital, Hangzhou, China.
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Xue H, Song D, Shi B, Li Y, Li J. Tracking of Green Fluorescent Protein Labeled Escherichia coli Confirms Bacterial Translocation in Blind Loop Rat. J Surg Res 2007; 143:206-10. [PMID: 17720193 DOI: 10.1016/j.jss.2006.03.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2005] [Revised: 03/07/2006] [Accepted: 03/22/2006] [Indexed: 11/30/2022]
Abstract
BACKGROUND Previous investigators have documented small intestinal mucosal injury in blind loop rats. However, the definitive evidence of intestinal bacterial translocation in blind loop animals has been lacking. The purpose of this study was to confirm bacterial translocation in blind loop rats and to evaluate the preventive effect of glutamine on bacterial translocation caused by blind loops. MATERIALS AND METHODS Escherichia coli TG1 labeled with green fluorescent protein was used to track bacterial translocation by gavage to rats. Six groups (n = 10) of rats were studied: unoperated control rats; rats with self-emptying blind loop; rats with self-filling blind loop; unoperated control rats treated with glutamine, 400 mg/d; rats with self-emptying blind loop treated with glutamine, 400 mg/d; rats with self-filling blind loop treated with glutamine, 400 mg/d. Representative tissue specimens of the mesenteric lymph nodes, liver, spleen, and kidney were aseptically harvested for bacteria culture. RESULTS Bacteria were detected in extraintestinal organs of rats with self-emptying blind loop, self-filling blind loop, and self-filling blind loop treated with glutamine. By fluorescence microscope and XbaI restriction digestion analysis, we elucidated that the bacteria isolated from extraintestinal organs were the same bacteria we gavaged to the rats. CONCLUSION We confirmed bacterial translocation in self-filling blind loop and self-emptying blind loop rats. In addition, we also showed that glutamine prevents bacterial translocation in self-emptying blind loop rats.
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Affiliation(s)
- Hua Xue
- Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
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Feng D, Xu W, Chen G, Hang C, Gao H, Yin H. Influence of glutamine on intestinal inflammatory response, mucosa structure alterations and apoptosis following traumatic brain injury in rats. J Int Med Res 2007; 35:644-56. [PMID: 17900404 DOI: 10.1177/147323000703500509] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) -1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.
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Affiliation(s)
- D Feng
- Department of Neurosurgery, Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu Province, China.
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Salman B, Oguz M, Akmansu M, Bebitoglu I, Akca G, Sultan N, Emre U, Kerem M, Yilmaz U. Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation. Adv Ther 2007; 24:648-61. [PMID: 17660176 DOI: 10.1007/bf02848790] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Intestinal mucosal damage and bacterial translocation are clinical problems that may be caused by the use of ionizing radiation. Glutamine (Gln) support reduces the mucosal barrier in several ways. This study was undertaken to investigate the effect of timing of Gln-enriched enteral nutrition (EN) on bacterial translocation and mucosal damage due to radiotherapy (RT). A rat model of whole body irradiation was designed in which a single dose of 485 cGy was given. A total of 50 rats were randomly assigned to the following 5 groups, each of which comprised 10 rats: (1) balanced rat chow given for 8 days without RT (group 1); (2) balanced rat chow given 4 days before and 4 days after RT (group 2); (3) Gln-enriched EN given 4 days before RT (group 3); (4) Gln;enriched EN given 4 days after RT (group 4); and (5) Gln-enriched EN given 4 days before and 4 days after RT (group 5). Mesenteric lymph node and ileum samples were removed for evaluation of bacterial translocation (BT) and histopathologic investigation, respectively. BT and intestinal mucosal injury scores in all rats that received RT were higher than in rats without RT. No difference was seen in parameters between groups 3 and 4 (P>.05, P>.016, respectively); BT and intestinal mucosal injury scores of group 5 were significantly lower than those of groups 3 and 4 (P<.05, P<.016, respectively). Meanwhile, the BT and mesenteric injury scores of group 5 were significantly lower than those of group 2 (P<.05, P<.016, respectively). As a result, intestinal injury due to RT was significantly decreased by Gln-enriched EN support given before and after whole body RT.
