Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

PubMed

Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

2014-08-01

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

PubMed

Rittler, Peter; Schiefer, Beatrice; Demmelmair, Hans; Koletzko, Berthold; Vogeser, Michael; Alpers, David H; Jauch, Karl-Walter; Hartl, Wolfgang H

2006-01-01

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the

Intestinal manipulation affects mucosal antimicrobial defense in a mouse model of postoperative ileus

PubMed Central

Hieggelke, Lena; Schneiker, Bianca; Lysson, Mariola; Stoffels, Burkhard; Nuding, Sabine; Wehkamp, Jan; Kikhney, Judith; Moter, Annette; Kalff, Joerg C.

2018-01-01

Aim To explore the effects of abdominal surgery and interleukin-1 signaling on antimicrobial defense in a model of postoperative ileus. Methods C57BL/6 and Interleukin-1 receptor type I (IL-1R1) deficient mice underwent intestinal manipulation to induce POI. Expression of mucosal IL-1α, IL-1β and IL-1R1 and several antimicrobial peptides and enzymes were measured by quantitative PCR or ELISA, western blotting or immunohistochemistry. Bacterial overgrowth was determined by fluorescent in-situ hybridization and counting of jejunal luminal bacteria. Translocation of aerobic and anaerobic bacteria into the intestinal wall, mesenteric lymph nodes, liver and spleen was determined by counting bacterial colonies on agar plates 48h after plating of tissue homogenates. Antimicrobial activity against E. coli and B. vulgatus was analyzed in total and cationic fractions of small bowel mucosal tissue homogenates by a flow cytometry-based bacterial depolarization assay. Results Jejunal bacterial overgrowth was detected 24h after surgery. At the same time point, but not in the early phase 3h after surgery, bacterial translocation into the liver and mesenteric lymph nodes was observed. Increased antimicrobial activity against E. coli was induced within early phase of POI. Basal antimicrobial peptide and enzyme gene expression was higher in the ileal compared to the jejunal mucosa. The expression of lysozyme 1, cryptdin 1, cryptdin 4 and mucin 2 were reduced 24h after surgery in the ileal mucosa and mucin 2 was also reduced in the jejunum. Postoperative IL-1α and IL-1β were increased in the postoperative mucosa. Deficiency of IL-1R1 affected the expression of antimicrobial peptides during homeostasis and POI. Conclusion Small bowel antimicrobial capacity is disturbed during POI which is accompanied by bacterial overgrowth and translocation. IL-1R1 is partially involved in the gene expression of mucosal antimicrobial peptides. Altered small bowel antimicrobial activity may

Ileal brake activation: macronutrient-specific effects on eating behavior?

PubMed

van Avesaat, M; Troost, F J; Ripken, D; Hendriks, H F; Masclee, A A M

2015-02-01

Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown. The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control. This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4 kg m(-2)) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7 kcal), low-dose casein ((LP) 17.2 kcal) or high-dose casein ((HP) 51.7 kcal), low-dose sucrose ((LC) 17.2 kcal) and high-dose sucrose ((HC) 51.7 kcal), over a period of 90 min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals. Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7 kcal, P<0.001; HP: 458.0±78.6 kcal, P<0.005; HC: 399.0±57.0 kcal, P<0.0001 vs control: 586.7±70.2 kcal, P<0.001, respectively). A reduction in energy intake was still apparent when the caloric amount of infused nutrients was added to the amount eaten during the ad libitum meal.Secretion of cholecystokinin and peptide YY but not of glucagon-like peptide-1 (7-36) was increased during ileal perfusion of fat, carbohydrates and protein. During ileal perfusion of all macronutrients, a delay in gastric emptying and intestinal transit was observed, but differences were not significant compared with control. Apart from lipids, also

Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

PubMed Central

Whittaker, Alexandra L; Zhu, Ying; Howarth, Gordon S; Loung, Chi S; Bastian, Susan E P; Wirthensohn, Michelle G

2017-01-01

AIM To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical, histological and behavioural markers. METHODS Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy. Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms. This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats. Female Dark Agouti rats were gavaged (days 3-11) with either PBS, almond hull or almond blanched water extract at two doses, and were injected intraperitoneally with 5-fluorouracil (5-FU-150 mg/kg) or saline on day 9 to induce mucositis. Burrowing behavior, histological parameters and myeloperoxidase activity were assessed. RESULTS Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls (P < 0.05). Rats administered 5-FU significantly increased jejunal and ileal MPO levels (1048%; P < 0.001 and 409%; P < 0.001), compared to healthy controls. Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone (rise 50%, 1088 ± 96 U/g vs 723 ± 135 U/g, P = 0.02). Other extract-related effects on inflammatory activity were minimal. 5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis (median of 9.75 vs 0; P < 0.001). The extracts had no ameliorating effect on histological severity score in the jejunum or ileum. Burrowing behavior was significantly reduced in all chemotherapy-treated groups (P = 0.001). The extracts failed to normalize burrowing activity to baseline levels. CONCLUSION Almond extracts at these dosages offer little beneficial effect on mucositis

VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation.

PubMed

Soo, I; Madsen, K L; Tejpar, Q; Sydora, B C; Sherbaniuk, R; Cinque, B; Di Marzio, L; Cifone, M Grazia; Desimone, C; Fedorak, R N

2008-03-01

Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase. To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis. Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (10(9) colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment. Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (+/- SEM) ulcerative colitis disease activity index scores from 5.3+/-1.8946 to 0.70+/-0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity. Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity.

The influence of copper concentration and source on ileal microbiota.

PubMed

Pang, Y; Patterson, J A; Applegate, T J

2009-03-01

Copper is normally supplemented in poultry diets as a growth promotant and antimicrobial. However, there are conflicting reports about the growth benefits and little information about how Cu affects the microbiota in the intestinal tract of poultry. Therefore, in vitro and in vivo experiments were conducted with broilers to determine the effects of Cu source and supplementation on ileal microbiota. The influence of Cu on growth of lactobacilli and Escherichia coli in media inoculated with ileal contents was determined in the first study. When Cu sulfate pentahydrate was supplemented to the cultures, quadratic increases in lactobacilli to graded concentrations of Cu up to 125 mg/kg and quadratic decreases in E. coli up to 250 mg/kg of Cu were observed after 24 h of incubation at 37 degrees C. However, when tribasic Cu chloride (TBCC) was supplemented, neither linear nor quadratic responses to graded concentrations of dietary Cu were observed on number of lactobacilli or number of E. coli. The effects of Cu and Cu source on ileal microbiota and growth performance in broiler chickens were determined in the second study. Bird performance was not affected by Cu source or concentration. The bacterial culture enumeration results revealed that supplementation with 187.5 mg/kg of Cu from Cu sulfate pentahydrate and TBCC had no effect on number of ileal lactobacilli of birds. The denaturing gradient gel electrophoresis analyses of ileal microbial communities revealed that neither Cu supplementation nor source had effects on the number of bacterial species predominant in the ileal digesta or associated with the ileal mucosa. Supplementation with TBCC supplementation significantly increased the similarity coefficients of microbiota in the ileal mucosa compared with cross-products of all individuals. This suggests that TBCC may alter the intestinal microbiota, yet this shift had no effect on bird performance.

SeHCAT absorption: a simple test of ileal dysfunction.

PubMed

Fagan, E A; Chadwick, V S; Baird, I M

1983-01-01

A new selenium-labelled synthetic bile salt SeHCAT (taurine conjugate of 23-[75Se]-25-homocholic acid) was assessed as a test of ileal dysfunction in 20 patients with inflammatory bowel disease (IBD). Whole body retention of SeHCAT was compared with tests of vitamin B12 absorption (Schilling test and whole body retention) and the cholylglycine-1-14C breath test and faecal isotope excretion. Clear differentiation, with no overlap was obtained between 10 normal subjects and patients with ileal disease/resection in the SeHCAT 7-day retention results. The Schilling test was more sensitive; enabling discrimination between patients with limited and extensive ileal disease/resection. An unexpected rise in SeHCAT retention was observed in patients with colonic IBD. The 7-day SeHCAT retention is a safe, simple screening test for ileal dysfunction and has practical advantages compared with the Schilling test.

Case report of primary intestinal lymphangiectasia diagnosed in an octogenarian by ileal intubation and by push enteroscopy after missed diagnosis by standard colonoscopy and EGD

PubMed Central

Cappell, Mitchell S.; Edhi, Ahmed; Amin, Mitual

2018-01-01

Abstract Rationale: Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation. Diagnoses: A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia. Interventions/Outcomes: Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein

Under pressure: a contribution to the pathogenesis of acquired ileal atresia

PubMed Central

Houben, C H; Lo, A W I; Tsui, S Y; Chan, K W

2013-01-01

An acquired ileal atresia is a rare occurrence. A 3-week-old neonate is presented, who developed postnatally a type 2 ileal atresia and an ileal stenosis within a pre-existing internal hernia secondary to an adhesion band. The literature reports a total of eight cases (4 females) with acquired ileal atresia in babies ranging in age from 3 weeks to 2 years (median 4 months). Mechanical forces (eg, adhesion band, intussusception and volvulus) onto the intestine are most frequently (75%) implicated as the primary event. The distal ileum is most often affected and a type 3A atresia is identified in six of eight (75%) cases. PMID:24225736

Inclusion of dietary β-mannanase improves performance and ileal digestibility and reduces ileal digesta viscosity of broilers fed corn-soybean meal based diet.

PubMed

Balasubramanian, B; Ingale, S L; Park, J Hong; Rathi, P C; Shanmugam, S; Kim, I H

2018-05-16

This study was aimed to evaluate the influence of dietary β-mannanase inclusion on growth performance, apparent ileal digestibility, digesta viscosity, blood metabolites and excreta noxious gas emissions in broilers fed corn-soybean meal based diet. A total of 600 conventional healthy 1-d-old ROSS 308 broilers with body weight 45 ± 0.50 g (mean ± SD) were randomly assigned to 4 dietary treatments with 10 replicates cages, with 15 broilers in each and fed basal diet supplemented to corn-SBM based diets with 0, 2400, 4800, and 7200 MNU β-mannanase/kg for 35 d feeding trial period. Significant results were observed on improved average daily gain and reduced feed conversion ratio during trial period and also reduced ileal digesta viscosity and improved apparent ileal digestibility of dry matter, nitrogen and energy. However, no significant effects were found on blood urea nitrogen and creatinine, excreta noxious gas emissions. In conclusion, the inclusion of dietary β-mannanase had potential to improve daily gain and feed efficiency and apparent ileal digestibility while decreasing digesta viscosity of broiler.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.

PubMed

Moeser, Adam-J; Nighot, Prashant-K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony-T

2008-10-21

To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin. This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.

⁶⁸Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors.

PubMed

Calissendorff, Jan; Sundin, Anders; Falhammar, Henrik

2014-09-01

Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by (68)Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All (68)Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients' activity of daily life. (68)Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of (68)Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.

Luminally-polarized mural and vascular remodeling in ileal strictures of Crohn's Disease.

PubMed

Zhang, Xiaofei; Ko, Huaibin Mabel; Torres, Joana; Panchal, Hinaben J; Cai, Zhenjian; Wagner, Mathilde; Sands, Bruce E; Colombel, Jean-Frederic; Cho, Judy; Taouli, Bachir; Harpaz, Noam

2018-03-16

Intestinal stricture, a major complication of Crohn's disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histological sections from 37 surgically-resected ileal strictures and adjacent non-strictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red) and collagen types I, III and V. Overall mural thickening in strictures was increased 2.4±0.3-fold compared with non-strictured regions of the same specimens. The muscular layer most altered was the muscularis mucosae (MM). Compared with the inner and outer layers of the MP which were expanded 2.1±0.2- and 1.4±0.1-fold, respectively, the MM was expanded 22.1±3.6-fold, reflecting the combined effects of architectural disarray, an 11.6±1.4-fold increase smooth muscle content, and elaboration of pericellular type V collagen. In contrast, the architecture of the MP was preserved and pericellular collagen was virtually absent; rather, fibrosis in this layer was limited to expansion of the intramuscular septa by collagen types I and III. The muscular arteries and veins within the strictured submucosa frequently exhibited eccentric, luminally-oriented adventitial mantles comprising hyperplastic myocytes and extracellular type V collagen. We conclude that the fibromuscular remodeling which results in CD-associated ileal strictures predominantly involves the MM and submucosal vasculature in a luminally-polarized fashion and suggests that mucosal-based factors may contribute to stricture pathogenesis. Copyright © 2018. Published by Elsevier Inc.

Glutamine attenuates the inhibitory effect of methotrexate on TLR signaling during intestinal chemotherapy-induced mucositis in a rat

PubMed Central

2014-01-01

Toll-like receptor 4 (TLR-4) is crucial in maintaining intestinal epithelial homeostasis, participates in a vigorous signaling process and heightens inflammatory cytokine output. The objective of this study was to determine the effects of glutamine (GLN) on TLR-4 signaling in intestinal mucosa during methotrexate (MTX)-induced mucositis in a rat. Male Sprague–Dawley rats were randomly assigned to one of four experimental groups of 8 rats each: 1) control rats; 2) CONTR-GLN animals were treated with oral glutamine given in drinking water (2%) 48 hours before and 72 hours following vehicle injection; 3) MTX-rats were treated with a single IP injection of MTX (20 mg/kg); and 4) MTX-GLN rats were pre-treated with oral glutamine similar to group B, 48 hours before and 72 hours after MTX injection. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. The expression of TLR-4, MyD88 and TRAF6 in the intestinal mucosa was determined using real time PCR, Western blot and immunohistochemistry. MTX-GLN rats demonstrated a greater jejunal and ileal mucosal weight and mucosal DNA, greater villus height in ileum and crypt depth and index of proliferation in jejunum and ileum, compared to MTX animals. The expression of TLR-4 and MyD88 mRNA and protein in the mucosa was significantly lower in MTX rats versus controls animals. The administration of GLN increased significantly the expression of TLR-4 and MyD88 (vs the MTX group). In conclusion, treatment with glutamine was associated with up-regulation of TLR-4 and MyD88 expression and a concomitant decrease in intestinal mucosal injury caused by MTX-induced mucositis in a rat. PMID:24742067

Case report of primary intestinal lymphangiectasia diagnosed in an octogenarian by ileal intubation and by push enteroscopy after missed diagnosis by standard colonoscopy and EGD.

PubMed

Cappell, Mitchell S; Edhi, Ahmed; Amin, Mitual

2018-01-01

Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation. A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia. Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein diet, supplements of fat-soluble vitamins, and avoiding

True ileal amino acid digestibility and endogenous ileal amino acid losses in growing pigs fed wheat shorts- or casein-based diets.

PubMed

Libao-Mercado, A J; Yin, Y; van Eys, J; de Lange, C F M

2006-06-01

Use of dietary AA in growing pigs reflects digestion and use of digested AA for various body functions. Before evaluating dietary effects on use of digestible AA intake for body protein deposition, a digestibility study was conducted to investigate true ileal AA digestibility and endogenous ileal AA losses in growing pigs fed graded levels of wheat shorts (WS) or casein (CS; control). A casein-based basal diet (basal) was formulated to contain 0.27 g of standardized ileal digestible (SID) Lys per MJ of DE, to which extra Lys was added from WS (WS2, +0.10 g of SID Lys per MJ of DE; WS3, +0.20 g of SID Lys per MJ of DE) or casein (CS3, +0.20 g of SID Lys per MJ of DE). A fifth diet was formulated to be similar in CP level and source as CS3 but in which 6% pectin, a source of soluble non-starch polysaccharides (NSP), was included at the expense of cornstarch (CS3 + pectin). Five Yorkshire barrows (17.5 +/- 1.5 kg of BW) were fitted with a T-cannula at the distal ileum and randomly assigned to 1 of the 5 experimental diets in a 5 x 5 Latin Square design. Apparent ileal digestibility (AID), true ileal digestibility (TID), and endogenous ileal protein losses (EPL) were determined using the homoarginine method. Diet CS level did not influence (P > or = 0.10) TID of most essential AA or EPL (10.4 g/kg of DM intake). Including pectin in the diet did not influence TID of AA (P > or = 0.10) but increased EPL (15.6 g/kg of DM intake; P > or = 0.01). Inclusion of WS in the diet reduced TID of most essential AA (P < 0.01). The TID values for most essential AA, however, were the same (P > or = 0.10) for both dietary WS levels, except for Lys and Met, which were further reduced at the greatest dietary WS level. Increased EPL (P < 0.01) was only observed for WS3 (16 g/kg of DMI). We concluded that (1) the effects of dietary protein source on AID of AA can be attributed both to reduced TID of AA and increased EPL, (2) the impact of dietary WS level on TID of AA and EPL does not seem

Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls.

PubMed

Kleessen, B; Kroesen, A J; Buhr, H J; Blaut, M

2002-09-01

Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls (P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria, the Enterobacteriaceae, the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

PubMed Central

Moeser, Adam J; Nighot, Prashant K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony T

2008-01-01

AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer’s solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1 μmol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of 3H-mannitol and 14C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier. PMID:18932279

Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

PubMed

Kim, Hyun Jin; Kim, Jin Hyun; Moon, Won; Park, Jongha; Park, Seun Ja; Song, Geun Am; Han, Seung Hee; Lee, Jong Hun

2015-01-01

5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-β1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-β1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock.

