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1.
Surg Today ; 46(1): 62-65, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25721172

ABSTRACT

PURPOSES: Although surgery is commonly used to treat parastomal hernia, it is very difficult and has shown poor results. Recently, repair with prosthetic materials has been thought to be a more promising method. METHODS: The Sugarbaker technique with e-PTFE mesh (Dualmesh®) performed via open surgery was adopted for seven patients with parastomal hernia. Two of them were recurrent cases. Three of the patients experienced incarceration of the intestine and recovered conservatively before surgery. The median age of the patients at the parastomal hernia repair was 77.6 years old (range 37.7-84.7). RESULTS: The median operative time was 211 min (range 147-256). The median hernia size was 28 cm2 (range 7.5-60 cm2). The median amount of blood loss during the operation was 158 g (range 0-370 g). Surgical site infection was not observed. The postoperative median hospital stay was 17 days (range 13-40) and the median follow-up was 2.4 years (range 1.0-3.7). During the follow-up period, we did not observe recurrence or readmission. CONCLUSIONS: The surgical results were satisfactory with minimal morbidity and no recurrences. The Sugarbaker technique for parastomal repair using e-PTFE mesh may be suitable as a standard method for treating parastomal hernia.

2.
Nihon Geka Gakkai Zasshi ; 116(2): 94-8, 2015 Mar.
Article in Japanese | MEDLINE | ID: mdl-26050508

ABSTRACT

Various intestinal conditions such as stricture, fistula, abscess, perforation, and hemorrhage are complications of Crohn's disease. Surgical intervention remains important, even in the era of biologic therapy. Limited surgical resection is essential to avoid short bowel syndrome after massive resection or multiple operations. Strictureplasty is effective for short, isolated stricture of the small intestine and provides good results equivalent to those of intestinal resection. Fecal diversion in the case of very complicated lesions not suitable for immediate resection can offer patients general and local improvement. Although bypass surgery is currently not performed because of the possibility of deterioration or carcinogenesis of the bypassed segment, bypass surgery is useful for avoiding stoma. Laparoscopic surgery is indicated for patients with nonperforating, localized ileocecal lesions, and for those presenting initially. The cumulative postoperative reoperation rate is about 50% to 60% at 10 years. The risk factors for early recurrence are smoking, perforating type, previous reoperation, and small intestinal disease. During postoperative follow-up and maintenance treatment, the importance of an algorithm comprising regular check-ups with ileocolonoscopy and the use of thioprines and biologics has been proposed.


Subject(s)
Crohn Disease/surgery , Digestive System Surgical Procedures/methods , Humans , Prognosis , Recurrence , Risk Factors , Surgical Stomas
3.
Surg Today ; 44(2): 340-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23784107

ABSTRACT

PURPOSE: To evaluate the foregut and hindgut hypotheses for metabolic surgery in obese rats with diabetes. METHODS: Otsuka Long-Evans Tokushima fatty rats were divided into a sham operation group, a partial duodeno-jejunal bypass (P-DJB) group, and a complete DJB (C-DJB) group. P-DJB is a model to test foregut hypothesis, whereas C-DJB is a model to test both hypotheses. We performed oral glucose tolerance tests (OGTT) on all groups at baseline, and then 4 and 8 weeks postoperatively. The rats were killed thereafter and the plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured. A separate sub-group of C-DJB rats underwent OGTT after treatment with the GLP-1 antagonist, the PYY antagonist, or saline. RESULTS: Marked improvement of the blood glucose control during the OGTT was noted 8 weeks after C-DJB, but not 8 weeks after P-DJB or the sham operation. The serum GLP-1 and PYY levels were higher in the C-DJB group than in the other two groups. Pretreatment with the GLP-1 antagonist increased the blood glucose levels 30 min after the OGTT in the C-DJB rats. CONCLUSIONS: Improvement in glucose metabolism after DJB was associated with the inflow of bile and pancreatic juice into the ileum, supporting validity of the hindgut hypothesis. GLP-1 appears to play a role in this improvement.