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Affiliation(s)
- Bülent Salman
- Department of Surgery, Gazi University Faculty of Medicine, Anakara Turkey.
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Messaris E, Kekis P, Memos N, Chatzigianni E, Menenakos E, Leandros E, Konstadoulakis MM. Sepsis: Prognostic Role of Apoptosis Regulators in Gastrointestinal Cells. World J Surg 2007; 31:787-94. [PMID: 17372670 DOI: 10.1007/s00268-005-0742-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. METHODS Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. RESULTS In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). CONCLUSIONS Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.
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Affiliation(s)
- Evangelos Messaris
- Laboratory of Surgical Research, First Department of Propaedeutic Surgery, Athens Medical School, Hippokration Hospital, 11527 Vas, Sofias Ave 114, Athens, Greece
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Cunha-Lopes WMD, Aguilar-Nascimento JED, Dock-Nascimento D, Gomes-da-Silva MHG, Silva VDATD. Associação de glutamina e probióticos no trofismo mucoso do cólon na peritonite experimental. Rev Col Bras Cir 2007. [DOI: 10.1590/s0100-69912007000100011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
OBJETIVO: O objetivo deste estudo foi investigar o efeito da associação da glutamina e probióticos sobre a mucosa intestinal em ratos submetidos à peritonite experimental. MÉTODO: 16 ratos Wistar (250-350g) com peritonite experimental criada pelo método da punção dupla do ceco foram randomizados para receber diariamente no pós-operatório em conjunto com a dieta, a adição por gavagem de 0,500g de glutamina e leite reconstituído, contendo probióticos (10(6) unidades formadoras de colônias/g de Bifidobacterium lactis BL e Streptococcus thermophilus) (grupo glutamina-probióticos; n=8) ou 0,495g de caseína e leite reconstituído sem probióticos (grupo controle; n=8). O conteúdo das duas dietas foi isonitrogenado e isocalórico. Todos os animais foram sacrificados 120 horas após a peritonite experimental. A profundidade de criptas e espessura de parede da mucosa do cólon foram medidas em biopsias realizadas 2 cm acima da reflexão peritoneal. O restante da mucosa colônica foi pesado e nela mensurou-se o conteúdo de DNA. RESULTADOS: Os animais que receberam glutamina e probióticos apresentaram mucosa mais pesada (0,49±0,12 vs. 0,42±0,07g; p=0,02), maior conteúdo de DNA (0,31±0,07 vs. 0,22±0,05 mg/g de tecido; p<0,01) e criptas mais profundas (272±51 vs. 311±39µ; p=0,04) que o grupo controle. CONCLUSÃO: A associação da glutamina e probióticos confere um maior trofismo na mucosa colônica em ratos submetidos à peritonite experimental.
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Xu XF, Lou WH, Wang DS, Jin DY, Ni XL, Wu ZH. Influence of glutamine on pancreatic blood flow and apoptosis of pancreatic acinar in rats with severe acute pancreatitis. ACTA ACUST UNITED AC 2006; 7:121-6. [PMID: 16643341 DOI: 10.1111/j.1443-9573.2006.00250.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To investigate the role of glutamine on splanchnic blood flow, apoptosis of pancreatic acinar and the underlying mechanism in rats with severe acute pancreatitis. METHODS Forty-eight rats were randomized into two groups: the glutamine group (n = 24) and the severe acute pancreatitis group (n = 24). Jejunotomy was performed in all rats: the glutamine group also received glutamine, and the severe acute pancreatitis group received normal saline. Each group was then subdivided into three subgroups of eight rats each, with the rats be killed at 12, 24 and 36 h after the operation, respectively. A control group underwent sham operation (n = 8). The regional pancreatic microvascular blood flow was measured by Doppler ultrasound. The blood flow of the portal vein, splenic artery and superior mesenteric artery were also recorded. Apoptosis of pancreatic acinar cells was evaluated by TUNEL method. RESULTS The regional pancreatic microvascular blood flow (KHz) decreased significantly in the severe acute pancreatitis group (P < 0.01), and continued to decrease after 24 h (vs. 12 h, P < 0.01). The blood flow of the portal vein, splenic artery and superior mesenteric artery also decreased in the severe acute pancreatitis group. The glutamine group showed increased regional pancreatic microvascular blood flows, as well as increased blood flow of the portal vein, splenic artery and superior mesenteric artery (vs. the severe acute pancreatitis group, P < 0.01). The apoptotic index of pancreatic acinar in the glutamine group was higher than in the severe acute pancreatitis group (P < 0.01), and both were much higher than that in the control group (P < 0.01). CONCLUSIONS Enteral administration of glutamine increased the splanchnic blood flow in severe acute pancreatitis rats. The apoptotic index of pancreatic acinar was negatively correlated with the severity of the disease. The interrelation between glutamine and apoptosis in severe acute pancreatitis is worthy of further investigation.