PubMed

Belmonte, Liliana; Coëffier, Moïse; Le Pessot, Florence; Miralles-Barrachina, Olga; Hiron, Martine; Leplingard, Antony; Lemeland, Jean-François; Hecketsweiler, Bernadette; Daveau, Maryvonne; Ducrotté, Philippe; Déchelotte, Pierre

2007-05-28

To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 +/- 1.05 vs 1.72 +/- 0.46 mumol/g tissue, P<0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal alpha1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

Is Health-Related Quality of Life after Radical Cystectomy Using Validated Questionnaires Really Better in Patients with Ileal Orthotopic Neobladder Compared to Ileal Conduit: A Meta-Analysis of Retrospective Comparative Studies

PubMed Central

Cerruto, Maria A.; D'Elia, Carolina; Siracusano, Salvatore; Porcaro, Antonio B.; Cacciamani, Giovanni; De Marchi, Davide; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Belgrano, Emanuele; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Rizzo, Michele; Visalli, Francesco; Verze, Paolo; Artibani, Walter

2017-01-01

Introduction From the most recent systematic revision of the literature, an orthotopic neobladder would seem to show marginally better health related quality of life (HR-QoL) scores compared with an ileal conduit. The aim of this study was to review all relevant published studies about the comparison between ileal orthotopic neobladder (IONB) and ileal conduit using validated HR-QoL questionnaires. Materials and Methods Studies were identified by searching multiple literature databases. Data were synthesized using meta-analytic methods conformed to the PRISMA statement. Results The literature search identified 10 papers; pooled effect sizes of combined quality of life outcomes for ileal conduit versus IONB showed a significantly better HR-QoL in patients with IONB (Hedges' g = 0.278; p = 0.000);. The present study has an important limitation due to the type of the analyzed comparative studies, all retrospective and not randomized. Conclusion This meta-analysis of not-randomized, retrospective comparative studies on the impact of ileal conduit versus IONB on HR-QoL showed a significant advantage of IONB subgroups. PMID:28785189

Is Health-Related Quality of Life after Radical Cystectomy Using Validated Questionnaires Really Better in Patients with Ileal Orthotopic Neobladder Compared to Ileal Conduit: A Meta-Analysis of Retrospective Comparative Studies.

PubMed

Cerruto, Maria A; D'Elia, Carolina; Siracusano, Salvatore; Porcaro, Antonio B; Cacciamani, Giovanni; De Marchi, Davide; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Belgrano, Emanuele; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Rizzo, Michele; Visalli, Francesco; Verze, Paolo; Artibani, Walter

2017-07-01

From the most recent systematic revision of the literature, an orthotopic neobladder would seem to show marginally better health related quality of life (HR-QoL) scores compared with an ileal conduit. The aim of this study was to review all relevant published studies about the comparison between ileal orthotopic neobladder (IONB) and ileal conduit using validated HR-QoL questionnaires. Studies were identified by searching multiple literature databases. Data were synthesized using meta-analytic methods conformed to the PRISMA statement. The literature search identified 10 papers; pooled effect sizes of combined quality of life outcomes for ileal conduit versus IONB showed a significantly better HR-QoL in patients with IONB (Hedges' g = 0.278; p = 0.000);. The present study has an important limitation due to the type of the analyzed comparative studies, all retrospective and not randomized. This meta-analysis of not-randomized, retrospective comparative studies on the impact of ileal conduit versus IONB on HR-QoL showed a significant advantage of IONB subgroups.

Quality of life after Brooke ileostomy and ileal pouch-anal anastomosis. Comparison of performance status.

PubMed Central

Pemberton, J H; Phillips, S F; Ready, R R; Zinsmeister, A R; Beahrs, O H

1989-01-01

Although the clinical results of Brooke ileostomy are good, patients are permanently incontinent of stool and gas. Alternative operations designed to restore enteric continence, such as ileal pouch-anal anastomosis, must not only be as safe and effective as Brooke ileostomy, but should provide an improved quality of life in order to establish long-term acceptability. Ileal pouch-anal anastomosis has been performed safely and good functional results have been reported. The quality of life after ileal pouch-anal anastomosis, however, has not been documented. Two hundred ninety-eight ileal pouch patients and 406 Brooke ileostomy patients who had the operations performed for chronic ulcerative colitis or familial adenomatous polyposis formed the basis of the study. After adjusting for age, diagnosis, and reoperation rate, logistic regression analysis of performance scores in seven different categories was used to discriminate between operations. Median follow-up was longer in Brooke ileostomy patients than in ileal pouch patients (104 months vs. 47 months, respectively), and Brooke ileostomy patients were slightly older (38 years vs. 32 years). A great majority of patients in each group were satisfied (93% Brooke ileostomy; 95% ileal pouch-anal anastomosis). Thirty-nine per cent of Brooke ileostomy patients, however, desired a change in the type of ileostomy they had. At 47 months, ileal pouch patients had a median of 5 stools per day and 1 at night, 77% did not experience any daytime incontinence, while 22% reported occasional spotting. In each performance category, the performance score discriminated between operations, with the probability of having had an ileal pouch-anal anastomosis operation increasing with improvement in performance scores (p less than 0.05). We concluded that after ileal pouch-anal anastomosis, patients experienced significant advantages in performing daily activities compared to patients with Brooke ileostomy and thus may experience a better

[Prevention of side effects and complications after operation for partial ileal bypass].

PubMed

Mirchuk, K K; Sedletskiĭ, Iu I

2014-01-01

Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.

A rare case of ileal metastasis from cervical cancer.

PubMed

Iliescu, L; David, L; Orban, C; Herlea, V; Toma, L

2014-01-01

We present the case of a 70-year-old woman, with a history of radiation-treated and surgically- resected cervical cancer, who was admitted to our clinic for intermittent sub occlusive symptoms. CT scan revealed a liver nodule and intestinal obstruction. The patient underwent surgery for excision of suspected liver metastasis and resolution of intestinal obstruction.Intraoperatively an ileal tumour was found to be the cause of the obstruction. Anatomo-pathological findings were consistent with an ileal metastasis from the cervical cancer.The liver nodule was only an area of focal steatosis. Celsius.

Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes.

PubMed

Deponte, Marcel

2013-05-01

Glutathione-dependent catalysis is a metabolic adaptation to chemical challenges encountered by all life forms. In the course of evolution, nature optimized numerous mechanisms to use glutathione as the most versatile nucleophile for the conversion of a plethora of sulfur-, oxygen- or carbon-containing electrophilic substances. This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms of glutathione-dependent enzymes, including glutathione reductase, glutaredoxins, glutathione peroxidases, peroxiredoxins, glyoxalases 1 and 2, glutathione transferases and MAPEG. Moreover, open mechanistic questions, evolutionary aspects and the physiological relevance of glutathione catalysis are discussed for each enzyme family. It is surprising how little is known about many glutathione-dependent enzymes, how often reaction geometries and acid-base catalysts are neglected, and how many mechanistic puzzles remain unsolved despite almost a century of research. On the one hand, several enzyme families with non-related protein folds recognize the glutathione moiety of their substrates. On the other hand, the thioredoxin fold is often used for glutathione catalysis. Ancient as well as recent structural changes of this fold did not only significantly alter the reaction mechanism, but also resulted in completely different protein functions. Glutathione-dependent enzymes are excellent study objects for structure-function relationships and molecular evolution. Notably, in times of systems biology, the outcome of models on glutathione metabolism and redox regulation is more than questionable as long as fundamental enzyme properties are neither studied nor understood. Furthermore, several of the presented mechanisms could have implications for drug development. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock

PubMed Central

Belmonte, Liliana; Coëffier, Moïse; Pessot, Florence Le; Miralles-Barrachina, Olga; Hiron, Martine; Leplingard, Antony; Lemeland, Jean-François; Hecketsweiler, Bernadette; Daveau, Maryvonne; Ducrotté, Philippe; Déchelotte, Pierre

2007-01-01

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model. PMID:17569119

[Effect of enteral supplement of arginine on intestinal adaptation and its mechanism in experimental rats with short bowel syndrome].

PubMed

Jiang, Xiao-hua; Li, Ning; Zhu, Wei-ming; Li, Jie-shou

2009-09-01

To evaluate the effect of enteral supplement of arginine on intestinal adaptation in rats with short bowel syndrome (SBS) and to study its mechanism. SD rats were randomly assigned to three groups: sham rats (Con), SBS rats (SB) and SBS rats supplemented with enteral arginine (SB-Arg). All the animals received isonitrogenic and isocaloric enteral nutrition, except that SB-Arg rats received enteral nutrition supplemented with arginine (300 mg kg(-1) d(-1)). Fat absorbability, plasma free fatty acids, parameters of intestinal adaptation, enterocytes proliferation and apoptosis were determined. After massive small bowel resection, rats had significant bowel adaptation. Compared with SB rats, SB-Arg rats demonstrated a significant increase in fat absorbability [(84.9+/-3.2)% vs [(81.3+/-3.9)%], plasma level of free fatty acids [(650.0+/-86.5) vs (289.5+/-76.9) mg/L], ileal mucosal weight [(18.0+/-3.5) vs (13.5+/-3.0) mg cm(-1) 100 g(-1)], ileal DNA content [(29.6+/-3.3) vs (26.0+/-2.6) microg cm(-1) 100 g(-1)], jejunal mucosal protein content [(65.5+/-7.3) vs (59.8+/-6.2) microg cm(-1) 100 g(-1)], ileal mucosal protein content[(39.2+/-2.3) vs(35.4+/-2.3) microg cm(-1) 100 g(-1)], jejunal mucosal proliferation index [31+/-4 vs 22+/-3] and ileal mucosal proliferation index [32+/-2 vs 25+/-3] (all P<0.05). Moreover, jejunal and ileal villus length, crypt depth and mucosal thickness in SBS-Arg rats were higher than those in SB rats (P<0.05). In rat SBS model, enteral supplement of arginine appears to stimulate intestinal structural and functional adaptation. The mechanism may be that arginine can stimulate enterocyte proliferation and inhibit enterocyte apoptosis.

Total intracorporeal robot-assisted laparoscopic ileal conduit (Bricker) urinary diversion: technique and outcomes.

PubMed

Rehman, Jamil; Sangalli, Mattia N; Guru, Khurshid; de Naeyer, Geert; Schatteman, Peter; Carpentier, Paul; Mottrie, Alexander

2011-02-01

Several recent preliminary reports have demonstrated that Robot-Assisted Cystectomy with total intracorporeal Ileal Conduit (RACIC) is a feasible option over the open technique. We report our stepwise surgical procedure of robotic total intracorporeal ileal conduit urinary diversion, technical consideration, development, refinements and initial experience. Only the ileal conduit urinary diversion is described with no emphasis on the cystectomy's steps. Between February 2008 and September 2009, nine patients underwent RACIC for muscle invasive transitional cell carcinoma (TCC). The entire procedure, including radical cystoprostatectomy, extended pelvic node dissection (ePLND), ileal conduit urinary diversion (Bricker) including isolation of the ileal loop (20 cm ileal segment) 15 cm away from the ileocecal junction, restoration of bowel continuity with stapled side-to-side ileo-ileal anastomosis, retroperitoneal transfer of the left ureter to the right side, and bilateral stented (8 F feeding tube) ileo-ureteral anastomoses in a Wallace faction were all performed exclusively intracorporeally using the da Vinci Si surgical robot and finally the conduit stoma was fashioned. The RACIC was technically successful in all nine patients (three females and six males. Mean age 74.1; 57 to 87) without open conversion. The mean operative time including extended pelvic lymphadenectomy and urinary diversion was 346.2 minutes (210 to 480). Mean operative time of diversion is 72 minutes (52-113) mean estimated blood loss 258 mL (200 to 500) and the median hospital stay were 14 days (10 to 27). In all three female patients, the specimen was extracted through the vagina. There were no intraoperative complications and only one major postoperative complication: one postoperative iatrogenous necrosis of the ileal conduit caused by uncareful retraction of the organ bag and thereby probably injuring the conduit pedicle, as the ileal conduit was well vascularised at the end of the

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

PubMed

Beiler, H A; Steinorth, J; Witt, A; Mier, W; Mohammed, A; Waag, K L; Zachariou, Z

2004-10-01

After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

PubMed

Jasek, A; Latham, R E; Mañón, A; Llamas-Moya, S; Adhikari, R; Poureslami, R; Lee, J T

2018-06-08

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing �

Improved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling.

PubMed

Greig, Chasen J; Cowles, Robert A

2017-07-01

Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used. 5-HT signaling is potentiated by targeting the serotonin reuptake transporter (SERT) molecule. Selective serotonin reuptake inhibitor-treated wild-type (WT-SSRI), SERT-knockout (SERTKO), and wild-type C57Bl/6 (WT) mice were used. Distal ileal sections were H&E-stained. Villus height (VH), width (VW), crypt width (CW), and bowel diameter were used to calculate surface area enlargement factor (SEF) and MSA. VH alone for SERTKO and SSRI was significantly increased compared to WT, without a difference between SERTKO and WT-SSRI. VW and CW were significantly decreased for both SERTKO and WT-SSRI compared to WT, and VW for WT-SSRI was also decreased compared to SERTKO. These changes increased SEF and MSA for SERTKO and WT-SSRI compared to WT. Additionally, SEF and MSA were significantly increased for WT-SSRI compared to SERTKO. Mathematical modeling provides a valuable tool for differentiating changes in intestinal MSA. This more comprehensive assessment of surface area does not appear to correlate linearly with standard morphometric measures and represents a more comprehensive method for discriminating between therapies aimed at increasing functional intestinal mucosa. © 2017 Wiley Periodicals, Inc.

Resuscitation With 100% Oxygen Causes Intestinal Glutathione Oxidation and Reoxygenation Injury in Asphyxiated Newborn Piglets

PubMed Central

Haase, Erika; Bigam, David L.; Nakonechny, Quentin B.; Jewell, Laurence D.; Korbutt, Gregory; Cheung, Po-Yin

2004-01-01

Objective: To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen. Summary Background Data: Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury. Methods: Newborn piglets subjected to severe hypoxemia for 2 hours were resuscitated with 21%, 50%, or 100% oxygen while superior mesenteric artery (SMA) flow and hemodynamic parameters were continuously measured. Small intestinal tissue samples were analyzed for histologic injury and levels of oxidized and reduced glutathione. Results: SMA blood flow decreased to 34% and mesenteric oxygen delivery decreased to 9% in hypoxemic piglets compared with sham-operated controls. With reoxygenation, SMA blood flow increased to 177%, 157%, and 145% of baseline values in piglets resuscitated with 21%, 50%, and 100% oxygen, respectively. Mesenteric oxygen delivery increased to more than 150% of baseline values in piglets resuscitated with 50% or 100% oxygen, and this correlated significantly with the degree of oxidative stress, as measured by the oxidized-to-reduced glutathione ratio. Two of eight piglets resuscitated with 100% oxygen developed gross and microscopic evidence of pneumatosis intestinalis and severe mucosal injury, while all other piglets were grossly normal. Conclusions: Resuscitation of hypoxemic newborn piglets with 100% oxygen is associated with an increase in oxygen delivery and oxidative stress, and may be associated with the development of small intestinal hypoxia-reoxygenation injury. Resuscitation of asphyxiated newborns with lower oxygen concentrations may help to decrease

Paradoxical Impact of Ileal Pouch-Anal Anastomosis on Male and Female Fertility in Patients With Ulcerative Colitis.

PubMed

Pachler, Frederik R; Brandsborg, Søren B; Laurberg, Søren

2017-06-01

Birth rates in males with ulcerative colitis and ileal pouch-anal anastomosis have not been studied. This study aimed to estimate birth rates in males and females with ulcerative colitis and study the impact of ileal pouch-anal anastomosis. This was a retrospective registry-based cohort study that was performed over a 30-year period. Records for parenting a child from the same period were cross-linked with patient records, and birth rates were calculated using 15 through 49 years as age limits. All data were prospectively registered. All patients with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis between 1980 and 2010 were identified in Danish national databases. The primary outcomes measured were birth rates in females and males with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis. We included 27,379 patients with ulcerative colitis (12,812 males and 14,567 females); 1544 had ileal pouch-anal anastomosis (792 males and 752 females). Patients with ulcerative colitis have slightly reduced birth rates (males at 40.8 children/1000 years, background population 43.2, females at 46.2 children/1000 years, background population 49.1). After ileal pouch-anal anastomosis, males had increased birth rates at 47.8 children/1000 years in comparison with males with ulcerative colitis without ileal pouch-anal anastomosis (40.5 children/1000 years), whereas females had reduced birth rates at 27.6 children/1000 years in comparison with females with ulcerative colitis without ileal pouch-anal anastomosis (46.8 children/1000 years). Only birth rates were investigated and not fecundability. Furthermore, there is a question about misattributed paternity, but this has previously been shown to be less than 5%. Ulcerative colitis per se has little impact on birth rates in both sexes, but ileal pouch-anal anastomosis surgery leads to a reduction in birth rates in females and an increase in birth rates in males. This has clinical

Spectrofluorimetric assay method for glutathione and glutathione transferase using monobromobimane.