Subject(s)
Bariatric Surgery/methods , Diabetes Mellitus, Type 2/metabolism , Duodenum/surgery , Glucose/metabolism , Jejunum/surgery , Obesity/metabolism , Animals , Bile/metabolism , Blood Glucose/metabolism , Glucagon-Like Peptide 1/blood , Glucagon-Like Peptide 1/physiology , Glucose Tolerance Test , Ileum/metabolism , Male , Pancreatic Juice/metabolism , Peptide YY/metabolism , Peptide YY/physiology , Rats , Rats, Inbred OLETF
6.
Gan To Kagaku Ryoho ; 39(8): 1271-3, 2012 Aug.
Article in Japanese | MEDLINE | ID: mdl-22902457

ABSTRACT

The patient, a 75-year-old woman, who was referred to our hospital in April 2010 because of diarrhea and lower abdominal pain. Abdominal CT scan revealed a large tumor, over 8 cm in diameter within the pelvis, and colonoscopy detected rectal cancer. There was no obvious distant metastasis, although invasion to the uterus and regional lymph node metastasis was suspected. After admission, she had been suffering from tumor-accompanying symptoms such as fever, melena, and abdominal pain. Although loop sigmoid colostomy was performed, symptoms were unimproved, and the tumor had grown to 11 cm in diameter. Therefore, chemotherapy(mFOLFOX6)was started. After two courses of chemotherapy, the tumor-accompanying symptoms improved. Six courses of chemotherapy were administered, and subsequent examination revealed shrinkage of the tumor(effect judgment PR). Thirteen days after final chemotherapy, the tumor was successfully resected. Pathological diagnosis of the surgical specimen was tub2, pSI(sigmoid colon), pN0, and Stage II. The surgical margin was completely free of cancer(R0), and the histological effect of chemotherapy was judged as Grade 1b. The patient had received adjuvant chemotherapy with UFT+LV for half a year after discharge. She has been free from any sign of recurrence for 11 months. This case suggests that appropriate preoperative chemotherapy is useful for locally advanced rectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Aged , Biopsy , Combined Modality Therapy , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Magnetic Resonance Imaging , Neoplasm Invasiveness , Neoplasm Staging , Organoplatinum Compounds/therapeutic use , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery
7.
Surgery ; 151(6): 822-30, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22316438

ABSTRACT

BACKGROUND: Ileal interposition (IT), in which the distal ileum is transposed isoperistaltically into the proximal jejunum, is considered as a procedure for metabolic or antidiabetes surgery. Our aim was to study the effects of IT on glycemic control, fat metabolism, and hormonal changes in obese rats with spontaneous diabetes. METHODS: Animals were divided into either an IT or a sham (SH) group. They underwent an oral glucose tolerance test (OGTT) before and 4 and 8 weeks after the operation. All animals were killed 10 weeks after operation for analyses of tissue weight (liver, pancreas, epididymal fat, brown fat), immunoblotting of uncoupling protein-1 (UCP1) protein in brown adipose tissue (BAT), and fasting plasma levels of glucose, insulin, glucagon-like peptide (GLP)-1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and leptin. RESULTS: Body weight increased postoperatively in both groups compared with preoperative weight, but it did not differ between the 2 groups. Eight weeks postoperatively, integrated blood glucose levels during the OGTT were decreased in IT compared with SH (P < .05). Fasting plasma levels of insulin, GLP-1, and GIP did not differ between the 2 groups, but PYY levels were higher in the IT animals (P < .01). The weight of epididymal and BATs, homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in the IT group (P < .05). Expression of UCP1 was higher in IT than SH animals (P < .05). CONCLUSION: These results suggest that IT improves glucose and lipid metabolism by decreasing insulin resistance and epididymal fat, and increased expression of UCP1 in BAT might be among the mechanisms responsible.