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Affiliation(s)
- Xue Feng Xu
- Pancreatic Group, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
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Sido B, Seel C, Hochlehnert A, Breitkreutz R, Dröge W. Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci 2006; 51:2170-9. [PMID: 17078002 DOI: 10.1007/s10620-006-9473-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2006] [Accepted: 05/31/2006] [Indexed: 01/01/2023]
Abstract
Intestinal glutamine utilization is integral to mucosal regeneration. We analyzed the systemic and intestinal glutamine status in Crohn's disease (CD) and evaluated the therapeutic effect of glutamine supplementation in an animal model of ileitis. In CD, glutamine concentrations were decreased systemically and in noninflamed and inflamed ileal/colonic mucosa. Mucosal glutaminase activities were depressed in the ileum independent of inflammation but were not different from controls in the colon. In experimental ileitis, oral glutamine feeding prevented macroscopic inflammation, enhanced ileal and colonic glutaminase activities above controls, and normalized the intestinal glutathione redox status. However, glutamine supplementation enhanced myeloperoxidase activity along the gastrointestinal tract and potentiated lipid peroxidation in the colon. In conclusion, glutamine metabolism is impaired in CD. In experimental ileitis, glutamine supplementation prevents inflammatory tissue damage. In the colon, however, which does not use glutamine as its principal energy source, immune enhancement of inflammatory cells by glutamine increases oxidative tissue injury.
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Affiliation(s)
- Bernd Sido
- Department of Surgery, Ruprecht-Karls University, Heidelberg, Germany.
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Schulman AS, Willcutts KF, Claridge JA, Evans HL, Radigan AE, O'Donnell KB, Camden JR, Chong TW, McElearney ST, Smith RL, Gazoni LM, Farinholt HMA, Heuser CC, Lowson SM, Schirmer BD, Young JS, Sawyer RG. Does the addition of glutamine to enteral feeds affect patient mortality? Crit Care Med 2005; 33:2501-6. [PMID: 16276173 DOI: 10.1097/01.ccm.0000185643.02676.d3] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Studies have failed to consistently demonstrate improved survival in intensive care unit (ICU) patients receiving immune-modulating nutrient-enhanced enteral feeds when compared with standard enteral feeds. The objective was to study in a prospective fashion the effects of adding glutamine to standard or immune-modulated (supplemented with omega-3 fatty acids, beta-carotene, and amino acids such as glutamine and arginine) tube feeds. DESIGN Prospective, unblinded study using sequential allocation. SETTING A university surgical trauma ICU. PATIENTS All surgical and trauma patients admitted to the surgical trauma ICU at a university hospital over a 3-yr period who were to receive enteral feeds (n = 185). INTERVENTIONS Sequential assignment to three isocaloric, isonitrogenous diets was performed as follows: standard 1-kcal/mL feeds with added protein (group 1), standard feeds with the addition of 20-40 g/day (0.6 g/kg/day) glutamine (group 2), or an immune-modulated formula with similar addition of glutamine (group 3). The goal for all patients was 25-30 kcal/kg/day and 2 g/kg/day protein. MEASUREMENTS AND MAIN RESULTS Patients were followed until discharge from the hospital. The primary end point was in-hospital mortality, and multiple secondary end points were recorded. In-hospital mortality for group 1 was 6.3% (four of 64) vs. 16.9% (ten of 59, p = .09) for group 2 and 16.1% (ten of 62, p = .09) for group 3. After controlling for age and severity of illness, the difference in mortality between patients receiving standard tube feeds and all patients receiving glutamine was not significant (p < or = .11). There were no statistically significant differences between the groups for secondary end points. CONCLUSIONS The addition of glutamine to standard enteral feeds or to an immunomodulatory formula did not improve outcomes. These findings suggest that enteral glutamine should not be routinely administered to patients with surgical critical illness.