PubMed

Yakubu, S I; Yakasai, I A; Musa, A

2011-06-01

The primary role of glutathione transferase is to defend an organism from toxicities through catalyzing the reaction of glutathione (GSH) with potentially toxic compounds or metabolites to their chemically and biologically inert conjugates. The objective of the study was to develop a simple and sensitive spectrofluorimetric assay method for glutathione transferase using monobromobimane (MBB), a non fluorescent compound with electrophilic site. MBB slowly reacted with glutathione to form fluorescent glutathione conjugate and that the reaction was catalysed by glutathione transferase. Both non-enzymatic and enzymatic reaction products of MBB, in presence of GSH in phosphate buffer (pH 6.5), were measured by following increase of fluorescence at wavelength of 475nm. For validation of the assay method, the kinetic parameters such as the apparent Michaelis-Mente constants and maximum rates of conjugate formation as well as the specific activity of rat hepatic glutathione transferase were determined. The method was found to be sensitive, thus, applied to measure glutathione contents of crude preparation of rat hepatic cytosol fraction.

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE PAGES

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.; ...

2014-01-01

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Measurement of true ileal phosphorus digestibility in meat and bone meal for broiler chickens.

PubMed

Mutucumarana, R K; Ravindran, V; Ravindran, G; Cowieson, A J

2015-07-01

An experiment was conducted to estimate true ileal phosphorus (P:) digestibility of 3 meat and bone meal samples (MBM-1, MBM-2: , and MBM-3:) for broiler chickens. Four semipurified diets were formulated from each sample to contain graded concentrations of P. The experiment was conducted as a completely randomized design with 6 replicates (6 birds per replicate) per dietary treatment. A total of 432 Ross 308 broilers were assigned at 21 d of age to the 12 test diets. The apparent ileal digestibility coefficient of P was determined by the indicator method, and the linear regression method was used to determine the true P digestibility coefficient. The apparent ileal digestibility coefficient of P in birds fed diets containing MBM-1 and MBM-2 was unaffected by increasing dietary concentrations of P (P > 0.05). The apparent ileal digestibility coefficient of P in birds fed the MBM-3 diets decreased with increasing P concentrations (linear, P < 0.001; quadratic, P < 0. 01). In birds fed the MBM-1 and MBM-2 diets, ileal endogenous P losses were estimated to be 0.049 and 0.142 g/kg DM intake (DMI:), respectively. In birds fed the MBM-3 diets, endogenous P loss was estimated to be negative (-0.370 g/kg DMI). True ileal P digestibility of MBM-1, MBM-2, and MBM-3 was determined to be 0.693, 0.608, and 0.420, respectively. True ileal P digestibility coefficients determined for MBM-1 and MBM-2 were similar (P < 0.05), but were higher (P < 0.05) than that for MBM-3. Total P and true digestible P contents of MBM-1, MBM-2, and MBM-3 were determined to be 37.5 and 26.0; 60.2 and 36.6; and 59.8 and 25.1 g/kg, respectively, on an as-fed basis. © 2015 Poultry Science Association Inc.

Glutathione Degradation.

PubMed

Bachhawat, Anand Kumar; Kaur, Amandeep

2017-11-20

Glutathione degradation has for long been thought to occur only on noncytosolic pools. This is because there has been only one enzyme known to degrade glutathione (γ-glutamyl transpeptidase) and this localizes to either the plasma membrane (mammals, bacteria) or the vacuolar membrane (yeast, plants) and acts on extracellular or vacuolar pools. The last few years have seen the discovery of several new enzymes of glutathione degradation that function in the cytosol, throwing new light on glutathione degradation. Recent Advances: The new enzymes that have been identified in the last few years that can initiate glutathione degradation include the Dug enzyme found in yeast and fungi, the ChaC1 enzyme found among higher eukaryotes, the ChaC2 enzyme found from bacteria to man, and the RipAY enzyme found in some bacteria. These enzymes play roles ranging from housekeeping functions to stress responses and are involved in processes such as embryonic neural development and pathogenesis. In addition to delineating the pathways of glutathione degradation in detail, a critical issue is to find how these new enzymes impact cellular physiology and homeostasis. Glutathione degradation plays a far greater role in cellular physiology than previously envisaged. The differential regulation and differential specificities of various enzymes, each acting on distinct pools, can lead to different consequences to the cell. It is likely that the coming years will see these downstream effects being unraveled in greater detail and will lead to a better understanding and appreciation of glutathione degradation. Antioxid. Redox Signal. 27, 1200-1216.

Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

PubMed Central

Kataoka, Kosuke; Fujihashi, Kohtaro

2009-01-01

In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

Robot-assisted intracorporeal ileal conduit: Marionette technique and initial experience at Roswell Park Cancer Institute.

PubMed

Guru, Khurshid; Seixas-Mikelus, Stéfanie A; Hussain, Abid; Blumenfeld, Aaron J; Nyquist, John; Chandrasekhar, Rameela; Wilding, Gregory E

2010-10-01

To present our technique and initial experience with patients who underwent robot-assisted intracorporeal creation of ileal conduit and to compare them with patients who underwent extracorporeal ileal diversion after robot-assisted radical cystectomy. Twenty-six patients diagnosed with invasive transitional cell carcinoma of the bladder underwent a robot-assisted radical cystectomy with bilateral extended pelvic lymphadenectomy with ileal conduit diversion. Total intracorporeal ileal conduit creation was performed in the last 13 patients. Operative data and short-term outcomes between the 2 groups were assessed. The novel surgical technique for intracorporeal ileal conduit will be presented. The intracorporeal group (IC) included 2 female and 11 male patients (mean age 71 years). The extracorporeal group (EC) included 4 female and 9 male patients (mean age 66 years). No significant differences were noted between the groups in terms of patient age, BMI, sex, prior surgery, or pathologic stage. Overall operative time and intraoperative complications were similar. No significant differences were noted between the 2 groups in terms of diversion time or estimated blood loss. There were 4 complications recorded in IC patients, including nonspecific colitis, small bowel obstruction requiring exploratory laparotomy with lysis of adhesions, a urine leak that eventually resolved but required a temporary nephrostomy tube, and a fever of unknown origin that resolved without intervention. Robot-assisted intracorporeal ileal conduit can be accomplished safely with acceptable operative times even during early experience. Larger series with favorable results will be required to add this new paradigm to minimally invasive surgery for bladder cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report].

PubMed

Andrei, S; Andrei, A; Tonea, A; Andronesi, D; Preda, C; Herlea, V; Popescu, I

2011-01-01

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

Multifaceted Roles of Glutathione and Glutathione-Based Systems in Carcinogenesis and Anticancer Drug Resistance.

PubMed

Hatem, Elie; El Banna, Nadine; Huang, Meng-Er

2017-11-20

Glutathione is the most abundant antioxidant molecule in living organisms and has multiple functions. Intracellular glutathione homeostasis, through its synthesis, consumption, and degradation, is an intricately balanced process. Glutathione levels are often high in tumor cells before treatment, and there is a strong correlation between elevated levels of intracellular glutathione/sustained glutathione-mediated redox activity and resistance to pro-oxidant anticancer therapy. Recent Advances: Ample evidence demonstrates that glutathione and glutathione-based systems are particularly relevant in cancer initiation, progression, and the development of anticancer drug resistance. This review highlights the multifaceted roles of glutathione and glutathione-based systems in carcinogenesis, anticancer drug resistance, and clinical applications. The evidence summarized here underscores the important role played by glutathione and the glutathione-based systems in carcinogenesis and anticancer drug resistance. Future studies should address mechanistic questions regarding the distinct roles of glutathione in different stages of cancer development and cancer cell death. It will be important to study how metabolic alterations in cancer cells can influence glutathione homeostasis. Sensitive approaches to monitor glutathione dynamics in subcellular compartments will be an indispensible step. Therapeutic perspectives should focus on mechanism-based rational drug combinations that are directed against multiple redox targets using effective, specific, and clinically safe inhibitors. This new strategy is expected to produce a synergistic effect, prevent drug resistance, and diminish doses of single drugs. Antioxid. Redox Signal. 27, 1217-1234.

Glutathione in cyanobacteria

NASA Technical Reports Server (NTRS)

Bermudes, D.

1985-01-01

The effects of light and O2 on glutathione production were determined. Results of light and dark studies under normal and reduced oxygen tensions were compared to determine the effect of reduction in oxygen tension on glutathione levels. The growth rate of Anacystis nidulans and concurrent production of glutathione is presented. The generation of time of Anacystis nidulans was approximately 12 hours. Results of light and dark incubation of Aphanothece halophytica dominated planktonic microbial community from Pond 4 and Anacystis nidulans under high and low oxygen tension is also presented. It appears that light grown Anacystis nidulans cells have equal amounts of glutathione while dark grown cells produce more glutathione in the presence of increased O2.

Primary Segmental Volvulus Mimicking Ileal Atresia

PubMed Central

Rao, Sadashiva; B Shetty, Kishan

2013-01-01

Neonatal intestinal volvulus in the absence of malrotation is a rare occurrence and rarer still is the intestinal volvulus in absence of any other predisposing factors. Primary segmental volvulus in neonates is very rare entity, which can have catastrophic outcome if not intervened at appropriate time. We report two such cases, which were preoperatively diagnosed as ileal atresia and intraoperatively revealed to be primary segmental volvulus of the ileum. PMID:26023426

Gross and true ileal digestible amino acid contents of several animal body proteins and their hydrolysates.

PubMed

Cui, J; Chong, B; Rutherfurd, S M; Wilkinson, B; Singh, H; Moughan, P J

2013-07-01

Amino acid compositions of ovine muscle, ovine myofibrillar protein, ovine spleen, ovine liver, bovine blood plasma, bovine blood globulins and bovine serum albumin and the amino acid compositions and in vivo (laboratory rat) true ileal amino acid digestibilities of hydrolysates (sequential hydrolysis with Neutrase, Alcalase and Flavourzyme) of these protein sources were determined. True ileal amino acid digestibility differed (P<0.05) among the seven protein hydrolysates. The ovine myofibrillar protein and liver hydrolysates were the most digestible, with a mean true ileal digestibility across all amino acids of 99%. The least digestible protein hydrolysate was bovine serum albumin with a comparable mean true ileal digestibility of 93%. When the digestible amino acid contents were expressed as proportions relative to lysine, considerable differences, across the diverse protein sources, were found in the pattern of predicted absorbed amino acids. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone.

PubMed

Moeser, Adam J; Nighot, Prashant K; Engelke, Kory J; Ueno, Ryuji; Blikslager, Anthony T

2007-02-01

Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that prostaglandin (PG)E(2) stimulates repair of mucosal barrier function via a mechanism involving Cl(-) secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE(2)-induced mucosal recovery was mediated via type-2 Cl(-) channels (ClC-2). Therefore, the objective of the present study was to directly investigate the role of ClC-2 in mucosal repair by evaluating mucosal recovery in ischemia-injured intestinal mucosa treated with the selective ClC-2 agonist lubiprostone. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers, and short-circuit current (I(sc)) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01-1 microM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 microM lubiprostone stimulating a twofold increase in TER (DeltaTER = 26 Omega.cm(2); P < 0.01). However, lubiprostone (1 microM) stimulated higher elevations in TER despite lower I(sc) responses compared with the nonselective secretory agonist PGE(2) (1 microM). Furthermore, lubiprostone significantly (P < 0.05) reduced mucosal-to-serosal fluxes of (3)H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions. Activation of ClC-2 with the selective agonist lubiprostone stimulated elevations in TER and reductions in mannitol flux in ischemia-injured intestine associated with structural changes in tight junctions. Prostones such as lubiprostone may provide a selective and novel pharmacological mechanism of accelerating recovery of acutely injured intestine compared with the nonselective action of prostaglandins such as PGE(2).

Oral mucositis - self-care

MedlinePlus

Cancer treatment - mucositis; Cancer treatment - mouth pain; Cancer treatment - mouth sores; Chemotherapy - mucositis; Chemotherapy - mouth pain; Chemotherapy - mouth sores; Radiation therapy - mucositis; Radiation therapy - mouth pain; Radiation therapy - mouth ...

Ileal inflammatory fibroid polyp causing chronic ileocolic intussusception and mimicking cecal carcinoma

PubMed Central

Gara, Naveen; Falzarano, John S; Limm, Whitney ML; Namiki, Thomas S; Tom, Laurie KS

2009-01-01

Inflammatory fibroid polyp (IFP) is a rare, idiopathic pseudotumorous lesion of the gastrointestinal tract. While mostly reported as solitary gastric lesions, multiple cases of small bowel IFPs are also reported. It is a documented cause of intussusception in adults. In the case reports of ileal inflammatory fibroid polyps with intussusception, an emergent presentation with small bowel obstruction has been most often described. Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception, anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma. PMID:21160780

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

PubMed

Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

2015-04-01

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

The glutathione cycle: Glutathione metabolism beyond the γ-glutamyl cycle.

PubMed

Bachhawat, Anand Kumar; Yadav, Shambhu

2018-04-17

Glutathione was discovered in 1888, over 125 years ago. Since then, our understanding of various functions and metabolism of this important molecule has grown over these years. But it is only now, in the last decade, that a somewhat complete picture of its metabolism has emerged. Glutathione metabolism has till now been largely depicted and understood by the γ-glutamyl cycle that was proposed in 1970. However, new findings and knowledge particularly on the transport and degradation of glutathione have revealed that many aspects of the γ-glutamyl cycle are incorrect. Despite this, an integrated critical analysis of the cycle has never been undertaken and this has led to the cycle and its errors perpetuating in the literature. This review takes a careful look at the γ-glutamyl cycle and its shortcomings and presents a "glutathione cycle" that captures the current understanding of glutathione metabolism. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Development of an In Vivo and In Vitro Ileal Fermentation Method in a Growing Pig Model.

PubMed

Montoya, Carlos A; de Haas, Edward S; Moughan, Paul J

2018-02-01

Substantial microbial fermentation may occur mainly in the lower small intestine (SI) of human adults, but there is no established methodology to determine this. The study aimed to develop a combined in vivo and in vitro methodology for ileal fermentation based on the pig as an animal model for digestion in human adults. Several aspects of a combined in vivo/in vitro ileal fermentation assay were evaluated. Male 9-wk-old pigs (n = 30; mean ± SD body weight: 23 ± 1.6 kg) were fed a human-type diet (143, 508, 45, 49, and 116 g/kg dry matter diet of crude protein, starch, total lipid, ash, and total dietary fiber) for 15 d. On day 15, pigs were killed, and the last third of the SI was collected to prepare an ileal digesta-based inoculum. Terminal jejunal digesta (last 50 cm of the second third of the SI) were collected as substrate for the assay to test the form of substrate (fresh or freeze-dried), origin (location in jejunum or SI) of the substrate, storage of the inoculum, incubation time (1.2-6.8 h), pH of the medium, and inoculum concentration (6-26 mg inoculum/100 mg substrate). The group of donor pigs used to prepare the inoculum, form of the substrate, origin of the substrate, origin of the inoculum (location in the SI), storage of the inoculum, incubation time, and inoculum concentration did not influence the in vitro ileal organic matter (OM) fermentability (P > 0.05). The in vitro ileal OM fermentability decreased when the pH of the medium increased from 5.5 to 7.5 (31% to 28%; P ≤ 0.05). Predicted (in vivo/in vitro) apparent ileal OM digestibility was similar to the value measured in vivo. Thirty-percent of the terminal jejunal digesta OM was fermented in the ileum. Fiber fermentation in the ileum can be studied using the optimized in vivo/in vitro ileal fermentation method.

Laparoscopic proctocolectomy with ileal j-pouch anal anastomosis in children.

PubMed

Ateş, Ufuk; Ergün, Ergun; Göllü, Gülnur; Küçük, Gönül; Yağmurlu, Aydın

2017-09-01

We aimed to evaluate postoperative fecal incontinence scales of children who underwent laparoscopic proctocolectomy and ileal J-pouch anastomosis for familial adenomateous polyposis (FAP) and inflammatory bowel disease (IBD). Fecal incontinence scores were collected at 3 months post-surgery. A retrospective chart review was also performed to obtain the demographic data and operative technical details. The postoperative Wexner Fecal Incontinence Score was 0 in 9 of 11 patients and satisfactory in the remaining two. None of the children had a major complication. Even though the presented study does not have any comparable data, it seems that laparoscopic total proctocolectomy with ileal J-pouch anal anastomosis (TP IPAA) might be the best choice of surgery because it provides good continence with low complication rates.

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

PubMed

Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

2008-01-01

We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

Study of the effect of ileal distension on the motor activity of the jejunum, and of jejunal distension on the motor activity of the ileum.

PubMed

Shafik, Ahmed; Shafik, Ali A; El, Sibai Olfat; Shafik, Ismail A

2007-01-01

The effect of ileal distension on the jejunal motor activity and ofjejunal distension on the ileal motility have been poorly addressed in the literature. We investigated the hypothesis that distension of either ileum or jejunum would affect the motile activity of the other. Response of jejunal pressure to ileal balloon distension and of ileal pressure to jejunal distension in increments of 2 mL of normal saline were recorded in 18 dogs. The test was performed after individual local anesthetization of the ileum and jejunum and was repeated using saline instead of lidocaine. Ileal distension with 2, 4, and 6mL of saline produced no jejunal pressure response (p >0.05), while 8- and up to 12-mL distension effected jejunal pressure decrease (p<0.05). Jejunal distension up to 6mL did not change ileal pressure (p>0.05); distension with 8, 10, and 12 mL reduced it (p<0.05). Jejunal or ileal pressure responses were maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum did not produce significant pressure changes in either. Jejunal or ileal pressure decrease and presumably hypotonia upon large-volume ileal or jejunal, respectively, distension postulate reflex relationship which we call 'ileal-jejunal and jejuno-ileal inhibitory reflex'. These reflexes appear to regulate chyme flow in small intestine by creating a balance of chyme delivery between the jejunum and ileum. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.

Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

PubMed

Mohan Kumar, M; Joshi, M C; Prabha, T; Dorababu, M; Goel, R K

2006-04-01

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect

Radical cystectomy with W-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples-long term follow-up.

PubMed

Kravchick, Sergey; Lobik, Leonid; Paz, Adrian; Stepnov, Eugeny; Ben-Dor, David; Cytron, Shmuel

2013-01-01

We retrospectively assessed our experience with the W-shaped orthotopic ileal pouch, which was constructed with non-absorbable titanium staples. For these purpose, we discuss the results of bladder capacity, urinary continence and early and long-term postoperative complications. We included in the study 17 patients who underwent radical cystoprostatectomy followed by construction of an orthotopic W-shaped ileal pouch between October 2000 and November 2009. A 65-70 cm segment of ileum was isolated and prearranged into a W-configuration, leaving two 10 cm intact segments on both sides of the ileal fragment. In our technique we entirely anatomized all adjacent limbs in order to create a sphere-shaped pouch. The ureters were directly anastomized to both intact segments of the ileal division. All our patients underwent pouchscopy 6 months after operation and annually. Mean operative time for neobladder reconstruction and ureteral anastomoses was 87 ± 7.67 minutes. In one patient a leak from the ileo-ileal anastomosis was confirmed on the 3rd day after operation. In 2 cases unilateral stricture of the ureteral-neobladder anastomosis was documented. Staple lines were mostly covered with ileal mucosa after 6 months. The mean functional bladder capacity was 340 ± 27.6 mL and 375 ± 43.4 mL at 6 and 12 months, respectively. First-year daytime and nighttime continence was good and acceptable in 90% and 78% of patients, while it increased to 95% during the 2nd year. The long term follow-up shows that non-absorbable titanium staples can be safely used for creation of an orthotopic ileal neobladder. However, these data should be further validated in a larger series of patients.

Successful Embolization of Bleeding Ileal Varices with N-butyl Cyanoacrylate via a Recanalized Paraumbilical Vein.

PubMed

Onishi, Yasuyuki; Kimura, Hiroyuki; Kanagaki, Mitsunori; Oka, Shojiro; Fukumoto, Genki; Otani, Tomoaki; Matsubara, Naoko; Kawabata, Kazuna; Namikawa, Mio; Matsumura, Takeshi; Kimura, Toshiyuki

2018-04-23

A 48-year-old woman with alcoholic liver cirrhosis was admitted to our hospital because of hematochezia and severe anemia. She had been hospitalized many times over the past year for hematochezia of unknown etiology. Contrast-enhanced CT demonstrated ileal varices, which were fed by several ileal veins. These feeding veins were selectively embolized with N-butyl cyanoacrylate (NBCA) via a recanalized paraumbilical vein. The paraumbilical vein instead of the portal vein was punctured to decrease the risk of bleeding complications because she had coagulopathy and ascites. We consider antegrade embolization of ileal varices with NBCA to be a feasible and effective treatment. Access via a paraumbilical vein is an alternative to the transhepatic approach.Level of Evidence Level V, case report.

Mitochondrial Glutathione: Regulation and Functions.

PubMed

Calabrese, Gaetano; Morgan, Bruce; Riemer, Jan

2017-11-20

Mitochondrial glutathione fulfills crucial roles in a number of processes, including iron-sulfur cluster biosynthesis and peroxide detoxification. Recent Advances: Genetically encoded fluorescent probes for the glutathione redox potential (E GSH ) have permitted extensive new insights into the regulation of mitochondrial glutathione redox homeostasis. These probes have revealed that the glutathione pools of the mitochondrial matrix and intermembrane space (IMS) are highly reduced, similar to the cytosolic glutathione pool. The glutathione pool of the IMS is in equilibrium with the cytosolic glutathione pool due to the presence of porins that allow free passage of reduced glutathione (GSH) and oxidized glutathione (GSSG) across the outer mitochondrial membrane. In contrast, limited transport of glutathione across the inner mitochondrial membrane ensures that the matrix glutathione pool is kinetically isolated from the cytosol and IMS. In contrast to the situation in the cytosol, there appears to be extensive crosstalk between the mitochondrial glutathione and thioredoxin systems. Further, both systems appear to be intimately involved in the removal of reactive oxygen species, particularly hydrogen peroxide (H 2 O 2 ), produced in mitochondria. However, a detailed understanding of these interactions remains elusive. We postulate that the application of genetically encoded sensors for glutathione in combination with novel H 2 O 2 probes and conventional biochemical redox state assays will lead to fundamental new insights into mitochondrial redox regulation and reinvigorate research into the physiological relevance of mitochondrial redox changes. Antioxid. Redox Signal. 27, 1162-1177.

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration.

PubMed

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-04-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment.

Quality of life after radical cystectomy for bladder cancer in men with an ileal conduit or continent urinary diversion: A comparative study

PubMed Central

Asgari, M. A.; Safarinejad, M. R.; Shakhssalim, N.; Soleimani, M.; Shahabi, A.; Amini, E.

2013-01-01

Aim: To investigate quality of life (QoL) domains with three forms of urinary diversions, including ileal conduit, MAINZ pouch, and orthotopic ileal neobladder after radical cystectomy in men with muscle-invasive bladder cancer. Materials and Methods: In a prospective study, 149 men underwent radical cystectomy and urinary diversion (70 ileal conduit, 16 MAINZ pouch, and 63 orthotopic ileal neobladder). Different domains of QoL, including general and physical conditions, psychological status, social status, sexual life, diversion-related symptoms, and satisfaction with the treatment were assessed using an author constructed questionnaire. Assessment was performed at three months postoperatively. Results: In questions addressing psychological status, social status, and sexual life, patients with continent diversion had a more favorable outcome (P = 0.002, P = 0.01, and P = 0.002, respectively). The rate of erectile dysfunction did not differ significantly between the three groups (P = 0.21). The rate and global satisfaction was higher with the MAINZ pouch (68.7%) and ileal neobladder (76.2%) as compared with the ileal conduit group (52.8%) (P = 0.002). Conclusion: Continent urinary diversion after radical cystectomy provides better results in terms of QoL as compared with ileal conduit diversion. PMID:24049384

Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Lerner, Aaron; Sabo, Edmund; Krausz, Michael M; Siplovich, Leonardo; Coran, Arnold G; Mogilner, Jorge; Shiloni, Eitan

2003-07-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal morphology and intestinal absorptive function. The purpose of the present study was to determine the effect of enteral ARG supplementation on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Thirty male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-ARG rats underwent bowel resection and were treated with ARG given in the drinking water (2%). Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-ARG animals had a lower jejunal and ileal mucosal weight, jejunal mucosal DNA and protein, ileal mucosal protein, jejunal villus height, jejunal and ileal crypt depth, and enterocyte proliferation index and a greater enterocyte apoptosis compared to SBS untreated animals. We conclude that in a rat model of SBS enteral L-arginine inhibits structural intestinal adaptation. Possible mechanism for this effect may be decreased cell proliferation and increased cell apoptosis.

Measurement of true ileal digestibility of phosphorus in some feed ingredients for broiler chickens.

PubMed

Mutucumarana, R K; Ravindran, V; Ravindran, G; Cowieson, A J

2014-12-01

An experiment was conducted to estimate the true ileal digestibility of P in wheat, sorghum, soybean meal, and corn distiller's dried grains with solubles (DDGS) in broiler chickens. Four semipurified diets were formulated from each ingredient (wheat and sorghum: 236.5, 473, 709.5, and 946 g/kg; soybean meal and corn DDGS: 135, 270, 405, and 540 g/kg) to contain graded concentrations of nonphytate P. The experiment was conducted as a randomized complete block design with 4 weight blocks of 16 cages each (5 birds per cage). A total of 320 21-d-old broilers (Ross 308) were assigned to the 16 test diets with 4 replicates per diet. Apparent ileal digestibility coefficients of P were determined by the indicator method and the linear regression method was used to determine the true P digestibility coefficients. The results showed that the apparent ileal P digestibility coefficients of wheat-based diets were not influenced (P>0.05) by increasing dietary P concentrations, whereas those of diets based on sorghum, soybean meal, and corn DDGS differed (P<0.05) at different P concentrations. Apparent ileal P digestibility in broilers fed diets with soybean meal and corn DDGS linearly (P<0.001) increased with increasing P concentrations. True ileal P digestibility coefficients of wheat, sorghum, soybean meal, and corn DDGS were determined to be 0.464, 0.331, 0.798, and 0.727, respectively. Ileal endogenous P losses in birds fed diets with wheat, soybean meal, and corn DDGS were estimated to be 0.080, 0.609, and 0.418 g/kg DMI, respectively. In birds fed sorghum-based diets, endogenous P losses were estimated to be negative (-0.087 g/kg DMI). True digestible P contents of wheat, sorghum, soybean meal, and corn DDGS were determined to be 1.49, 0.78, 5.16, and 5.94 g/kg, respectively. The corresponding nonphytate P contents in wheat, sorghum, soybean meal, and corn DDGS were 1.11, 0.55, 2.15, and 4.36 g/kg, respectively. These differences between digestible P and nonphytate P

The effect of arginine supplementation on growth hormone release and intestinal mucosal growth after massive small bowel resection in growing rats.

PubMed

Hebiguchi, T; Kato, T; Yoshino, H; Mizuno, M; Koyama, K

1997-08-01

Four-week-old male Sprague-Dawley rats underwent a 90% small bowel resection. From the fourth day after surgery, they were divided into group 1 and 2, and pair-fed by elemental diets (0.8 kcal/mL, 50 mL/day) with L-arginine (n = 10) or L-glycine (n = 11) as an isonitrogenous and isoenergetic supplement for 3 weeks. They were compared with each other 3 weeks after surgery. A statistical analysis was performed using the unpaired Student's t test and the one-way factorial analysis of variance (ANOVA) using Bonferroni/Dunn multiple comparison test. A Pvalue of < .05 was considered significant. There were no significant differences between the two groups in food intake, body weight, tail length, residual ileal length, and plasma IGF-I level. However, the mean height of ileal villi in group 1 showed higher than that in group 2 (P < .01). Growth hormone-releasing hormone (GHRH) provocative tests (1 microg per rat, intravenously) showed the more significant elevation of growth hormone IGH) secretion in the arginine supplement group than that of glycine supplement group at 5 minutes (P < .05). There were no significant differences between basal levels of plasma rat GH in both groups. It is suggested that arginine has a possible significant role of GH secretion and intestinal mucosal growth after massive small bowel resection.

Postnatal development and lymphocyte production of jejunal and ileal Peyer's patches in normal and gnotobiotic pigs.

PubMed Central

Pabst, R; Geist, M; Rothkötter, H J; Fritz, F J

1988-01-01

The development of the number, size, structure and proliferative capacity of Peyer's patches (PP) in the jejunum and ileum has been studied during the early postnatal period of conventional and germ-free pigs. A mean of 15 discrete PP in the jejunum and upper ileum (jejPP) were counted at birth, and the number increased only gradually. A continuous PP is located in the terminal ileum (ileal PP). The length of both jejPP and ileal PP increased with age due to the increase in follicle size and in the number of follicles in the ileal PP. In older pigs, only the ileal PP regressed to small scattered follicles. In germ-free piglets at 39 and 59 days of age, longer PP were found than in normal new-born piglets, but they were significantly shorter than in age-matched controls. Lymphocyte production was studied by the metaphase-arrest technique using vincristine. Lymphocyte production in follicles increased dramatically with age, while in other compartments, such as the inter-follicular and dome area, a low age-independent production of lymphocytes was found. There were no differences in lymphocytopoiesis between jejPP and ileal PP. The present data show major differences in the development, structure and function of PP in pigs in comparison to other species. These species-specific aspects are important for future studies on the immunological function of PP. Images Figure 1 Figure 5 PMID:3410497

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Lerner, Aaron; Coran, Arnold G; Lurie, Michael; Miselevich, Iness; Shiloni, Eitan

2005-06-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

[Comparative study on laparoscopic vaginoplasty using pedicled ileal and sigmoid colon segment transfer].

PubMed

Zhang, Dawei; Zhang, Jun; Wang, Huanying; Li, Bin; Zhu, Xiaoxing; Wang, Liying; Wu, Jixiang

2014-03-01

To study the clinical effect of laparoscopic vaginoplasty using pedicled ileal and sigmoid colon segment. From January 2004 to December 2009, 105 cases undergoing laparoscope-assisted vaginoplasty using a vascularized pedicled intestinal flap were studied retrospectively. Operation time, blood loss in operating, bowel movement after operation, postoperation hospital duration, side effect, and artificial vagina were compared between two surgical management. The vaginoplasty were preformed successfully in all 105 cases. There were 48 patients treated by aparoscope-assisted ileal vaginoplasty and 57 patients treated by laparoscope-assisted sigmoid colon vaginoplasty. The values of the operation time [(141 ± 22) minutes versus (159 ± 18) minutes, P = 0.000], blood loss in operating [(42 ± 6) ml versus (83 ± 14) ml, P = 0.000], bowel movement after operation (36 ± 9) hours versus (68 ± 8) hours(P = 0.000), and postoperation hospital duration [(9.8 ± 2.0) days versus (11.1 ± 1.3) days, P = 0.004] in the sigmoid colon vaginoplasty group were longer or higher than those in ileal vaginoplasty group (P < 0.05).No intraoprative complication occurred. There were four postoperative complications: 2 cases with intestinal obstruction in sigmoid colon vaginoplasty group, 1 case with urethral orifice stenosis and 1 case with vaginal-rectal fistula in ileal vaginoplasty group. At follow-up of 6-62 months, all artificial vaginas had a capacity of over two fingers in wideness and 12-15 cm in length. Vaginal discharges resembled a milky white water or mucus without odour. Fifty-five patients with sexual intercourse reported satisfactory results.Six patients complained vaginal stenosis:5 patients in ileal vaginoplasty group and 1 patient in sigmoid colon vaginoplasty group. Laparoscope-assisted vaginoplasty using pedicled ileum or sigmoid colon segment are both the effective ways in forming vagina. The latter management takes more time and blood loss while operating, yet the

Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration

PubMed Central

Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

2009-01-01

A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment. PMID:27956966

The influence of soy oligosaccharides on apparent and true ileal amino acid digestibilities and fecal consistency in growing pigs.

PubMed

Smiricky, M R; Grieshop, C M; Albin, D M; Wubben, J E; Gabert, V M; Fahey, G C

2002-09-01

Fourteen ileally cannulated pigs (BW = 35 +/- 2 kg) were randomly allotted to a replicated 7 x 7 Latin square design experiment to evaluate the influence of the soybean oligosaccharides (OS), raffinose and stachyose, on ileal nutrient digestibility and fecal consistency. Semipurified diets containing soy protein concentrate (SPC) or soybean meal (SBM) as the sole protein sources were fed. Soy solubles (SS), a by-product of SBM processing containing 3.5% raffinose and 11.5% stachyose, were used to increase dietary raffinose and stachyose concentrations. The seven dietary treatments were SPC, SPC + 9% SS, SBM, SBM + 9% SS, SBM + 18% SS, SBM + 24,000 U alpha-galactosidase enzyme preparation/kg diet, and a low-protein casein (LPC) diet used to calculate true digestibility. Diets, with the exception of the LPC diet, were formulated to contain 17% CP. All diets contained 0.5% chromic oxide as a marker for ileal digestibility determination. The experimental periods were divided into a 5-d diet adaptation followed by 2-d of ileal digesta collection. Diets and digesta were analyzed for DM, N, Cr, amino acids (AA), raffinose, and stachyose. Fecal consistency was determined on d 6 and 7 of each experimental period. The apparent and true ileal AA digestibilities were not different (P < 0.05) for the SPC and SBM control diets. When SS was added to the SPC diet, apparent and true N and AA digestibilities were depressed (P < 0.05) with the exception of Trp and Pro. The apparent and true ileal N and AA digestibilities were not different (P > 0.05) between the SBM control and SBM + 9% SS diets with the exception of Glu. There was a linear decrease (P < 0.05) in apparent and true DM, Val, Gly, and Tyr digestibilities when increasing levels of SS were added to the SBM diet. The addition of alpha-galactosidase did not improve apparent or true ileal N or AA digestibilities except for apparent and true Val and Tyr. Ileal raffinose digestibility was improved (P < 0.05) by addition of a

Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats.

PubMed

Ramzy, A R; Nausheen, S; Chelikani, P K

2014-03-01

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower

Herbs in Oral Mucositis

PubMed Central

Baharvand, Maryam; Jafari, Soudeh

2017-01-01

Oral mucositis is an inflammatory mucosal destruction as a result of chemotherapy and/or radiation therapy, which in severe cases can impair patients’ quality of life. Moreover, mucosal infection and/or systemic involvement due to compromised immunity leads to delay or discontinuation of the treatment. Many strategies and agents have been suggested for the management of this condition. Because of their lower side effects compared to chemical drugs, general interest in evaluating therapeutic effects of herbs has been increased intensively. Herbal plants apply their effect through different mechanisms of action: antioxidant, analgesic, anti-inflammatory, antifungal, antiseptic, and anticarcinogenic activity. Recently, various natural agents in plants have been noticed in mucositis, which may improve the symptoms through different interventions. The purpose of this review is to focus on the preventive or therapeutic use of herbal medicine to alleviate oral mucositis. PMID:28511530

Why mucosal health?