Subject(s)
Diabetes Mellitus/epidemiology , Diabetes Mellitus/metabolism , Glucose/metabolism , Ileum/surgery , Jejunum/surgery , Obesity/epidemiology , Obesity/metabolism , Adipose Tissue, Brown/metabolism , Animals , Body Weight/physiology , Comorbidity , Disease Models, Animal , Gastric Inhibitory Polypeptide/blood , Glucagon-Like Peptide 1/blood , Insulin Resistance/physiology , Ion Channels/metabolism , Leptin/blood , Lipid Metabolism/physiology , Male , Mitochondrial Proteins/metabolism , Peptide YY/blood , Rats, Inbred OLETF , Uncoupling Protein 1
8.
Surgery ; 151(5): 745-55, 2012 May.
Article in English | MEDLINE | ID: mdl-22244177

ABSTRACT

BACKGROUND: Parenteral nutrition (PN) is indispensable for meeting caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition; however, PN impairs hepatic immunity. We examined the effects of ω-3 and -6 polyunsaturated fatty acids, added individually to fat-free PN, on hepatic immunity in a murine model. We focused on serum liver enzymes, cytokine production, histopathology, and the outcomes after intraportal bacterial challenge. METHODS: Male Institute of Cancer Research mice were randomized into 4 groups; ad libitum chow (CHOW), fat-free PN (FF-PN), PN + fish oil (FO-PN), or PN + safflower oil (SO-PN). After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. The number of MNCs was counted and cytokine production (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by hepatic MNCs in response to lipopolysaccharide (LPS) was measured. Blood samples were analyzed for hepatobiliary biochemical parameters. Moreover, 1.0 × 10(7) pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined. RESULTS: Hepatic MNC numbers were significantly less in the FO-PN and FF-PN than in the CHOW group, whereas the SO-PN group showed moderate recovery of hepatic MNC numbers. The CHOW, FO-PN, and SO-PN groups showed LPS dose-dependent increases in TNF-α levels. These increases were blunted in the FF-PN group. IL-10 levels were increased LPS dose-dependently in the CHOW and FO-PN groups, but no marked changes were observed with LPS stimulation in the SO-PN and FF-PN groups. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly greater in the FF-PN than in the FO- and SO-PN and CHOW groups. The FO-PN group showed significantly improved survival compared with the SO-PN and FF-PN groups, showing essentially no morphologic hepatic abnormalities. CONCLUSION: Addition of fish oil to PN was advantageous in terms of reversing PN-induced deterioration of hepatic immunity, as reflected by altered cytokine production. Fish oil administration was also useful for preventing PN-induced hepatobiliary dysfunction. These changes seem to result in better survival and to protect against severe tissue damage after intraportal bacterial challenge. This therapy may have the potential to ameliorate PN-induced impairment of host immunity and thereby decrease morbidity and mortality.


Subject(s)
Fatty Acids, Omega-3/immunology , Fatty Acids, Omega-6/immunology , Fish Oils/immunology , Leukocytes, Mononuclear/metabolism , Liver/immunology , Parenteral Nutrition/methods , Safflower Oil/immunology , Animals , Biomarkers/metabolism , Cytokines/metabolism , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6/administration & dosage , Fish Oils/administration & dosage , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Liver/cytology , Liver/microbiology , Liver/pathology , Male , Mice , Mice, Inbred ICR , Parenteral Nutrition/adverse effects , Pseudomonas Infections/immunology , Pseudomonas Infections/prevention & control , Pseudomonas aeruginosa/immunology , Random Allocation , Safflower Oil/administration & dosage
9.
Hepatogastroenterology ; 58(105): 36-41, 2011.
Article in English | MEDLINE | ID: mdl-21510283