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Targarona Modena J, Barreda Cevasco L, Arroyo Basto C, Orellana Vicuña A, Portanova Ramírez M. Total enteral nutrition as prophylactic therapy for pancreatic necrosis infection in severe acute pancreatitis. Pancreatology 2005; 6:58-64. [PMID: 16327282 DOI: 10.1159/000090024] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2004] [Accepted: 11/05/2004] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the capacity of enteral nutrition, in comparison with the total parenteral nutrition (TPN) plus antibiotic therapy, for avoiding pancreatic necrosis infection in the severe acute pancreatitis. METHODS In the period between October 1998 and September 2003, 87 patients met the inclusion criteria and took part in this research. Within the first week from their admission, 43 patients received TPN and 44 patients received total enteral nutrition (TEN). An adequate prophylactic antibiotic therapy was used in both groups. The severity of the manifestations was similar for both groups having a tomographic 'severity index' of 8 and an entry C-reactive protein of 208 and 203 mg/l, respectively. RESULTS The group that received TPN suffered an organ failure in 79% of the cases, while the percentage showed by the group that received TEN was 31%; 88 and 25% of the patients in each group requiring a surgical intervention, respectively (p < 0.001). There was decreased presence of pancreatic necrosis infection in the group of patients that was supplied with TEN (20%) than in the group receiving TPN, where it reached 74% (p < 0.001). The death rate was significantly higher among the patients who received TPN, (35%), while for the patients who received TEN it was only 5% (p < 0.001). CONCLUSION TEN could be used as a prophylactic therapy for infected pancreatic necrosis since it significantly diminished the necrosis infection as well as the mortality.
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Affiliation(s)
- Javier Targarona Modena
- Department of General Surgery, Edgardo Rebagliati-Martins Hospital, Clinica Anglo Americana, Lima, Perú.
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Nathens AB, Curtis JR, Beale RJ, Cook DJ, Moreno RP, Romand JA, Skerrett SJ, Stapleton RD, Ware LB, Waldmann CS. Management of the critically ill patient with severe acute pancreatitis. Crit Care Med 2005; 32:2524-36. [PMID: 15599161 DOI: 10.1097/01.ccm.0000148222.09869.92] [Citation(s) in RCA: 255] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Acute pancreatitis represents a spectrum of disease ranging from a mild, self-limited course requiring only brief hospitalization to a rapidly progressive, fulminant illness resulting in the multiple organ dysfunction syndrome (MODS), with or without accompanying sepsis. The goal of this consensus statement is to provide recommendations regarding the management of the critically ill patient with severe acute pancreatitis (SAP). DATA SOURCES AND METHODS An international consensus conference was held in April 2004 to develop recommendations for the management of the critically ill patient with SAP. Evidence-based recommendations were developed by a jury of ten persons representing surgery, internal medicine, and critical care after conferring with experts and reviewing the pertinent literature to address specific questions concerning the management of patients with severe acute pancreatitis. DATA SYNTHESIS There were a total of 23 recommendations developed to provide guidance to critical care clinicians caring for the patient with SAP. Topics addressed were as follows. 1) When should the patient admitted with acute pancreatitis be monitored in an ICU or stepdown unit? 2) Should patients with severe acute pancreatitis receive prophylactic antibiotics? 3) What is the optimal mode and timing of nutritional support for the patient with SAP? 4) What are the indications for surgery in acute pancreatitis, what is the optimal timing for intervention, and what are the roles for less invasive approaches including percutaneous drainage and laparoscopy? 5) Under what circumstances should patients with gallstone pancreatitis undergo interventions for clearance of the bile duct? 6) Is there a role for therapy targeting the inflammatory response in the patient with SAP? Some of the recommendations included a recommendation against the routine use of prophylactic systemic antibacterial or antifungal agents in patients with necrotizing pancreatitis. The jury also recommended against pancreatic debridement or drainage for sterile necrosis, limiting debridement or drainage to those with infected pancreatic necrosis and/or abscess confirmed by radiologic evidence of gas or results or fine needle aspirate. Furthermore, the jury recommended that whenever possible, operative necrosectomy and/or drainage be delayed at least 2-3 wk to allow for demarcation of the necrotic pancreas. CONCLUSIONS This consensus statement provides 23 different recommendations concerning the management of patients with SAP. These recommendations differ in several ways from previous recommendations because of the release of recent data concerning the management of these patients and also because of the focus on the critically ill patient. There are a number of important questions that could not be answered using an evidence-based approach, and areas in need of further research were identified.