USDA-ARS?s Scientific Manuscript database

Aquaculture species depend more heavily on mucosal barriers than their terrestrial agricultural counterparts as they are continuously interacting with the aquatic microbiota. Unlike classical immune centers, such as the spleen and kidney, the accessibility of mucosal surfaces through immersion/dip t...

Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Skinner, Eila C; Fairey, Adrian S; Groshen, Susan; Daneshmand, Siamak; Cai, Jie; Miranda, Gus; Skinner, Donald G

2015-08-01

The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures

Study of the effect of jejuno-ileal distension on the motor activity of the stomach with evidence of "entero-gastric inhibitory reflex".

PubMed

Shafik, Ahmed; Shafik, Ali A; el-Sibai, Olfat

2003-01-01

In chronic constipation due to delayed colonic transit, stasis of the ileal contents with resulting ileal distension may occur. The current study investigated the effect of ileal and jejunal distension on the gastric motility, aiming at elucidating the possible existence of a relationship and its role in the flow through the gut. The response of the gastric pressure to ileal and jejunal balloon distension in increments of 2 mL of saline was recorded in 12 mongrel dogs. The test was repeated after separate local anesthetization of the ileum, jejunum and stomach. 2- and 4-mL ileal balloon distension produced no significant gastric pressure response, while 6- and up to 10-mL distension effected decrease of the antral and corporeal pressures (p < 0.05, p < 0.05, respectively). Jejunal distension produced a gastric pressure decline (p < 0.05) with 4 and up to 10 mL of saline. The gastric pressure decrease did not show significant changes with the various distending volumes. It was maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum caused no gastric pressure changes, nor did ileal or jejunal distension produce pressure changes in the anesthetized stomach. The gastric pressure decline and presumably hypotonia upon ileal or jejunal distension with big volumes postulate a reflex relationship which we call "entero-gastric inhibitory reflex". The small intestine is suggested to slow down gastric emptying through this reflex. A balance is thus created between chyme delivery from the stomach and chyme processing by the small intestine. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.

Primary mucosal melanomas: a comprehensive review

PubMed Central

Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

2012-01-01

Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas. PMID:23071856

Primary mucosal melanomas: a comprehensive review.

PubMed

Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

2012-01-01

Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas.

Glutathione Levels in Human Tumors

PubMed Central

Gamcsik, Michael P.; Kasibhatla, Mohit S.; Teeter, Stephanie D.; Colvin, O. Michael

2013-01-01

This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker. PMID:22900535

Glutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead.

PubMed

Dobrakowski, Michał; Pawlas, Natalia; Hudziec, Edyta; Kozłowska, Agnieszka; Mikołajczyk, Agnieszka; Birkner, Ewa; Kasperczyk, Sławomir

2016-07-01

The aim of the study was to investigate the influence of subacute exposure to lead on the glutathione-related antioxidant defense and oxidative stress parameters in 36 males occupationally exposed to lead for 40±3.2days. Blood lead level in the examined population increased significantly by 359% due to lead exposure. Simultaneously, erythrocyte glutathione level decreased by 16%, whereas the activity of glutathione-6-phosphate dehydrogenase in erythrocytes and leukocytes decreased by 28% and 10%, respectively. Similarly, the activity of glutathione-S-transferase in erythrocytes decreased by 45%. However, the activity of glutathione reductase in erythrocytes and leukocytes increased by 26% and 6%, respectively, whereas the total oxidant status value in leukocytes increased by 37%. Subacute exposure to lead results in glutathione pool depletion and accumulation of lipid peroxidation products; however, it does not cause DNA damage. Besides, subacute exposure to lead modifies the activity of glutathione-related enzymes. Copyright © 2016 Elsevier B.V. All rights reserved.

Disseminated histoplasmosis presenting with ileal perforation in a renal transplant recipient.

PubMed

Zainudin, B M; Kassim, F; Annuar, N M; Lim, C S; Ghazali, A K; Murad, Z

1992-08-01

A renal transplant patient presented with ileal perforation due to histoplasmosis 3 years after transplantation. Mesenteric lymph nodes and lungs were also affected by the disease. She was successfully treated with amphotericin B followed by ketoconazole.

New frontiers in mucositis.

PubMed

Peterson, Douglas E; Keefe, Dorothy M; Sonis, Stephen T

2012-01-01

Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

Interrelations between the microbiotas in the litter and in the intestines of commercial broiler chickens.

PubMed

Cressman, Michael D; Yu, Zhongtang; Nelson, Michael C; Moeller, Steven J; Lilburn, Michael S; Zerby, Henry N

2010-10-01

The intestinal microbiota of broiler chickens and the microbiota in the litter have been well studied, but the interactions between these two microbiotas remain to be determined. Therefore, we examined their reciprocal effects by analyzing the intestinal microbiotas of broilers reared on fresh pine shavings versus reused litter, as well as the litter microbiota over a 6-week cycle. Composite ileal mucosal and cecal luminal samples from birds (n = 10) reared with both litter conditions (fresh versus reused) were collected at 7, 14, 21, and 42 days of age. Litter samples were also collected at days 7, 14, 21, and 42. The microbiotas were profiled and compared within sample types based on litter condition using PCR and denaturing gradient gel electrophoresis (PCR-DGGE). The microbiotas were further analyzed using 16S rRNA gene clone libraries constructed from microbiota DNA extracted from both chick intestinal and litter samples collected at day 7. Results showed significant reciprocal effects between the microbiotas present in the litter and those in the intestines of broilers. Fresh litter had more environmental bacteria, while reused litter contained more bacteria of intestinal origin. Lactobacillus spp. dominated the ileal mucosal microbiota of fresh-litter chicks, while a group of bacteria yet to be classified within Clostridiales dominated in the ileal mucosal microbiota in the reused-litter chicks. The Litter condition (fresh versus reused) seemed to have a more profound impact on the ileal microbiota than on the cecal microbiota. The data suggest that the influence of fresh litter on ileal microbiota decreased as broilers grew, compared with temporal changes observed under reused-litter rearing conditions.

Glutathione conjugation and contaminant transformation

USGS Publications Warehouse

Field, Jennifer A.; Thurman, E.M.

1996-01-01

The recent identification of a novel sulfonated metabolite of alachlor in groundwater and metolachlor in soil is likely the result of glutathione conjugation. Glutathione conjugation is an important biochemical reaction that leads, in the case of alachlor, to the formation of a rather difficult to detect, water-soluble, and therefore highly mobile, sulfonated metabolite. Research from weed science, toxicology, and biochemistry is discussed to support the hypothesis that glutathione conjugation is a potentially important detoxification pathway carried out by aquatic and terrestrial plants and soil microorganisms. A brief review of the biochemical basis for glutathione conjugation is presented. We recommend that multidisciplinary research focus on the occurrence and expression of glutathione and its attendant enzymes in plants and microorganisms, relationships between electrophilic substrate structure and enzyme activity, and the potential exploitation of plants and microorganisms that are competent in glutathione conjugation for phytoremediation and bioremediation.

Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.

PubMed

Holroyd, K J; Buhl, R; Borok, Z; Roum, J H; Bokser, A D; Grimes, G J; Czerski, D; Cantin, A M; Crystal, R G

1993-10-01

Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence. Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration. Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed. It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals.

Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.

PubMed Central

Holroyd, K. J.; Buhl, R.; Borok, Z.; Roum, J. H.; Bokser, A. D.; Grimes, G. J.; Czerski, D.; Cantin, A. M.; Crystal, R. G.

1993-01-01

BACKGROUND--Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence. METHODS--Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration. RESULTS--Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed. CONCLUSIONS--It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals. PMID:8256245

Recombinant poxviruses as mucosal vaccine vectors.

PubMed

Gherardi, M Magdalena; Esteban, Mariano

2005-11-01

The majority of infections initiate their departure from a mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of mucosal immunity is a high priority in the development of vaccines against mucosal pathogens. The selection of an appropriate antigen delivery system is necessary to induce an efficient mucosal immune response. Poxvirus vectors have been the most intensively studied live recombinant vector, and numerous studies have demonstrated their ability to induce mucosal immune responses against foreign expressed antigens. Previous studies have demonstrated that recombinants based on the attenuated modified vaccinia virus Ankara (MVA) vector were effective in inducing protective responses against different respiratory viruses, such as influenza and respiratory syncytial virus, following immunization via mucosal routes. Recent studies performed in the murine and macaque models have shown that recombinant MVA (rMVA) does not only stimulate HIV-specific immunity in the genital and rectal tracts following mucosal delivery, but can also control simian/human immunodeficiency viraemia and disease progression. In addition, a prime-boost vaccination approach against tuberculosis emphasized the importance of the intranasal rMVA antigen delivery to induce protective immunity against Mycobacterium tuberculosis. The aim of this review is to summarize the studies employing recombinant poxviruses, specifically rMVA as a mucosal delivery vector. The results demonstrate that rMVAs can activate specific immune responses at mucosal surfaces, and encourage further studies to characterize and improve the MVA mucosal immunogenicity of poxvirus vectors.

Sulfasalazine in Prevention of Pouchitis After Proctocolectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

PubMed

Scaioli, Eleonora; Sartini, Alessandro; Liverani, Elisa; Digby, Richard John; Ugolini, Giampaolo; Rosati, Giancarlo; Poggioli, Gilberto; Festi, Davide; Bazzoli, Franco; Belluzzi, Andrea

2017-04-01

Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for refractory ulcerative colitis. A non-standardized preventative treatment exists. Sulfasalazine has proved effective in acute pouchitis therapy. The aim of this study was to retrospectively evaluate the effect of sulfasalazine in primary prophylaxis of pouchitis after proctocolectomy with ileal pouch-anal anastomosis. Data files of patients who underwent total proctocolectomy with ileal pouch-anal anastomosis for refractory ulcerative colitis and/or dysplasia from January 2007 to December 2014, with a follow-up until August 2015, were analyzed. After closure of loop ileostomy, on a voluntary basis, patients received a primary prophylaxis of pouchitis with sulfasalazine (2000 mg per day) continually until acute pouchitis flare and/or drop out due to side effects. Follow-up data were available for 51 of the 55 surgical patients. Median follow-up time was 68 months (range 10-104). Thirty postoperative complications occurred in 25 patients. 45% of patients developed pouchitis. Sulfasalazine prophylaxis was administered in 39.2% of patients; 15% of the these developed pouchitis versus 64.5% (20/31) of the non-sulfasalazine patients (p < 0.001). Pouchitis-free survival curves were 90.55 months in sulfasalazine patients and 44.46 in non-sulfasalazine patients (log-rank test p = 0.001, Breslow p = 0.001). Sulfasalazine may be potentially administered in pouchitis prophylaxis after proctocolectomy with ileal pouch-anal anastomosis, but large prospectively controlled trials are needed.

Mucosal immunity and probiotics in fish.

PubMed

Lazado, Carlo C; Caipang, Christopher Marlowe A

2014-07-01

Teleost mucosal immunity has become the subject of unprecedented research studies in recent years because of its diversity and defining characteristics. Its immune repertoire is governed by the mucosa-associated lymphoid tissues (MALT) which are divided into gut-associated lymphoid tissues (GALT), skin-associated lymphoid tissues (SALT), and gill-associated lymphoid tissues (GIALT). The direct contact with its immediate environment makes the mucosal surfaces of fish susceptible to a wide variety of pathogens. The inherent immunocompetent cells and factors in the mucosal surfaces together with the commensal microbiota have pivotal role against pathogens. Immunomodulation is a popular prophylactic strategy in teleost and probiotics possess this beneficial feature. Most of the studies on the immunomodulatory properties of probiotics in fish mainly discussed their impacts on systemic immunity. In contrast, few of these studies discussed the immunomodulatory features of probiotics in mucosal surfaces and are concentrated on the influences in the gut. Significant attention should be devoted in understanding the relationship of mucosal immunity and probiotics as the present knowledge is limited and are mostly based on extrapolations of studies in humans and terrestrial vertebrates. In the course of the advancement of mucosal immunity and probiotics, new perspectives in probiotics research, e.g., probiogenomics have emerged. This review affirms the relevance of probiotics in the mucosal immunity of fish by revisiting and bridging the current knowledge on teleost mucosal immunity, mucosal microbiota and immunomodulation of mucosal surfaces by probiotics. Expanding the knowledge of immunomodulatory properties of probiotics especially on mucosal immunity is essential in advancing the use of probiotics as a sustainable and viable strategy for successful fish husbandry. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Shamir, Raanan; Shehadeh, Naim; Bejar, Jacob; Hirsh, Mark; Coran, Arnold G

2005-03-01

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Novel vaccine development strategies for inducing mucosal immunity

PubMed Central

Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

2012-01-01

To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

Zinc Oxide Nanoparticles Influence Microflora in Ileal Digesta and Correlate Well with Blood Metabolites.

PubMed

Feng, Yanni; Min, Lingjiang; Zhang, Weidong; Liu, Jing; Hou, Zhumei; Chu, Meiqiang; Li, Lan; Shen, Wei; Zhao, Yong; Zhang, Hongfu

2017-01-01

Zinc oxide nanoparticles (ZnO NPs) are used widely in consumer and industrial products, however, their influence on gut microbiota and metabolism and their mutual interactions are not fully understood. In this study, the effects of ZnO NPs on ileal bacterial communities, plasma metabolites, and correlations between them were investigated. Hens were fed with different concentrations of ZnO NPs [based on Zn; 0 mg/kg (control), 25 mg/kg, 50 mg/kg, and 100 mg/kg] for 9 weeks. Subsequently, ileal digesta and blood plasma were collected for analysis of microflora and metabolites, respectively. The V3-V4 region of the 16S rRNA gene of ileal digesta microbiota was sequenced using the Illumina HiSeq 2500 platform. The predominant bacterial community in the ileum belongs to the phylum Firmicutes. The richness of the bacterial community was negatively correlated with increasing amounts of ZnO NPs ( r = -0.636, P < 0.01); when ZnO NP levels were at 100 mg/kg, microbiota diversity was significantly decreased ( P < 0.05). The community structure determined by LEfSe analysis indicated that Bacilli, Fusobacteria, and Proteobacteria were changed, and Lactobacillus was reduced by ZnO NPs. Moreover, metabolism as analyzed by nuclear magnetic resonance (NMR) indicated that glucose, some amino acids, and other metabolites were changed by ZnO NPs. Choline, lactate, and methionine were positively correlated with bacterial richness. In summary, ZnO NPs could influence the levels of microflora in ileal digesta, particularly Lactobacillus . Furthermore, the richness of the microbiota was related to changes in choline, lactate, and methionine metabolism.

Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation.

PubMed

Mosińska, Paula; Fichna, Jakub; Storr, Martin

2015-06-28

Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

Normal Tissue Complication Probability (NTCP) Modelling of Severe Acute Mucositis using a Novel Oral Mucosal Surface Organ at Risk.

PubMed

Dean, J A; Welsh, L C; Wong, K H; Aleksic, A; Dunne, E; Islam, M R; Patel, A; Patel, P; Petkar, I; Phillips, I; Sham, J; Schick, U; Newbold, K L; Bhide, S A; Harrington, K J; Nutting, C M; Gulliford, S L

2017-04-01

A normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR. Predictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data. Penalised logistic regression and random forest classification (RFC) models were generated for both OARs and compared. Internal validation was carried out with 100-iteration stratified shuffle split cross-validation, using multiple metrics to assess different aspects of model performance. Associations between treatment covariates and severe mucositis were explored using RFC feature importance. Penalised logistic regression and RFC models using the oral cavity OAR performed at least as well as the models using mucosal surface OAR. Associations between dose metrics and severe mucositis were similar between the mucosal surface and oral cavity models. The volumes of oral cavity or mucosal surface receiving intermediate and high doses were most strongly associated with severe mucositis. The simpler oral cavity OAR should be preferred over the mucosal surface OAR for NTCP modelling of severe mucositis. We recommend minimising the volume of mucosa receiving intermediate and high doses, where possible. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Linking ileal digestible phosphorus and bone mineralization in broiler chickens fed diets supplemented with phytase and highly soluble calcium.

PubMed

Adeola, O; Walk, C L

2013-08-01

The objectives of this study were to determine the ileal digestibility of P in potassium phosphate, phytase-related ileal digestible P release, bone-mineralization-based ileal digestible P equivalency of phytase, and phytase-related efficiency of ileal digestible P utilization for bone mineralization in broiler chickens at 2 dietary concentrations of highly soluble Ca (HSC). Birds were sorted by BW at d 15 posthatch and assigned to 8 cages per diet with 8 birds per cage. Twelve diets were arranged in a 2 × 6 factorial of HSC at 5 or 6 g/kg and P supply treatment at 6 levels consisting of 4 added P levels (P from KH2PO4 added at 0, 0.7, 1.4, or 2.1 g/kg of diet) or 2 added phytase levels (500 or 1,000 phytase units). On d 24 posthatch, ileal digesta were collected for ileal P digestibility (IPD) determination and the left tibia was collected from the 4 heaviest birds in each cage for bone ash determination. Weight gain, G:F, and tibia ash were higher (P < 0.05) at 5 than at 6 g of HSC/kg. Added P from KH2PO4 or added phytase linearly increased (P < 0.001) weight gain, G:F, tibia ash, and IPD. The IPD of KH2PO4 derived from multiple linear regressions of digestible on total P intake for the diets without added phytase showed a reduction (P < 0.05) from 89.5 to 84.5% with increased HSC from 5 to 6 g/kg. Polynomial regressions of digestible P intake on phytase intake indicated that 1,000 units of added phytase released 1.701 or 1.561 g of digestible P in diets containing 5 or 6 g of added HSC/kg, respectively. Polynomial regressions of tibia ash on digestible P or phytase intake in diets containing 5 or 6 g of added HSC/kg at 1,000 phytase units gave digestible P equivalency of 1.487 or 1.448 g, respectively. Thus, phytase-related efficiency of ileal digestible P utilization for bone mineralization was 87.4 and 92.8% in diets containing 5 or 6 g of added HSC/kg, respectively.