ABSTRACT

BACKGROUND/AIMS: Our aim was to study the effect of the viscosity of enteral nutrient solutions on upper gut motility and gut hormone secretion. METHODOLOGY: We used 5 beagle dogs equipped with strain gauge force transducers to measure upper gastrointestinal motility. Upper gut motility and gut hormone secretion were compared across 6 experimental conditions; control (oral solid meal), liquid-120, liquid-5 (liquid enteral nutrients administered for 120 and 5 min, respectively), low, middle, and high viscosity conditions. RESULTS: The magnitude of receptive relaxation was decreased in the liquid-120 compared to control, but this decrease was reversed with the increase of viscosity. The duration of the postprandial contractions in the proximal jejunum was decreased in the liquid-5 compared to the control, but this decrease was reversed in the middle and high viscosity conditions (p < 0.05). Rapid increase in plasma concentrations of gastric inhibitory polypeptide observed in the liquid-5 compared to the control was reversed in the low, middle, and high viscosity conditions. CONCLUSIONS: Although patterns of upper gut motility and gut hormone secretion after liquid enteral nutrients were considerably altered compared to those after solid meal ingestion, increasing the viscosity of liquid enteral nutrients reversed those altered patterns.


Subject(s)
Enteral Nutrition , Gastrointestinal Hormones/metabolism , Gastrointestinal Motility , Animals , Dogs , Gastric Inhibitory Polypeptide/metabolism , Transducers , Viscosity
10.
Gan To Kagaku Ryoho ; 37(5): 891-4, 2010 May.
Article in Japanese | MEDLINE | ID: mdl-20495322

ABSTRACT

A 75-year-old male who with type 3 gastric cardia cancer with multiple liver metastases was initially treated with S-1 in July of 2005. After 4 courses of the treatment, the liver metastases became undetectable on abdominal CT scan, with reduction in size of the primary tumor of the stomach. After 7 months of S-1 treatment, however, the progression of the primary lesion was endoscopically detected, and irinotecan was administered, demonstrating primary tumor regression. When re-growth of the primary tumor was observed, 3 courses of paclitaxel treatment showed little effect and was replaced by docetaxel treatment for 5 months, which had a grade 3 adverse effect. The next 10 courses of 5-FU combined with methotrexate were applied for one year until the primary tumor showed enlargement. Then 12 courses of CDDP with S-1 were administered until now, and the size of the primary carcinoma is under control. The patient is being followed on an outpatient basis without any surgical treatment, while the liver metastases have not relapsed on abdominal imaging.


Subject(s)
Antineoplastic Agents/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Aged , Gastroscopy , Humans , Liver Neoplasms/diagnostic imaging , Male , Neoplasm Staging , Quality of Life , Stomach Neoplasms/diagnostic imaging , Time Factors , Tomography, X-Ray Computed
11.
Surgery ; 148(5): 1012-9, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20417947

ABSTRACT

BACKGROUND: The aim of the present study was to investigate the effects of diversion of biliary and pancreatic juices on upper gut motility and hormone secretion. METHODS: We used dogs equipped with strain gauge force transducers to measure upper gut motility. Dogs were divided into 5 groups: control, sham operation, biliary diversion (BD), pancreatic juice diversion (PJD), and biliopancreatic juice diversion (BPD). Postprandial plasma concentrations of insulin, gastric inhibitory polypeptide (GIP), and peptide YY (PYY) were also measured. RESULTS: Occurrence and migration velocity of the migrating motor complex in the jejunum in the interdigestive state were decreased in the BD and BPD groups compared with the other 3 groups (P < .05). In the BD and BPD groups, areas of postprandial contractile curves in the upper gut were decreased, and the duration of the postprandial contractions in the proximal jejunum, which a previous study showed to correlate with gastric emptying, were less compared with the other 3 groups (P < .05). Plasma insulin levels did not differ among the 5 groups. Plasma concentrations of GIP suppressed in the PJD and BPD groups (P < .05), whereas plasma PYY level was increased in the BD group (P < .05). CONCLUSION: Bile diversion seems to inhibit interdigestive and postprandial upper gut contractions in association with an increase of plasma PYY. Pancreatic juice was considered to play a role in the secretion of GIP.