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Affiliation(s)
- Michael Ellis
- Department of Medicine, Faculty of Medicine and Health Sciences, UAE Medical School, UAE University, Al Ain, United Arab Emirates.
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Abstract
The intestinal barrier function of GI tract is very important in the body except for the function of digestion and absorption. The functional status of gut barrier basically reflects the stress severity when body suffers from trauma and various stimulations. Many harmful factors such as drugs, illnesses, trauma and burns can damage the gut barrier, which can lead to the barrier dysfunction and bacterial/endotoxin translocation. The paper discusses and reviews the concepts, anatomy, pathophysiology of gut barrier and its clinical relations.
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Affiliation(s)
- Lian-An Ding
- Department of General Surgery, Affilitated Hospital of Medical School, Qingdao University, Qingdao 266003, Shandong Province, China.
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Ziegler TR, Evans ME, Fernández-Estívariz C, Jones DP. Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Annu Rev Nutr 2003; 23:229-61. [PMID: 12626687 DOI: 10.1146/annurev.nutr.23.011702.073036] [Citation(s) in RCA: 140] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Intestinal epithelial cell turnover (proliferation, migration, differentiation, and apoptosis) and gut barrier functions are dynamic processes that are markedly affected by nutritional status, the route of feeding, and the adequacy of specific nutrients in the diet. Emerging studies are defining potential therapeutic roles for specific nutrients and diet-derived compounds (including arginine, glutamate, glutamine, glutathione, glycine, vitamin A, zinc, and specific lipids) in gut mucosal turnover, repair, adaptation after massive bowel resection, and barrier function. The role and regulation of endogenous bowel flora in generating short-chain fatty acids from diet-derived fiber and other diet-derived compounds and the effects of these agents on gut function are increasingly being elucidated. Results of these investigations should define new nutritional methods for trophic and cytoprotective effects on the intestine in conditions such as inflammatory bowel disease, malnutrition, and short bowel syndrome.
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Affiliation(s)
- Thomas R Ziegler
- Department of Medicine, Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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35
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Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: A prospective, controlled, randomized clinical trial*. Crit Care Med 2003; 31:2444-9. [PMID: 14530749 DOI: 10.1097/01.ccm.0000084848.63691.1e] [Citation(s) in RCA: 231] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients, but their effect on burn patients is not known. The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity, length of care, and the immune system in burn patients. DESIGN Double-blinded, randomized clinical trial. SETTING Burn center. PATIENTS Forty-five adults with severe burns. INTERVENTIONS Patients were randomized to receive either glutamine or an isonitrogenous control mixture until complete healing occurred. Length of care, incidence of positive blood culture, and mortality were recorded. Phagocytosis by circulating polymorphonuclear cells was measured every 3 days. MEASUREMENTS AND MAIN RESULTS Patient characteristics were similar in both groups. Four patients were excluded from the analysis, because three of them died within 72 hrs and the fourth could not receive enteral nutrition and amino acid supplements for the first 10 days. Of the remaining 41 patients, length of care in the survivors was not different between groups (0.9 vs. 1.0 days/percent total body surface area for glutamine vs. control, respectively), positive blood culture was three times more frequent in control than in glutamine treatment (4.3 vs. 1.2 days/patient, p <.05), and Pseudomonas aeruginosa was detected in six patients on control and zero on glutamine (p <.05). Phagocytosis by polymorphonuclear cells was not different between groups. Mortality rate was significantly lower in glutamine than in control: intention to treat, two vs. 12 (p <.05); per protocol analysis, zero vs. eight (p <.01). CONCLUSIONS Enteral glutamine supplementation in adult burn patients reduces blood infection by a factor of three, prevents bacteremia with P. aeruginosa, and may decrease mortality rate. It has no effect on level of consciousness and does not appear to influence phagocytosis by circulating polymorphonuclear cells.