Biology and Mucosal Immunity to Myxozoans

PubMed Central

Gómez, Daniela; Bartholomew, Jerri; Sunyer, J. Oriol

2014-01-01

Myxozoans are among the most abundant parasites in nature. Their life cycles involve two hosts: an invertebrate, usually an annelid, and a vertebrate, usually a fish. They affect fish species in their natural habitats but also constitute a menace for fish aquaculture. Using different strategies they are able to parasitize and cause damage in multiple organs, including mucosal tissues, which they use also as portals of entry. In fish, the main mucosal sites include the intestine, skin and gills. Recently the finding of a specific mucosal immunoglobulin in teleost (IgT), analogous to mammalian IgA, and the capacity of fish to develop a specific mucosal immune response against different pathogens, has highlighted the importance of studying immune responses at mucosal sites. In this review, we describe the major biological characteristics of myxozoan parasites and present the data available regarding immune responses for species that infect mucosal sites. As models for mucosal immunity we review the responses to Enteromyxum spp. and Ceratomyxa shasta, both of which parasitize the intestine. The immune response at the skin and gills is also described, as these mucosal tissues are used by myxozoans as attaching surfaces and portal of entry, and some species also parasitize these sites. Finally, the development of immunoprophylactic strategies is discussed. PMID:23994774

Determining the activity of mucosal adjuvants.

PubMed

Baudner, Barbara C; Giudice, Giuseppe Del

2010-01-01

Mucosal vaccination offers the advantage of blocking pathogens at the portal of entry, improving patient's compliance, facilitating vaccine delivery, and decreasing the risk of unwanted spread of infectious agents via contaminated syringes.Recent advances in vaccinology have created an array of vaccine constructs that can be delivered to mucosal surfaces of the respiratory, gastrointestinal, and genitourinary tracts using intranasal, oral, and vaginal routes. Due to the different characteristics of mucosal immune response, as compared with systemic response, mucosal immunization requires particular methods of antigen presentation. Well-tolerated adjuvants that enhance the efficacy of such vaccines will play an important role in mucosal immunization. Among promising mucosal adjuvants, mutants of cholera toxin and the closely related heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli present powerful tools, augmenting the local and systemic serum antibody response to co-administered antigens.In this chapter, we describe the formulation and application of vaccines using the genetically modified LTK63 mutant as a prototype of the family of these mucosal adjuvants and the tools to determine its activity in the mouse model.

Intestinal mucositis: mechanisms and management.

PubMed

Keefe, Dorothy M

2007-07-01

To describe the advances in the rapidly evolving field of intestinal (or alimentary) mucositis during the past year. Major advances have been made in both the clinical and preclinical setting, with the publication of a suite of articles regarding the pathobiology and management of mucositis, as well as several articles on important basic research in the area. The mechanism of mucositis development is now understood to be much more complex than previously thought, with an interplay of host and drug factors leading to overt damage, and variation in manifestation of that damage depending on the specific region of the gut. The MASCC/ISOO management guidelines for mucositis have been updated: a recommendation for the use of palifermin in the hematology transplant setting has been added, and a couple of previous recommendations have been revoked. This marks an important milestone in mucositis, as it is the first time a drug has been available that substantially reduces the occurrence and severity of mucositis. There is still much to be done to abolish the severe toxicity of chemotherapy and radiotherapy; however, progress is accelerating, and new targeted drugs are becoming available.

Determining Glutathione Levels in Plants.

PubMed

Sahoo, Smita; Awasthi, Jay Prakash; Sunkar, Ramanjulu; Panda, Sanjib Kumar

2017-01-01

Upon exposure to abiotic stresses, plants tend to accumulate excessive amounts of reactive oxygen species (ROS) that inturn react with cellular lipids, proteins, and DNA. Therefore, decreasing ROS accumulation is indispensible to survive under stress, which is accomplished by inducing enzymatic and nonenzymatic antioxidant defense pathways. Glutathione, particularly reduced glutathione (GSH), represents a principal anitioxidant that could decrease ROS through scavenging them directly or indirectly through ascorbate-glutathione cycle or GSH peroxidases. Glutathione content can be determined using HPLC or spectrophotometric assays. In this chapter, we provided detailed assays to determine total, reduced, and oxidized gluathione using spectrophotometric method.

Multicolor spectral karyotype analysis of a transplantable human ileal carcinoid.

PubMed

Sjögren, H; Nilsson, O; Behrendt, M; Kölby, L; Jacobsen Levin, A M; Ahlman, H; Stenman, G

2000-12-01

In this report we present the results of a combined cytogenetic and multicolor spectral karyotype (SKY) analysis of a transplantable human ileal carcinoid (GOT1). By using SKY it was possible to identify the origin and organization of all clonal marker chromosomes and to identify cryptic translocations not detectable by conventional chromosome banding. The stemline karyotype of low passage GOT1 cells was interpreted as 43,XX, der(1)del(1)(?), inv(2)(p25q13), del(3)(p21), del(5)(q13q31), del(6)(q13), -9, -13, -15, del(16) (q22). Analysis of the GOT1 cells after about 2.5 years of propagation in nude mice allowed us to follow the in vivo progression of this tumor. Relatively few additional rearrangements had occurred during this period, indicating that the GOT1 cells are genetically stable. Most of the abnormalities detected result in loss of whole or parts of chromosomes, suggesting that loss of multiple chromosomal regions, presumably containing tumor suppressor genes, might be important genetic events in ileal carcinoids.

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

PubMed Central

Johnson, William M.; Wilson-Delfosse, Amy L.; Mieyal, John. J.

2012-01-01

Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated. PMID:23201762

Mucosal immunization: a review of strategies and challenges.

PubMed

Patel, Hinal; Yewale, Chetan; Rathi, Mohan N; Misra, Ambikanandan

2014-01-01

The vast majority of pathogens enter the human body via the mucosal surfaces of the gastrointestinal, respiratory, and urogenital tracts, where they initiate mucosal infections that lead to systemic infections. Despite strong evidence that a good mucosal immune response can effectively prevent systemic infection too, only a few mucosal vaccines are available due to their low efficiency. Most current immunization techniques involve systemic injection, but they are ineffective to induce immunization at a mucosal site. It is a great challenge to target a mucosal compartment that can induce protective immunity at mucosal sites as well as systemic sites. A better understanding of cellular and molecular factors involved in the regulation of mucosal immunity will aid in the design of safer mucosal vaccines that elicit the desired protective immunity against infectious diseases such as HIV. The development of mucosal vaccines, whether for prevention of infectious diseases or for immunotherapy, requires antigen delivery and adjuvant systems that can effectively present vaccine or immunotherapeutic antigens to the mucosal sites. In this review, we examine the mechanism of mucosal protection, induction of mucosal immune response, types of vaccines, current status of marketed vaccines, and novel strategies for protection against infections and for treatment of inflammatory disorders. Additionally, we offer perspectives on future challenges and research directions.

Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis

PubMed Central

Sherif, Lobna S.; Raouf, Randaa K. Abdel; Sayede, Rokaya M. El; Wakkadd, Amany S. El; Shoaib, Ashraf R.; Ali, Hanan M.; Refay, Amira S. El

2015-01-01

BACKGROUND: Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. AIM: This study was designed to assess if mucosal integrity “measured by secretory IgA (SIgA)” is a protective factor from more epithelial alteration “measured by glutathione transferase” in infants with Rota gastroenteritis and its relation to infants’ feeding pattern. PATIENTS AND METHODS: This study was conducted on 79 infants aged 6 months and less from those diagnosed as having gastroenteritis and admitted to Gastroenteritis Department in Abo El Rish Pediatric Hospital, Cairo University. Plasma glutathione s-transferases and Stool SIgA were measured using ELISA technique. Rota virus detection was done by Reverse transcriptase PCR. RESULTS: SIgA was found to be significantly positive in exclusive breast fed infants, Glutathione transferase was significantly more frequently positive in Rota positive cases than Rota negative cases by Reverse transcriptase PCR. A significant negative correlation between Glutathione transferase and Secretory IgA was found, (p < 0.05). CONCLUSION: Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis. PMID:27275307

Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

PubMed

De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

2012-02-01

To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

Passive regeneration of glutathione: glutathione reductase regulation in the freeze-tolerant North American wood frog, Rana sylvatica.

PubMed

Dawson, Neal J; Storey, Kenneth B

2017-09-01

Wood frogs inhabit a broad range across North America, extending from the southern tip of the Appalachian Mountains to the northern boreal forest. Remarkably, they can survive the winter in a frozen state, where as much as 70% of their body water is converted into ice. Whilst in the frozen state, their hearts cease to pump blood, causing their cells to experience ischemia, which can dramatically increase the production of reactive oxygen species within the cell. To overcome this, wood frogs have elevated levels of glutathione, a primary antioxidant. We examined the regulation of glutathione reductase, the enzyme involved in recycling glutathione, in both the frozen and unfrozen (control) state. Glutathione reductase activity from both the control and frozen state showed a dramatic reduction in substrate specificity ( K m ) for oxidized glutathione (50%) when measured in the presence of glucose (300 mmol l -1 ) and a increase (157%) when measured in the presence of levels of urea (75 mmol l -1 ) encountered in the frozen state. However, when we tested the synergistic effect of urea and glucose simultaneously, we observed a substantial reduction in the K m for oxidized glutathione (43%) to a value similar to that with glucose alone. In fact, we found no observable differences in the kinetic and structural properties of glutathione reductase between the two states. Therefore, a significant increase in the affinity for oxidized glutathione in the presence of endogenous levels of glucose suggests that increased glutathione recycling may occur as a result of passive regulation of glutathione reductase by rising levels of glucose during freezing. © 2017. Published by The Company of Biologists Ltd.

Expression of mucins in the mucosal surface of small intestines in 1 week-old pigs.

PubMed

Kim, Chung Hyun; Oh, Yeonsu; Ha, Yooncheol; Ahn, Qwein; Kim, Sung-Hoon; Cho, Kyung-Dong; Lee, Bog-Hieu; Chae, Chanhee

2010-02-01

The aim of this study was to determine the immunoexpression of mucins in jejunal and ileal villous epithelium using six antibodies against MUC1, MUC2, MUC4 MUC5AC, MUC5B and MUC6. The immunohistochemical score for MUC1 has significantly intense staining compared with MUC2 (P=0.008) and the immunohistochemical socre for MUC4 and MUC 6 has significantly intense staining compared with MUC2 (P=0.032) in ileal villous surface. The immunohistochemical score for MUC4 (P=0.008), MUC5AC (P=0.016) and MUC6 (P=0.016) in ileal villous surface has significantly intense staining compared with ileal cryptic surface. The results of this study demonstrated that six mucins gave distinctly different expression patterns throughout the 1 week-old porcine small intestinal tract.

Taeniasis: A possible cause of ileal bleeding.

PubMed

Settesoldi, Alessia; Tozzi, Alessandro; Tarantino, Ottaviano

2017-12-16

Taenia spp. are flatworms of the class Cestoda, whose definitive hosts are humans and primates. Human infestation (taeniasis) results from the ingestion of raw meat contaminated with encysted larval tapeworms and is considered relatively harmless and mostly asymptomatic. Anemia is not recognized as a possible sign of taeniasis and taeniasis-induced hemorrhage is not described in medical books. Its therapy is based on anthelmintics such praziquantel, niclosamide or albendazole. Here we describe a case of acute ileal bleeding in an Italian man affected with both Taenia spp. infestation resistant to albendazole and Helicobacter pylori -associated duodenal ulcers.

Endobronchial Mucosal Neuroma with Sarcoidosis.

PubMed

Erdem, Ipek; Duman, Dildar; Eroglu, Selma; Agca, Meltem; Erdagi, Aykut; Turker, Hatice; Hazar, Armagan

2018-02-01

A first case of endobronchial mucosal neuroma with sarcoidosis is hereby reported. A 67-year female patient, who was diagnosed as sarcoidosis previously, was admitted to our hospital with symptoms of dyspnea, chest pain and fatigue. Middle lobe atelectasis and endobronchial lesion were observed in thorax computed tomography (CT). Fiberoptic bronchoscopy revealed polypoid lesions and histopathological examination of biopsy material showed clustered nerve bundles consistent with mucosal neuroma and non-necrotising granulomas consistent with sarcoidosis. Mucosal neuromas are pathognomonic features of multiple endocrine neoplasia (MEN) type 2B. But other components of MEN type 2B such as medullary tyroid carcinoma or pheochromocytoma were not detected in our patient. Hence, a diagnosis of solitary mucosal neuroma and sarcoidosis in the bronchi was made.

Update on primary mucosal melanoma.

PubMed

Tacastacas, Joselin D; Bray, Julie; Cohen, Yoon K; Arbesman, Joshua; Kim, Julian; Koon, Henry B; Honda, Kord; Cooper, Kevin D; Gerstenblith, Meg R

2014-08-01

Mucosal melanomas are aggressive cancers of mucosal surfaces with clinical and pathologic characteristics distinct from cutaneous melanomas, warranting different staging systems and treatment approaches. Surgical resection is performed frequently for the primary tumor, although the utility of lymph node surgery and radiation therapy is not established. Therapies targeted against C-KIT activating mutations, identified in many mucosal melanomas, are emerging as promising treatments. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Emerging regulatory paradigms in glutathione metabolism

PubMed Central

Liu, Yilin; Hyde, Annastasia S.; Simpson, Melanie A.; Barycki, Joseph J.

2015-01-01

One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity, and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer, and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites, and highlight remaining questions about molecular details of the accepted regulatory modes. PMID:24974179

Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

PubMed

Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

2017-08-31

Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

[Alternative nutrition and glutathione levels].

PubMed

Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

1999-08-30

Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P < 0.01). Lactoovovegetarians because of their protein intake in adequate amounts with a 27% proportion of animal proteins (dairy products, eggs) consume a balanced mixture of amino acids, which is reflected in total protein levels similar to omnivores and significantly higher values of glutathione -5.26 +/- 0.12 mumol/g Hb, P < 0.05 (intake of glutathione in diet, higher consumption of fruit and vegetable in comparison to omnivores). A sufficient supply of glutathione as the substrate for enzymatic reactions of hydrogen peroxide or lipid hydroperoxide catabolism, as well as for detoxication of xenobiotics, was reflected in lactoovovegetarians in a significantly higher activity of glutathione-peroxidase and glutathione-S-transferase in erythrocytes. Low

Ileal Amino Acid Digestibility of Broken Rice Fed to Postweaned Piglets with or without Multicarbohydrase and Phytase Supplementation.

PubMed

Dadalt, J C; Gallardo, C; Polycarpo, G V; Budiño, F E L; Rogiewicz, A; Berto, D A; Trindade Neto, M A

2016-10-01

Most of amino acid (AA) digestibility values for feed ingredients are obtained using pigs cannulated in the distal ileum. The ileal-cannulated pig model uses pigs older than six weeks due to difficulties related to implanting the T-cannula in distal ileum of younger pigs and complications during the post-surgical recovery. However, to properly formulate the diet of weaned pigs, the nutritive value of feed ingredients should be determined with younger pigs. Thus, 25 weaned pigs were used to determine the apparent total tract digestibility (ATTD) of nutrients, energy, and apparent ileal digestibility (AID) and standardized ileal digestibility (SID) ileal AA digestibility of broken rice (BR), with or without multicarbohydrase (MC) and phytase (Phy) supplementation. Piglets were weaned at 23 d of age and individually housed in digestibility cages until 45 d of age. The trial consisted of 7 d of adaptation to the experimental diets and 3 d of excreta (feces and urine) collection. Ileal digesta was collected at slaughter (about 6 weeks of age). A completely randomized experimental design was used to determine the effects of MC and Phy. Reference diets (RD, 5% casein) was replaced by 30% of BR with or without MC, Phy, or MC+Phy. The RD was used to quantify endogenous AA losses. BR with Phy supplied had increased the ATTD of dry matter (p<0.05) and SID of histidine (p = 0.05), arginine, leucine, lysine, valine, alanine, and proline (p<0.05). BR with MC had been increased digestible energy and protein and SID for histidine (p<0.05). There was no interaction between Phy and MC on the BR nutrient digestibilities. Standardized amino acid digestibilities of BR, without enzymes, were lower than those values reported in the literature. The MC and Phy improved the digestibility of some nutrients and energy of BR in post-weaned piglet diets.

Ultrastructural basis for the efficiency of an ileal orthotopic neobladder 27 years after surgery.