Subject(s)
Bile/physiology , Gastrointestinal Hormones/metabolism , Gastrointestinal Motility , Ileum/physiology , Pancreatic Juice/physiology , Animals , Blood Glucose/analysis , Dogs , Gastric Inhibitory Polypeptide/metabolism , Insulin/metabolism , Insulin Secretion , Peptide YY/metabolism
12.
J Trauma ; 65(2): 360-5; discussion 366, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18695472

ABSTRACT

BACKGROUND: Although parenteral nutrition (PN) prevents progressive malnutrition, lack of enteral nutrition (EN) during PN leads to gut associated lymphoid tissue (GALT) atrophy and dysfunction. Administering a small amount of EN with PN reportedly prevents increases in intestinal permeability. However, its effects on GALT remain unclear. We analyzed the minimum amount of EN required to preserve gut immunity during PN. METHODS: Male Institute of Cancer Research mice underwent jugular vein catheter insertion and tube gastrostomy. They were randomized into four groups to receive isocaloric and isonitrogenous nutritional support with variable EN to PN ratios (EN 0, EN 33, EN 66, and EN 100). EN was provided with a complex enteral diet. After 5 days of feeding, the mice were killed and whole small intestines were harvested. GALT lymphocytes were isolated and counted. Their phenotypes were analyzed by flow cytometry. IgA levels of small intestinal washings were analyzed with enzyme-linked immunosorbent assay. RESULTS: Body weight changes did not differ between any two of the groups. Peyer's patch lymphocyte numbers increased in proportion to EN amount, whereas lamina propria lymphocyte numbers were significantly higher in the EN 100 than in the EN 0 group, with no marked increases in the EN 33 and EN 66 groups. Small intestinal IgA levels increased EN amount-dependently and reached a plateau at EN 66. CONCLUSIONS: A small amount of EN partially reverses PN-induced GALT changes, suggesting beneficial but limited effects on gut mucosal immunity.


Subject(s)
Enteral Nutrition , Immunity, Mucosal/physiology , Intestinal Mucosa/immunology , Lymphoid Tissue/immunology , Parenteral Nutrition/adverse effects , Animals , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunoglobulin A/analysis , Lymphocyte Count , Male , Mice , Mice, Inbred ICR , Mucous Membrane/cytology , Peyer's Patches/cytology
13.
JPEN J Parenter Enteral Nutr ; 31(5): 416-22, 2007.
Article in English | MEDLINE | ID: mdl-17712151

ABSTRACT

BACKGROUND: Lack of enteral nutrition reduces gut-associated lymphoid tissue (GALT) mass and function, a mechanism underlying the increased morbidity of infectious complications in severely injured or critically ill patients. Strategies to restore parenteral nutrition (PN)-induced changes of GALT mass and function have been pursued. However, the influences of adding fish oil to PN on gut immunity remain to be clarified. METHODS: Male Institute of Cancer Research (ICR) mice (n = 50) were randomized to 4 groups: ad libitum chow (chow), fat free PN (fat (-)-PN), PN + fish oil (FO-PN), and PN + safflower oil (SO-PN). The PN groups were given isocaloric and isonitrogenous PN solutions. The FO- and SO-PN groups received 20% of total calories from fat emulsions. After 5 days of feeding, lymphocytes from Peyer's patches (PPs), the intraepithelial space (IE), and the lamina propria (LP) of the entire small intestine were isolated. GALT lymphocyte numbers and phenotypes (CD4+, CD8+, alphabetaTCR+, gammadeltaTCR+, B220+ cells) were determined. Immunoglobulin A (IgA) levels of small intestinal washings were also measured by enzyme-linked immunosorbent assay. Another set of mice (n = 24) was used to determine plasma fatty acid compositions after feeding. RESULTS: Lymphocyte numbers from PPs and the LP and intestinal IgA levels were significantly lower in the PN groups than in the chow group, with no significant differences between any 2 PN groups. The FO- and SO-PN groups showed moderate recovery of IE cell numbers compared with the fat (-)-PN group. Omega-3 and omega-6 fatty acid levels were increased with fish and safflower oil additions, respectively, compared with the fat (-)-PN group. CONCLUSIONS: Adding fish oil to PN does not exacerbate PN-induced GALT changes but rather partially reverses these changes, with increased plasma omega-3 fatty acid levels.