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Affiliation(s)
- Dominique Garrel
- Burn Centre, Centre Hospitalier de l'Université de Montréal, Hôtel-Dieu, Quebec, Canada.
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Ding LA, Li JS. Effects of glutamine on intestinal permeability and bacterial translocation in TPN-rats with endotoxemia. World J Gastroenterol 2003; 9:1327-32. [PMID: 12800250 PMCID: PMC4611810 DOI: 10.3748/wjg.v9.i6.1327] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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, 1000 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 °C. On day 8, under intra-peritoneal 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.
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Affiliation(s)
- Lian-An Ding
- Clinical College of Nanjing University Medical School, 305 East Zhongshan Road, Nanjing 210002 Jiangsu Province, China.
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Abstract
INTRODUCTION The pathogenesis of acute pancreatitis remains elusive. Sepsis and multiple organ failure continue to cause death (overall mortality rate, approximately 10%) despite immense improvements in supportive, radiologic, and surgical therapy. The gut appears to play a key role in the development of these complications. AIM To critically review the evidence implicating the gut in the pathogenesis of acute pancreatitis. METHODS Relevant English-language literature or abstracts cited in the MEDLINE database were reviewed. RESULTS AND CONCLUSION Gram-negative enteric organisms account for most infections of pancreatic necrosis and subsequent sepsis, which suggests the gut as a source. Intestinal permeability is increased early in patients with severe acute pancreatitis and correlates with endotoxemia, which suggests translocation as a possible mechanism. The pathogenesis of the deranged function of the gut mucosal barrier and the possible sites of increase in intestinal permeability are discussed. The gut also plays a role in priming neutrophils and the release of inflammatory cytokines, which initiate and propagate nearly all the detrimental consequences of severe inflammation and sepsis. Future research avenues and potential therapeutic measures that may restore and preserve gut barrier function are explored.
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Affiliation(s)
- Basil J Ammori
- Division of Surgery, The University of Leeds, and the Center for Digestive Diseases, The General Infirmary, Leeds, United Kingdom.
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Joon Suh G, Youn YK, Song HG, Eui Rhee J, Eun Jung S. The effect of glutamine on inducible nitric oxide synthase gene expression in intestinal ischemia-reperfusion injury. Nutr Res 2003. [DOI: 10.1016/s0271-5317(02)00479-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Dowdall JF, Winter DC, Bouchier-Hayes DJ. Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury. J Surg Res 2002; 108:61-8. [PMID: 12443716 DOI: 10.1006/jsre.2002.6519] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain. MATERIALS AND METHODS This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery. RESULTS Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower. CONCLUSIONS We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.
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Affiliation(s)
- J F Dowdall
- The RCSI Department of Surgery, Beaumont Hospital, Dublin, 9, Ireland.