PubMed

Orlandini, G; Guizzardi, S; Ferretti, S; Simonazzi, M; Bucci, G; Gatti, R

2002-01-01

The morphological and functional basis of the excellent clinical outcome of ileal orthotopic neobladders are largely unknown. Only long-term follow-up studies will provide an adequate answer to this unsettled question. We have studied a patient who underwent this type of surgery over 27 years ago. Besides an important secretive adaptation we have found, at the ultrastructural level, that the monolayered epithelium does not show signs of true metaplasia and that changes had occurred in the intercellular junctions, namely that desmosomes are significantly increased. Although limited to a single case, these features, if confirmed by further observations, suggest a working hypothesis for the understanding of the definitive phenotypic adaptation of the ileal epithelium to the new aggressive environment. Copyright 2002 S. Karger AG, Basel

Changes of reduced glutathion, glutathion reductase, and glutathione peroxidase after radiation in guinea pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erden, M.; Bor, N.M.

1984-04-01

In this series of experiments the protective action of reduced glutathion due to ionizing radiation has been studied. In the experimental group 18 guinea pigs were exposed to successive radiations of 150 rad 3 or 4 days apart. Total dose given amounted to 750 rad which is the LD50 for guinea pigs. Blood samples were taken 30 min after each exposure. The control series were sham radiated but otherwise treated identically. The cells of the removed blood samples were separated by centrifugation and were subjected to the reduced glutathion stability test. GSSGR, GPer, and LDH enzyme activities were also measuredmore » of which the latter served as a marked enzyme. It was found that LDH did not show any alteration after radiation. The reduced glutathion stability test showed a consistent but minor reduction (P greater than 0.05), in the experimental group. GSSGR enzyme activity on the other hand was reduced significantly (from 176.48 +/- 11.32 to 41.34 +/- 1.17 IU/ml of packed erythrocytes, P less than 0.001) in the same group. GPer activity showed a consistent but minor elevation during the early phase of the experimental group. It was later increased significantly beginning after 600 rad total radiation on the fourth session (P less than 0.050).« less

Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia.

PubMed

He, Yan; Yuan, Xiaoming; Zhou, Guangrong; Feng, Aiwen

2018-01-01

Insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) play a role in the maintenance of gut mucosal barrier function. Nevertheless, IGF-I/IGFBP-3 and tight junction protein (TJP) expression in small intestinal mucosa are often impaired during endotoxemia. In this model of acute endotoxemia, the regulatory effect of berberine on IGF-I/IGFBP-3 and TJP expression in ileal mucosa was evaluated. The findings revealed systemic injection of lipopolysaccharide (LPS) suppressed mRNA and protein expression of IGF-I and IGFBP-3, but berberine ameliorated their production. LPS injection inhibited occludin and claudin-1 protein generation, and this inhibitory effect of LPS was abolished by berberine. Inhibition of IGF-I/IGFBP-3 signaling by AG1024 or siRNAs reduced berberine-induced occludin and claudin-1 production. Additionally, GW9662 was found to repress berberine-induced IGF-I/IGFBP-3 expression, indicating of a cross-link between PPARγ and IGF-I/IGFBP-3 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Bile acid malabsorption after continent urinary diversion with an ileal reservoir.

PubMed

Olofsson, G; Fjälling, M; Kilander, A; Ung, K A; Jonsson, O

1998-09-01

We determine the effect of urinary diversion with a Kock ileal reservoir on bile acid absorption and bowel habits. We asked 96 patients with a Kock ileal urinary reservoir to record bowel habits and abdominal symptoms for 1 week. Data on 75 patients were further analyzed. Bile acid absorption was determined in 29 healthy control subjects, in 17 before and 6 months after continent urinary diversion, and in 21, 2 to 14 years postoperatively. Bile acid absorption was considered pathological when retention of less than 10% of an oral capsule containing selenium-75 labeled tauroselcholic acid (SeHCAT) was noted after 1 week. Mean number of defecations plus or minus standard deviation was 9.4 +/- 6.1 (75 cases). Of the patients 13% had 15 or more stools per week and 15% complained of always having loose stools. Mean value for the SeHCAT test was 32 +/- 19% preoperatively and 17 +/- 16% 6 months postoperatively (p = 0.0023). The corresponding value for healthy controls was 39 +/- 18%. Significant relationships were found between the results of the SeHCAT test postoperatively, and the number of stools per week and consistency of the feces. All patients with more than 10 defecations per week had a pathological SeHCAT test. Most patients with an ileal urinary reservoir have fairly normal bowel habits. Bile acid absorption is significantly reduced postoperatively and approximately a third of the patients have a pathological SeHCAT test. Preoperative investigation of bowel habits is recommended and a SeHCAT test should be performed in patients with frequent, loose defecations. Other types of diversion should be offered when preoperative retention is below 10 to 20% especially in patients with impaired anal control.

Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana

PubMed Central

Koffler, Barbara Eva; Maier, Romana; Zechmann, Bernd

2011-01-01

Abstract Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and γ-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in γ-glutamylcysteine (γ-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of γ-glutamylcysteine synthetase (GSH1) – the first enzyme of glutathione synthesis – causes a reduction of γ-EC levels and an accumulation of all other glutathione precursors within the cells. PMID:22050910

Salmonella induces prominent gene expression in the rat colon

PubMed Central

Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Roosing, Susanne; Vink, Carolien; Katan, Martijn B; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg MJ

2007-01-01

Background Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. Results Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFNγ and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. Conclusion We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression

Salmonella induces prominent gene expression in the rat colon.

PubMed

Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Roosing, Susanne; Vink, Carolien; Katan, Martijn B; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2007-09-12

Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFN gamma and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression.

Laparoscopic management of terminal ileal volvulus caused by Meckel's diverticulum.

PubMed

Xanthis, A; Hakeem, A; Safranek, P

2015-04-01

Complications from a Meckel's diverticulum include diverticulitis, bleeding, intussusception, bowel obstruction, a volvulus, a vesicodiverticular fistula, perforation or very rarely as a tumour. We report a case where a Meckel's diverticulum presented with a terminal ileal volvulus in a 32-year-old man without the presence of a typical vitelline band or axial torsion of the diverticulum causing the volvulus. It was successfully managed laparoscopically.

Glutathione-related enzymes and the eye.

PubMed

Ganea, Elena; Harding, John J

2006-01-01

Glutathione and the related enzymes belong to the defence system protecting the eye against chemical and oxidative stress. This review focuses on GSH and two key enzymes, glutathione reductase and glucose-6-phosphate dehydrogenase in lens, cornea, and retina. Lens contains a high concentration of reduced glutathione, which maintains the thiol groups in the reduced form. These contribute to lens complete transparency as well as to the transparent and refractive properties of the mammalian cornea, which are essential for proper image formation on the retina. In cornea, gluthatione also plays an important role in maintaining normal hydration level, and in protecting cellular membrane integrity. In retina, glutathione is distributed in the different types of retinal cells. Intracellular enzyme, glutathione reductase, involved in reducing the oxidized glutathione has been found at highest activity in human and primate lenses, as compared to other species. Besides the enzymes directly involved in maintaining the normal redox status of the cell, glucose-6-phosphate dehydrogenase which catalyzes the first reaction of the pentose phosphate pathway, plays a key role in protection of the eye against reactive oxygen species. Cornea has a high activity of the pentose phosphate pathway and glucose-6-phosphate dehydrogenase activity. Glycation, the non-enzymic reaction between a free amino group in proteins and a reducing sugar, slowly inactivates gluthathione-related and other enzymes. In addition, glutathione can be also glycated. The presence of glutathione, and of the related enzymes has been also reported in other parts of the eye, such as ciliary body and trabecular meshwork, suggesting that the same enzyme systems are present in all tissues of the eye to generate NADPH and to maintain gluthatione in the reduced form. Changes of glutathione and related enzymes activity in lens, cornea, retina and other eye tissues, occur with ageing, cataract, diabetes, irradiation and

Magnetic Resonance Imaging Predicts Histopathological Composition of Ileal Crohn's Disease.

PubMed

Wagner, Mathilde; Ko, Huaibin Mabel; Chatterji, Manjil; Besa, Cecilia; Torres, Joana; Zhang, Xiaofei; Panchal, Hinaben; Hectors, Stefanie; Cho, Judy; Colombel, Jean-Frederic; Harpaz, Noam; Taouli, Bachir

2018-05-25

Recently, smooth muscle hypertrophy has been suggested to be a contributor to small bowel lesions secondary to Crohn's disease [CD], in addition to inflammation and fibrosis. Here, we assess the value of magnetic resonance imaging [MRI] for the characterisation of histopathological tissue composition of small bowel CD, including inflammation, fibrosis, and smooth muscle hypertrophy. A total of 35 consecutive patients [male/female 17/18, mean age 33 years] with ileal CD, who underwent small bowel resection and a preoperative contrast-enhanced MRI examination within 1 month before surgery, were retrospectively included. Image assessment included qualitative [pattern/degree of enhancement, presence of ulcerations/fistulas/abscesses] and quantitative parameters [wall thickness on T2/T1-weighted images [WI], enhancement ratios, apparent diffusion coefficient [ADC], Clermont and Magnetic Resonance Index of Activity [MaRIA] scores). MRI parameters were compared with histopathological findings including active inflammation, collagen deposition, and muscle hypertrophy using chi square/Fisher or Mann-Whitney tests and univariate/multivariate logistic/linear regression analyses. Forty ileal segments were analysed in 35 patients. Layered pattern at early-post-contrast phase was more prevalent (odds ratio [OR] = 8; p = 0.008), ADC was significantly lower [OR = 0.005; p = 0.022], and MaRIA score was significantly higher [OR = 1.125; p = 0.022] in inflammation grades 2-3 compared with grade 1. Wall thickness on T2WI was significantly increased [OR = 1.688; p = 0.043], and fistulas [OR = 14.5; p = 0.017] were more prevalent in segments with disproportionately increased muscle hypertrophy versus those with disproportionately increased fibrosis. MaRIA/Clermont scores, wall thickness on T1WI and T2WI, and ADC were all significantly correlated with degree of muscular hypertrophy. MRI predicts the degree of inflammation, and can distinguish prominent muscle hypertrophy from prominent

Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats.

PubMed

Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y; Owyang, Chung

2014-02-01

Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction (PCR) and 454 pyrosequencing were used to analyze bacterial 16S ribosomal RNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

PubMed Central

Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung

2014-01-01

Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699

A diet containing whey protein, glutamine, and TGFbeta modulates gut protein metabolism during chemotherapy-induced mucositis in rats.

PubMed

Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Le Pessot, Florence; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

2010-08-01

Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect (CP), which contains whey proteins, TGFbeta-rich casein, and free glutamine, on mucositis in rats. Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days -7 to 9. In the placebo diet, whey proteins and TGFbeta-rich casein were replaced by TGFbeta-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean +/- SEM, were compared using two-way ANOVA. At day 3, villus height was markedly decreased in the placebo (296 +/- 11 microm) and CP groups (360 +/- 10 microm) compared with controls (464 +/- 27 microm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 +/- 0.2 vs. 1.7 +/- 0.2 micromol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 +/- 4.9%/day) compared with controls (121.5 +/- 12.1, P < 0.05), but not in the CP group (106.0 +/- 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

Glutathione synthetase deficiency: a family report.

PubMed Central

Pejaver, R K; Watson, A H

1994-01-01

Glutathione synthetase deficiency is a rare inborn error of metabolism. Low levels of and at times unstable molecules of glutathione synthetase leads to glutathione deficiency affecting various systems of the body. The inheritance is thought to be of autosomal recessive variety. We diagnosed the condition in a neonate and proceeded to investigate the family. The results are discussed below. PMID:8158601

High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon.

PubMed

Lan, Annaïg; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Véronique; Desclée de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tomé, Daniel; Blachier, François

2015-01-01

We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Biochemical heterogeneity in glutathione synthetase deficiency.

PubMed Central

Spielberg, S P; Garrick, M D; Corash, L M; Butler, J D; Tietze, F; Rogers, L; Schulman, J D

1978-01-01

Two different clinical syndromes are associated with glutathione synthetase deficiency, one presenting with hemolytic anemia and 5-oxoprolinuria, the other with isolated hemolysis. We have differentiated these disorders on an enzymatic basis. In 5-oxoprolinuria, all cell types examined have grossly deficient enzyme activity and glutathione content. In contrast, in the nonoxoprolinuric variant, erythrocytes have decreased enzyme activity and glutathione content, whereas nucleated cells maintain substantial levels of both. The enzyme in this disorder is unstable in vitro and has shortened survival in intact erythrocytes. Nucleated cells appear able to maintain sufficient enzyme activity and concentrations of glutathione to suppress overproduction of 5-oxoproline. PMID:659603

Measurement of true ileal calcium digestibility in meat and bone meal for broiler chickens using the direct method.

PubMed

Anwar, M N; Ravindran, V; Morel, P C H; Ravindran, G; Cowieson, A J

2016-01-01

The objective of the study that is presented herein was to determine the true ileal calcium (Ca) digestibility in meat and bone meal (MBM) for broiler chickens using the direct method. Four MBM samples (coded as MBM-1, MBM-2, MBM-3 and MBM-4) were obtained and analyzed for nutrient composition, particle size distribution and bone to soft tissue ratio. The Ca concentrations of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 71, 118, 114 and 81 g/kg, respectively. The corresponding geometric mean particle diameters and bone to soft tissue ratios were 0.866, 0.622, 0.875 and 0.781 mm, and 1:1.49, 1:0.98, 1:0.92 and 1:1.35, respectively. Five experimental diets, including four diets with similar Ca concentration (8.3 g/kg) from each MBM and a Ca and phosphorus-free diet, were developed. Meat and bone meal served as the sole source of Ca in the MBM diets. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to six replicate cages (eight birds per cage) and offered from d 28 to 31 post-hatch. Apparent ileal Ca digestibility was calculated by the indicator method and corrected for ileal endogenous Ca losses to determine the true ileal Ca digestibility. Ileal endogenous Ca losses were determined to be 88 mg/kg dry matter intake. True ileal Ca digestibility coefficients of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 0.560, 0.446, 0.517 and 0.413, respectively. True Ca digestibility of MBM-1 was higher (P < 0.05) than MBM-2 and MBM-4 but similar (P > 0.05) to that of MBM-3. True Ca digestibility of MBM-2 was similar (P > 0.05) to MBM-3 and MBM-4, while that of MBM-3 was higher (P < 0.05) than MBM-4. These results demonstrated that the direct method can be used for the determination of true Ca digestibility in feed ingredients and that Ca in MBM is not highly available as often assumed. The variability in true Ca digestibility of MBM samples could not be attributed to Ca content, percentage

Methylmercury alters glutathione homeostasis by inhibiting glutaredoxin 1 and enhancing glutathione biosynthesis in cultured human astrocytoma cells.

PubMed

Robitaille, Stephan; Mailloux, Ryan J; Chan, Hing Man

2016-08-10

Methylmercury (MeHg) is a neurotoxin that binds strongly to thiol residues on protein and low molecular weight molecules like reduced glutathione (GSH). The mechanism of its effects on GSH homeostasis particularly at environmentally relevant low doses is not fully known. We hypothesized that exposure to MeHg would lead to a depletion of reduced glutathione (GSH) and an accumulation of glutathione disulfide (GSSG) leading to alterations in S-glutathionylation of proteins. Our results showed exposure to low concentrations of MeHg (1μM) did not significantly alter GSH levels but increased GSSG levels by ∼12-fold. This effect was associated with a significant increase in total cellular glutathione content and a decrease in GSH/GSSG. Immunoblot analyses revealed that proteins involved in glutathione synthesis were upregulated accounting for the increase in cellular glutathione. This was associated an increase in cellular Nrf2 protein levels which is required to induce the expression of antioxidant genes in response to cellular stress. Intriguingly, we noted that a key enzyme involved in reversing protein S-glutathionylation and maintaining glutathione homeostasis, glutaredoxin-1 (Grx1), was inhibited by ∼50%. MeHg treatment also increased the S-glutathionylation of a high molecular weight protein. This observation is consistent with the inhibition of Grx1 and elevated H2O2 production however; contrary to our original hypothesis we found few S-glutathionylated proteins in the astrocytoma cells. Collectively, MeHg affects multiple arms of glutathione homeostasis ranging from pool management to protein S-glutathionylation and Grx1 activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Internal versus external ureteric stents for uretero-ileal anastomosis after laparoscopic radical cystectomy with orthotopic neobladder: A prospective comparative study.

PubMed

Abdel Hakim, Mahmoud A; Abdalla, Ahmed A; Saad, Ismail R; ElSheemy, Mohammed S; El Feel, Ahmed S; Salem, Hosni K; Abdel Hakim, Amr M

2016-06-01

To prospectively compare the use of external ureteric stents with internal JJ stenting of the uretero-ileal anastomosis in patients undergoing laparoscopic radical cystectomy (LRC) with a Y-shaped ileal orthotopic neobladder (ON). The study included 69 patients undergoing LRC with ON. Patients were grouped according to the type of uretero-ileal stents used. An external ureteric stent was used in Group A (33 patients) and a JJ stent was used in Group B (36). We prospectively compared the duration of hospital stay, the incidence of short- and intermediate-term complications in the two study groups. The mean (SD) follow-up periods were 29.18 (3.94) and 28.19 (3.37) months for patients in Groups A and B, respectively. Perioperative patient characteristics were comparable in the two study groups. The use of JJ stenting was associated with a shorter hospital stay compared with external stenting, at a mean (SD) of 14.63 (3.74) and 6.8 (3.03) days in Groups A and B, respectively (P < 0.001). The incidence of urinary leakage was comparable in the two study groups, at 6.1% in Group A vs 8.3% in Group B (P = 1.0). Strictures of the uretero-ileal anastomosis occurred in two patients (6%) in Group A and confirmed by intravenous urography. All strictures were treated with antegrade JJ fixation. JJ stents could be used as an effective alternative to external ureteric stents to support the uretero-ileal anastomosis. JJ stenting is associated with a shorter hospital stay and similar complication rates compared with external stenting in patients undergoing LRC with ON.