Subject(s)
Fish Oils/pharmacology , Intestine, Small/immunology , Lymphocyte Count , Lymphoid Tissue/drug effects , Parenteral Nutrition/methods , Peyer's Patches/immunology , Animals , Critical Illness , Fatty Acids, Unsaturated/analysis , Fatty Acids, Unsaturated/metabolism , Humans , Immunoglobulin A/analysis , Immunoglobulin A/immunology , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestine, Small/drug effects , Lymphoid Tissue/physiology , Male , Mice , Mice, Inbred ICR , Organ Size , Peyer's Patches/cytology , Peyer's Patches/drug effects , Random Allocation , Safflower Oil/pharmacology
14.
Ann Surg ; 245(4): 642-50, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17414615

ABSTRACT

OBJECTIVE: To clarify the influence of nutritional route on hepatic immunity in a murine model. SUMMARY BACKGROUND DATA: Parenteral nutrition is disadvantageous for preventing infectious complications in critically ill and/or severely injured patients as compared with enteral nutrition. To date, lack of enteral nutrition has been demonstrated to impair mucosal immunity, gut barrier function, and the peritoneal defense system. However, influences of nutritional route on hepatic immunity, another important defense system against infection, have not been well studied. METHODS: Male ICR mice were randomized to 3 groups: ad libitum chow (chow), intravenous (IV)-TPN and intragastric (IG)-TPN groups. The TPN groups were given isocaloric and isonitrogenous TPN solutions. After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. Hepatic MNC numbers and functions (cytokine production, intracellular signaling, and LPS receptor expression) were determined. Moreover, 1.0 x 10 Pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined. RESULTS: Hepatic MNC numbers were significantly lower in the IV-TPN group than in the chow and IG-TPN groups, without subpopulation changes. As compared with enterally fed mice, cytokine production (TNF-alpha, IFN-gamma, and IL-10) by hepatic MNCs in response to LPS was impaired in parenterally fed mice in association with blunted phosphorylation of ERK1/2, a MAPK. Hepatic MNCs from IV-TPN mice showed decreased expressions of CD14 and TLR4/MD2, as compared with enterally fed mice. Survival times were reduced in the IV-TPN group as compared with the chow and IG-TPN groups. CONCLUSION: Preservation of hepatic immunity with enteral feeding is important for prevention of infectious complications in severely injured and/or critically ill patients.


Subject(s)
Critical Illness , Cytokines/metabolism , Liver/immunology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Sepsis/immunology , Animals , Enteral Nutrition , Kupffer Cells/physiology , Lipopolysaccharide Receptors/metabolism , Liver/cytology , Male , Mice , Mice, Inbred ICR , Nutritional Support , Parenteral Nutrition, Total , Phosphorylation
15.
JPEN J Parenter Enteral Nutr ; 30(5): 388-93; discussion 393-4, 2006.
Article in English | MEDLINE | ID: mdl-16931606