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40
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Macintire DK, Bellhorn TL. Bacterial translocation: clinical implications and prevention. Vet Clin North Am Small Anim Pract 2002; 32:1165-78. [PMID: 12380171 DOI: 10.1016/s0195-5616(02)00037-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The occurrence of BT has been well documented in experimental animal models of hemorrhagic shock, trauma, severe burns, cirrhosis, pancreatitis, and bacterial overgrowth. Translocation of viable bacteria and endotoxins into mesenteric lymph nodes and other gut-associated lymphatic tissue is thought to activate a complex interplay of mediators that initiates the SIRS. Multiple humoral and cellular systems cause synthesis, expression, and release of inflammatory mediators, such as toxic oxygen radicals, proteolytic enzymes, adherence molecules, and various cytokines. A massive sustained proinflammatory response can ultimately result in irreversible multiple organ dysfunction. Because BT is associated with splanchnic hypoperfusion, the cornerstone of therapy involves rapid resuscitation and restoration of tissue perfusion. If a septic focus can be identified, it should be removed. Gut protectants, promotility agents, antioxidants, and immune-enhancing diets have shown promise in improving length of survival in these critically ill patients.
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Affiliation(s)
- Douglass K Macintire
- Department of Small Animal Surgery and Medicine, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
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41
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Pan M, Wolfgang CA, Karinch AM, Lin C, Meng Q, Vary TC, Souba WW. Protein kinase C activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases. J Surg Res 2002; 106:137-44. [PMID: 12127819 DOI: 10.1006/jsre.2002.6460] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Glutamine is essential for the preservation of intestinal structure and function and its uptake by the bowel is augmented during catabolic states. However, the signal transduction pathways implicated in brush border glutamine transport have not been examined. The aim of this study was to investigate the intracellular signaling pathways involved in the regulation of accelerated intestinal glutamine transport. Our hypothesis was that the activation of intestinal glutamine transport involves protein kinase C (PKC) and is mediated by mitogen-activated protein kinases (MAPKs). METHODS [3H]L-Glutamine (50 microM) transport activity and mRNA levels for the intestinal glutamine transporter ATB(0) were measured in intestinal epithelial Caco-2 cells. Confluent cells were treated with phorbol ester (PMA, 0-10 microM), the MAPK MEK inhibitor PD 98059 (0-100 microM), actinomycin (0-0.1 microM), MAPK p38 inhibitor SB 203580 (0-10 microM), protein kinase C inhibitor chelerythrine chloride (0-6.6 microM), or cycloheximide (0-10 microM) for 24 h. Data were analyzed by ANOVA with significance set at P < 0.05. RESULTS Phorbol ester treatment increased intestinal System B glutamine transport activity by 75%, an increase that was blocked individually by PD 98059, chelerythrine chloride, actinomycin, and cycloheximide, but not SB 203580, an effect first noted at 6 h. The resulting activity increase was consistent with de novo synthesis of transporter units and enhanced expression of transporter gene ATB(0) as indicated by a threefold increase of ATB(0) mRNA levels in PMA-treated cells. CONCLUSIONS Activation of glutamine transport in Caco-2 cells by phorbol ester occurs via signaling pathways that lead to transcription of the glutamine transporter gene. PKC and mitogen-activate protein kinase MEK are key intracellular mediators involved in this signal transduction cascade.
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Affiliation(s)
- Ming Pan
- Department of Surgery, Penn State College of Medicine, Hershey, PA 17033, USA
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Moriguchi T, Hirasawa H, Oda S, Shiga H, Nakanishi K, Matsuda KI, Nakamura M, Yokohari K, Hirano T, Hirayama Y, Watanabe E. A patient with severe acute pancreatitis successfully treated with a new critical care procedure. Ther Apher Dial 2002; 6:221-4. [PMID: 12109947 DOI: 10.1046/j.1526-0968.2002.00435.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic Gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.