ABSTRACT

BACKGROUND: Without enteral nutrition, the mass and function of gut-associated lymphoid tissue (GALT), a center of systemic mucosal immunity, are reduced. Therefore, new therapeutic methods, designed to preserve mucosal immunity during parenteral nutrition (PN), are needed. Our recent study revealed that exogenous interleukin-7 (IL-7; 1 microg/kg twice a day) restores the GALT cell mass lost during intravenous (IV) PN but does not improve secretory immunoglobulin A (IgA) levels. Herein, we studied the IL-7 dose response to determine the optimal IL-7 dose for recovery of GALT mass and function during IV PN. We hypothesized that a high dose of IL-7 would increase intestinal IgA levels, as well as GALT cell numbers. METHODS: Male mice (n = 42) were randomized to chow, IL-7-0, IL-7-0.1, IL-7-0.33, IL-7-1 and IL-7-3.3 groups and underwent jugular vein catheter insertion. The IL-7 groups were fed a standard PN solution and received IV injections of normal saline (IL-7-0), 0.1, 0.33, 1, or 3.3 microg/kg of IL-7 twice a day. The chow group was fed chow ad libitum. After 5 days of treatment, the entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). The lymphocytes were counted and phenotypes determined by flow cytometry (alphabetaTCR, gammadeltaTCR, CD4, CD8, B cell). IgA levels of small intestinal washings were also examined using ELISA (enzyme-linked immunoabsorbent assay). RESULTS: IL-7 dose-dependently increased total lymphocyte numbers in PPs and the LP. The number of lymphocytes harvested from IE spaces reached a plateau at 1 microg/kg of IL-7. There were no significant differences in any phenotype percentages at any GALT sites among the groups. IgA levels of intestinal washings were significantly higher in the chow group than in any of the IL-7 groups, with similar levels in all IL-7 groups. CONCLUSIONS: Exogenous IL-7 dose-dependently reverses PN-induced GALT cell loss, with no major changes in small intestinal IgA levels. IL-7 treatment during PN appears to have beneficial effects on gut immunity, but other therapeutic methods are needed to restore secretory IgA levels.


Subject(s)
Immunoglobulin A, Secretory/immunology , Interleukin-7/pharmacology , Intestine, Small/cytology , Intestine, Small/immunology , Lymphocyte Count , Animals , Dose-Response Relationship, Drug , Flow Cytometry , Injections, Intravenous , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Lymphoid Tissue , Male , Mice , Mice, Inbred ICR , Parenteral Nutrition , Peyer's Patches/cytology , Random Allocation , Specific Pathogen-Free Organisms , T-Lymphocytes/immunology
16.
JPEN J Parenter Enteral Nutr ; 30(5): 380-6; discussion 386-7, 2006.
Article in English | MEDLINE | ID: mdl-16931605

ABSTRACT

BACKGROUND: Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. METHODS: Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. RESULTS: On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. CONCLUSIONS: Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.


Subject(s)
Albumins/pharmacology , Intestinal Mucosa/drug effects , Intestine, Small/drug effects , Lymphocyte Count , Lymphoid Tissue/pathology , Reperfusion Injury/prevention & control , Animals , Disease Models, Animal , Flow Cytometry , Infusions, Intravenous , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestine, Small/blood supply , Intestine, Small/cytology , Intestine, Small/pathology , Lymphoid Tissue/immunology , Male , Mice , Mice, Inbred ICR , Parenteral Nutrition, Total , Peyer's Patches/immunology , Peyer's Patches/pathology , Phenotype , Postoperative Complications/epidemiology , Postoperative Complications/immunology , Random Allocation , Reperfusion Injury/immunology
17.
JPEN J Parenter Enteral Nutr ; 30(5): 395-8; discussion 399, 2006.
Article in English | MEDLINE | ID: mdl-16931607