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Affiliation(s)
- Takeshi Moriguchi
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
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Salvalaggio PRO, Neto CZ, Tolazzi ARD, Gasparetto EL, Coelho JCU, Campos ACL. Oral glutamine does not prevent bacterial translocation in rats subjected to intestinal obstruction and Escherichia coli challenge but reduces systemic bacteria spread. Nutrition 2002; 18:334-7. [PMID: 11934547 DOI: 10.1016/s0899-9007(01)00750-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE We investigated whether oral glutamine prevents bacterial translocation. METHODS Male Wistar rats were fed with isocaloric and isoproteic standard rat chow and randomly assigned to receive glutamine (GLN) or glycine administered through an orogastric tube at 1.5 g.kg(-1).d(-1) for 7 d. On day 8 of the study, the animals were anesthetized and intestinal obstruction was produced by ligature of the terminal ileum. A suspension containing 10(9) colony-forming units per milliliter of Escherichia coli ATCC 25992 was injected into the lumen of the ileum. Twenty-four hours later, blood was withdrawn, and mesenteric lymph nodes and fragments of spleen, liver, and lung were sent for microbiological analysis. Cultures were done on blood agar and MacConkey agar. Student's t test and analysis of variance between two proportions were used. P < 0.05 was considered significant. RESULTS Rats in both groups lost body weight during the experiment (not significant). Mesenteric lymph node cultures were positive in both groups. The GLN group had a smaller percentage of E. coli in blood and organ cultures (65.45% versus 82.67% in the glycine group; P = 0.027). Positive cultures of blood, spleen, liver and lung also were higher on glycine group, although not significantly. CONCLUSIONS Oral GLN does not prevent bacterial translocation in rats after intestinal obstruction and E. coli challenge. No specific organ was protected by GLN. Nevertheless, its use was associated with a reduced number of positive E. coli cultures in blood and remote organs, and thus diminished bacteria spread. This association suggests a role for GLN in gut barrier protection, possibly by immune system enhancement.
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46
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Zazzo JF. Modalités de la nutrition artificielle au cours des pancréatites aiguës. NUTR CLIN METAB 2001. [DOI: 10.1016/s0985-0562(01)00072-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Abstract
The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.
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Affiliation(s)
- T R Ziegler
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
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Qin RY, Zou SQ, Wu ZD, Qiu FZ. Influence of splanchnic vascular infusion on the content of endotoxins in plasma and the translocation of intestinal bacteria in rats with acute hemorrhage necrosis pancreatitis. World J Gastroenterol 2000; 6:577-580. [PMID: 11819651 PMCID: PMC4723561 DOI: 10.3748/wjg.v6.i4.577] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Abstract
The immediate metabolic response to a septic challenge is probably adaptive, meaning that nutritional interference, mainly via the parenteral route, during this early phase of instability can do more harm than good. During the later phases, a gradual increase in enteral nutrition, at the expense of parenteral nutrition, combined with the administration of nutraceuticals such as glutamine and omega-3 fatty acids, can counteract wasting and modulate the complex inflammatory response and immunosuppression associated with sepsis. In these times of scarce resources, there is an urgent need to clearly document the efficacy of immuno/pharmaconutrients, individually and in combination, enterally or parenterally, before proposing them for routine management of septic patients in the intensive care unit.
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Affiliation(s)
- Gérard Nitenberg
- Department of Anesthesia, Analgesia, Intensive Care and Infectious Diseases, Institut Gustave Roussy, Villejuif, France
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50
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Abstract
In acute pancreatitis, pancreatic inflammation may be complicated by the development of pancreatic infection with a high associated mortality. Pancreatic infection is related to the extent of pancreatic inflammation and necrosis and typically occurs in the second or third week of severe disease. It may be associated with a wide range of Gram-positive and Gram-negative bacteria, notably enterobacteria and also with Candida spp. Current surgical practice in the UK is to use prophylactic antimicrobial therapy in patients with severe disease, with the aim of preventing secondary pancreatic infection. Experimental evidence demonstrates that prophylactic antibacterial therapy prevents pancreatic infection and reduces mortality. Furthermore, studies of antibacterial prophylaxis in patients with acute pancreatitis suggest that prophylactic antibacterial therapy is associated with a reduction in mortality, particularly in those with severe disease. In general, broad-spectrum antibiotics have been used in animal and human studies. However, current evidence does not allow comparisons to be made between different antimicrobial agents. Nutritional strategies may also be important in the prevention of pancreatic infection. Enteral, rather than parenteral, nutrition has been associated with an improved clinical outcome in severe pancreatitis.
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Affiliation(s)
- A O Qamruddin
- Department of Microbiology, Salford Royal Hospitals NHS Trust, Hope Hospital, Salford, M6 8HD
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