ABSTRACT

BACKGROUND: Long-term antibiotic administration is sometimes necessary to control bacterial infections during the perioperative period. However, antibiotic administration may alter gut bacterial flora, possibly impairing gut mucosal immunity. We hypothesized that 1 week of subcutaneous (SC) antibiotic injections would affect Peyer's patch (PP) lymphocyte numbers and phenotypes, as well as mucosal immunoglobulin A (IgA) levels. METHODS: Sixty-one male Institute of Cancer Research mice were randomized to CMZ (cefmetazole 100 mg/kg, administered SC twice a day), IPM (imipenem/cilastatin 50 mg/kg x 2), and control (saline 0.1 mL x 2) groups. After 7 days of treatment, the mice were killed and their small intestines removed. Bacterial numbers in the small intestine were determined using sheep blood agar plates under aerobic conditions (n = 21). PP lymphocytes were isolated to determine cell numbers and phenotypes (CD4, CD8, alphabetaTCR, gammadeltaTCR, B220; n = 40). IgA levels in the small intestinal and bronchoalveolar washings were also measured with ELISA. RESULTS: Antibiotic administration decreased both bacterial number and the PP cell yield compared with the control group. There were no significant differences in either phenotype percentages or IgA levels at any mucosal sites among the 3 groups. CONCLUSIONS: Long-term antibiotic treatment reduces PP cell numbers while decreasing bacterial numbers in the small intestine. It may be important to recognize changes in gut mucosal immunity during long-term antibiotic administration.


Subject(s)
Anti-Bacterial Agents/pharmacology , Immunity, Mucosal , Immunoglobulin A, Secretory/drug effects , Peyer's Patches/immunology , Animals , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Enzyme-Linked Immunosorbent Assay/methods , Flow Cytometry , Immunity, Mucosal/drug effects , Immunoglobulin A, Secretory/isolation & purification , Intestine, Small/immunology , Intestine, Small/microbiology , Lymphocyte Count , Lymphocytes/classification , Lymphoid Tissue/cytology , Lymphoid Tissue/drug effects , Lymphoid Tissue/immunology , Male , Mice , Mice, Inbred ICR , Peyer's Patches/cytology , Phenotype , Random Allocation
18.
Shock ; 24(6): 541-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16317385

ABSTRACT

In the absence of enteral nutrient delivery, gut-associated lymphoid tissue (GALT) mass and function are reduced. The purpose of this study was to examine whether exogenous interleukin (IL)-7 treatment reverses intravenous (IV)-total parenteral nutrition (TPN)-induced changes in GALT, immunoglobulin (Ig) A levels, and gut barrier function. Eighty-nine mice were randomized to chow, TPN, or TPN + IL-7 (1 microg/kg, administered IV twice a day) and treated for 5 days. The entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). Small intestinal and bronchoalveolar IgA levels were measured. Proximal and distal small intestinal levels of IgA-stimulating (IL-10) and IgA-inhibiting (IFNgamma) cytokines were determined with enzyme-linked immunoabsorbant assay. Moreover, 1 x 10 live Pseudomonas aeruginosa were delivered by gavage and survival was observed. TPN decreased total cell yields from PPs, IE spaces, and the LP compared with the chow group. IL-7 treatment restored cell numbers. PP CD4+, PP CD8+, IE gammadeltaTCR+, and LP CD4+ cell numbers were higher in the TPN + IL-7 group than in the TPN group. Secretory IgA levels were lower in the TPN and TPN + IL-7 than in the chow group. In the distal small intestine, IFNgamma levels were similar in the three groups, whereas IL-10 levels were reduced in the TPN and TPN + IL-7 groups relative to the chow group. Survival times were reduced in the TPN compared with the chow group, but IL-7 treatment significantly improved survival. Thus, exogenous IL-7 does not improve secretory IgA levels, nor are there any remarkable effects on levels of gut IgA-mediating cytokines. However, IL-7 treatment during TPN reverses TPN-induced GALT atrophy and improves survival in a gut-derived sepsis model.


Subject(s)
Interleukin-7/administration & dosage , Parenteral Nutrition, Total , Peyer's Patches/immunology , Animals , Immunoglobulin A, Secretory/immunology , Interleukin-7/immunology , Intestinal Mucosa , Intestine, Small/immunology , Male , Mice , Pseudomonas Infections/immunology , Sepsis/immunology , Specific Pathogen-Free Organisms , T-Lymphocytes/immunology
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