Glutathione synthesis is essential for pollen germination in vitro

PubMed Central

2011-01-01

Background The antioxidant glutathione fulfills many important roles during plant development, growth and defense in the sporophyte, however the role of this important molecule in the gametophyte generation is largely unclear. Bioinformatic data indicate that critical control enzymes are negligibly transcribed in pollen and sperm cells. Therefore, we decided to investigate the role of glutathione synthesis for pollen germination in vitro in Arabidopsis thaliana accession Col-0 and in the glutathione deficient mutant pad2-1 and link it with glutathione status on the subcellular level. Results The depletion of glutathione by buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, reduced pollen germination rates to 2-5% compared to 71% germination in wildtype controls. The application of reduced glutathione (GSH), together with BSO, restored pollen germination and glutathione contents to control values, demonstrating that inhibition of glutathione synthesis is responsible for the decrease of pollen germination in vitro. The addition of indole-3-acetic acid (IAA) to media containing BSO restored pollen germination to control values, which demonstrated that glutathione depletion in pollen grains triggered disturbances in auxin metabolism which led to inhibition of pollen germination. Conclusions This study demonstrates that glutathione synthesis is essential for pollen germination in vitro and that glutathione depletion and auxin metabolism are linked in pollen germination and early elongation of the pollen tube, as IAA addition rescues glutathione deficient pollen. PMID:21439079

21 CFR 862.1365 - Glutathione test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

....1365 Glutathione test system. (a) Identification. A glutathione test system is a device intended to measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red blood... I (general controls). The device is exempt from the premarket notification procedures in subpart E...

21 CFR 862.1365 - Glutathione test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

....1365 Glutathione test system. (a) Identification. A glutathione test system is a device intended to measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red blood... I (general controls). The device is exempt from the premarket notification procedures in subpart E...

21 CFR 862.1365 - Glutathione test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

....1365 Glutathione test system. (a) Identification. A glutathione test system is a device intended to measure glutathione (the tripeptide of glycine, cysteine, and glutamic acid) in erythrocytes (red blood... I (general controls). The device is exempt from the premarket notification procedures in subpart E...

Mucosal Vaccine Development Based on Liposome Technology

PubMed Central

Norling, Karin; Bally, Marta; Höök, Fredrik

2016-01-01

Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

Hydroalcoholic extract of Carum carvi L. in oral mucositis: a clinical trial in male golden hamsters.

PubMed

Mardani, M; Afra, S M; Tanideh, N; Tadbir, A Andisheh; Modarresi, F; Koohi-Hosseinabadi, O; Iraji, A; Sepehrimanesh, M

2016-01-01

Several studies have attempted to prevent or improve oral mucositis (OM) but have not produced a qualified treatment yet. This study evaluates the effects of Carum carvi L. (caraway) hydroalcoholic extract (CHE) as one of the traditional medicinal plants in 5-fluorouracil (5-FU)-induced OM in golden hamsters. OM was induced in 54 male golden hamsters by 5-FU and cheek pouch scratching. Starting from day 12, 500 and 1000 mg kg(-1) per day topical CHE were administered. Pouch histopathology score, malondialdehyde and reduced glutathione contents, and activity of myeloperoxidase plus microbial cultures of cheek pouch, antimicrobial properties of CHE, and essential oil constituents were evaluated. Lower histopathology score (0, 1, and 2) and malondialdehyde level, higher reduced glutathione level and activities of myeloperoxidase were detected in 1000 and 500 mg kg(-1) per day topical CHE and control groups, respectively (P < 0.001). The CHE was more potent against Staphylococcus epidermidis and Streptococcus intermedius. γ-Terpinene (37.2%) was identified as the main constituent of essential oil. The use of CHE in topical form may be associated with reduced intensity of OM. This may be due to appropriate antibacterial activity and terpinene contents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of mucosal loading on vocal fold vibration

NASA Astrophysics Data System (ADS)

Tao, Chao; Jiang, Jack J.

2009-06-01

A chain model was proposed in this study to examine the effects of mucosal loading on vocal fold vibration. Mucosal loading was defined as the loading caused by the interaction between the vocal folds and the surrounding tissue. In the proposed model, the vocal folds and the surrounding tissue were represented by a series of oscillators connected by a coupling spring. The lumped masses, springs, and dampers of the oscillators modeled the tissue properties of mass, stiffness, and viscosity, respectively. The coupling spring exemplified the tissue interactions. By numerically solving this chain model, the effects of mucosal loading on the phonation threshold pressure, phonation instability pressure, and energy distribution in a voice production system were studied. It was found that when mucosal loading is small, phonation threshold pressure increases with the damping constant Rr, the mass constant Rm, and the coupling constant Rμ of mucosal loading but decreases with the stiffness constant Rk. Phonation instability pressure is also related to mucosal loading. It was found that phonation instability pressure increases with the coupling constant Rμ but decreases with the stiffness constant Rk of mucosal loading. Therefore, it was concluded that mucosal loading directly affects voice production.

Effects of high ambient temperature on the community structure and composition of ileal microbiome of broilers.

PubMed

Wang, X J; Feng, J H; Zhang, M H; Li, X M; Ma, D D; Chang, S S

2018-06-01

The intestinal microbiome has been shown to influence animal nutrient metabolism and immune homeostasis. The present study aimed to examine the effect of heat stress on the intestinal microbiome of broilers using pyrosequencing technologies. Ninety-six Arbor Acres broiler chicks were allocated to thermoneutral control (TC; 21 ± 1°C) and high ambient temperature (HT; 31 ± 1°C) groups (6 cages of 8 birds per group), respectively, and raised in 2 controlled climate chambers from 28 to 42 d old. Genomic DNA was extracted from ileal contents isolated from 6 male broiler chicks of each group at 42 d old, and then amplified based on the V3-4 hyper-variable region of 16S rRNA. High temperature had no significant effects, but tended to influence the relative abundance of major phyla and orders in the broilers' ileal microbiota. Analysis of linear effect size feature selection identified 9 discriminative features (genus level, linear discriminant analysis score > 3). Clostridium XIVb, Streptophyta, Faecalibacterium, Rothia, Alistipes, Azospirillum, and Oscillibacter were enriched, while Coprococcus and Streptococcus were reduced in heat-stressed broilers. High temperature significantly influenced the alpha diversity, with higher observed species (P = 0.004), whole-tree phylogenetic diversity (P = 0.002), and Chao 1 (P = 0.002), but the Pielou, Shannon, and Simpson indices were unaltered (P > 0.05), indicating that high temperature increased the ileal microbiota species richness. Based on unweighted UniFrac distance metric matrices, principal component analysis showed that the HT group formed a distinct cluster clearly set apart from the TC group. Analysis of similarity also indicated that samples within groups were more similar to each other than to any samples from other groups (R = 0.626; P = 0.004). In conclusion, high temperature influenced the bacterial composition and community structure of the ileal microbiota of broilers, specifically by increasing the species

Atraumatic splenic rupture and ileal volvulus following cocaine abuse.

PubMed

Ballard, David H; Smith, J Patrick; Samra, Navdeep S

2015-01-01

We present the case of a 38-year-old male with an atraumatic splenic rupture, hemoperitoneum, and ileal volvulus following acute cocaine intoxication. Computed tomography showed a "whirl sign", a subcapsular splenic hematoma with suspected peripheral laceration, and diffuse hemoperitoneum. At laparotomy, the spleen was confirmed to be the source of bleeding and was removed. A nonreducible volvulus was found at the distal ileum, and this segment of small bowel was removed. The patient had an uneventful postoperative recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of glutathione and glutathione disulfide in biological samples: an in-depth review.

PubMed

Monostori, Péter; Wittmann, Gyula; Karg, Eszter; Túri, Sándor

2009-10-15

Glutathione (GSH) is a thiol-containing tripeptide, which plays central roles in the defence against oxidative damage and in signaling pathways. Upon oxidation, GSH is transformed to glutathione disulfide (GSSG). The concentrations of GSH and GSSG and their molar ratio are indicators of cell functionality and oxidative stress. Assessment of redox homeostasis in various clinical states and medical applications for restoration of the glutathione status are of growing importance. This review is intended to provide a state-of-the-art overview of issues relating to sample pretreatment and choices for the separation and detection of GSH and GSSG. High-performance liquid chromatography, capillary electrophoresis and gas chromatography (as techniques with a separation step) with photometric, fluorimetric, electrochemical and mass spectrometric detection are discussed, stress being laid on novel approaches.

p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates.

PubMed

Klos, C; Koob, M; Kramer, C; Dekant, W

1992-07-01

p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.

Characteristics of lipid substances activating the ileal brake in the rat.

PubMed Central

Brown, N J; Read, N W; Richardson, A; Rumsey, R D; Bogentoft, C

1990-01-01

Studies were carried out in 36 adult male rats to determine the characteristics of lipid substances which, after infusion into the ileum, slow the stomach to caecum transit time of the head of a bean meal in the rat. Stomach to caecum transit time was measured by environmental hydrogen analysis. Ileal infusion of a range of free fatty acids including petroselinic, oleic, myristoleic, erucic, linoleic, and linolenic all significantly slowed stomach to caecum transit time, as did the detergents (sodium bis (2-ethyl hexyl) sulphosuccinate and sodium linoleyl sulphate), the triglyceride corn oil, and the phospholipid lecithin. Although the lipid soluble deconjugated bile acid deoxycholic acid slowed stomach to caecum transit time, the water soluble conjugated bile acid taurocholic acid accelerated it. Infusion of the lipid alcohol oleyl alcohol and the calcium chelating agent disodium edetate (EDTA) into the ileum did not delay the passage of the meal through the stomach and small intestine. The diversity of lipid substances activating the ileal brake suggest a nonspecific effect by lipid soluble substances that can penetrate cell membranes. The lack of effect of EDTA suggested that calcium binding was not important. PMID:2128071

Early feed restriction of lambs modifies ileal epimural microbiota and affects immunity parameters during the fattening period.

PubMed

Frutos, J; Andrés, S; Yáñez-Ruiz, D R; Benavides, J; López, S; Santos, A; Martínez-Valladares, M; Rozada, F; Giráldez, F J

2018-04-22

Bacteria firmly attached to the gastrointestinal epithelium during the pre-weaning phase may show a significant impact on nutrient processing, immunity parameters, health and feed efficiency of lambs during post-weaning phases. Thus, the aim of this study was to describe the differences in the ileal epimural microbiota (e.g. total bacteria, Prevotella spp., Bifidobacterium spp. and Lactobacillus spp.) of fattening lambs promoted by early feed restriction during the suckling phase trying to elucidate some of the underlying mechanisms behind changes in feed efficiency during the fattening period. A total of 24 Merino lambs (average BW 4.81±0.256 kg) were used, 12 of them (ad libitum, ADL) kept permanently in individual pens with their mothers, whereas the other 12 lambs were separated from their dams for 9 h each day to be exposed to milk restriction (RES). After weaning (BW=15 kg) all the animals were penned individually, offered the same complete pelleted diet (35 g/kg BW per day) and slaughtered at a BW of 27 kg. During the fattening period, reduced gain : feed ratio (0.320 v. 0.261, P<0.001) was observed for the RES group. Moreover, increments of Prevotella spp. were detected in the ileal epimural microbiota of RES lambs (P<0.05). There were also higher numbers of infiltrated lymphocytes (T and B cells) in the ileal lamina propria (P<0.05), a higher M-cell labelling intensity in ileal Peyer's patches domes (P<0.05) and a trend towards a thickening of the submucosa layer when compared with the ADL group (P=0.057). Some other immunological parameters, such as an increased immunoglobulin A (IgA) production (pg IgA/µg total protein) and increments in CD45+ cells were also observed in the ileum of RES group (P<0.05), whereas transforming growth factor β and toll-like receptor gene expression was reduced (P<0.05). In conclusion, early feed restriction during the suckling phase promoted changes in ileal epimural microbiota and several immunity parameters that could

Microbiota and Mucosal Immunity in Amphibians

PubMed Central

Colombo, Bruno M.; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

2015-01-01

We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota. PMID:25821449

Pathogenesis of tropical sprue: A pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake

PubMed Central

Ghoshal, Uday C.; Kumar, Sunil; Misra, Asha; Choudhuri, Gourdas

2013-01-01

Background & objectives: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). Methods: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). Results: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m2) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. Interpretation & conclusions: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS. PMID:23481053

Effects of mucosal loading on vocal fold vibration.

PubMed

Tao, Chao; Jiang, Jack J

2009-06-01

A chain model was proposed in this study to examine the effects of mucosal loading on vocal fold vibration. Mucosal loading was defined as the loading caused by the interaction between the vocal folds and the surrounding tissue. In the proposed model, the vocal folds and the surrounding tissue were represented by a series of oscillators connected by a coupling spring. The lumped masses, springs, and dampers of the oscillators modeled the tissue properties of mass, stiffness, and viscosity, respectively. The coupling spring exemplified the tissue interactions. By numerically solving this chain model, the effects of mucosal loading on the phonation threshold pressure, phonation instability pressure, and energy distribution in a voice production system were studied. It was found that when mucosal loading is small, phonation threshold pressure increases with the damping constant R(r), the mass constant R(m), and the coupling constant R(mu) of mucosal loading but decreases with the stiffness constant R(k). Phonation instability pressure is also related to mucosal loading. It was found that phonation instability pressure increases with the coupling constant R(mu) but decreases with the stiffness constant R(k) of mucosal loading. Therefore, it was concluded that mucosal loading directly affects voice production.

Treatment of oral mucositis due to chemotherapy

PubMed Central

Bagán-Sebastián, José V

2016-01-01

Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the boolean operators “AND” and “NOT”. A total of 268 articles were obtained, of which 96 met the inclusion criteria. Results Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation. Conclusions Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis – though further studies are needed to confirm the results obtained. Key words:Chemotherapy-Induced Oral Mucositis Treatment. PMID:27034762

Plastid-Localized Glutathione Reductase2–Regulated Glutathione Redox Status Is Essential for Arabidopsis Root Apical Meristem Maintenance[C][W

PubMed Central

Yu, Xin; Pasternak, Taras; Eiblmeier, Monika; Ditengou, Franck; Kochersperger, Philip; Sun, Jiaqiang; Wang, Hui; Rennenberg, Heinz; Teale, William; Paponov, Ivan; Zhou, Wenkun; Li, Chuanyou; Li, Xugang; Palme, Klaus

2013-01-01

Glutathione is involved in thiol redox signaling and acts as a major redox buffer against reactive oxygen species, helping to maintain a reducing environment in vivo. Glutathione reductase (GR) catalyzes the reduction of glutathione disulfide (GSSG) into reduced glutathione (GSH). The Arabidopsis thaliana genome encodes two GRs: GR1 and GR2. Whereas the cytosolic/peroxisomal GR1 is not crucial for plant development, we show here that the plastid-localized GR2 is essential for root growth and root apical meristem (RAM) maintenance. We identify a GR2 mutant, miao, that displays strong inhibition of root growth and severe defects in the RAM, with GR activity being reduced to ∼50%. miao accumulates high levels of GSSG and exhibits increased glutathione oxidation. The exogenous application of GSH or the thiol-reducing agent DTT can rescue the root phenotype of miao, demonstrating that the RAM defects in miao are triggered by glutathione oxidation. Our in silico analysis of public microarray data shows that auxin and glutathione redox signaling generally act independently at the transcriptional level. We propose that glutathione redox status is essential for RAM maintenance through both auxin/PLETHORA (PLT)-dependent and auxin/PLT-independent redox signaling pathways. PMID:24249834

A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats.

PubMed

Khayyal, Mohamed T; Abdel-Naby, Doaa H; Abdel-Aziz, Heba; El-Ghazaly, Mona A

2014-09-25

Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

PubMed

Arora, Umang; Kedia, Saurabh; Garg, Prerna; Bopanna, Sawan; Jain, Saransh; Yadav, Dawesh P; Goyal, Sandeep; Gupta, Vipin; Sahni, Peush; Pal, Sujoy; Dash, Nihar Ranjan; Madhusudhan, Kumble Seetharama; Sharma, Raju; Makharia, Govind; Ahuja, Vineet

2018-06-01

The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

New generation of oral mucosal vaccines targeting dendritic cells

PubMed Central

Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

2013-01-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

Effects of corn gluten feed inclusion at graded levels in a corn-soybean diet on the ileal and fecal digestibility of growing pigs

PubMed Central

2014-01-01

Background This study aimed to determine the effect of the inclusion of corn gluten feed (CGF) on the apparent and standardized ileal digestibility of protein and amino acids and the apparent ileal and total tract digestibility of energy in growing pigs. The study was performed using 16 barrows (weight, 45.3 ± 4.5 kg) that were fitted with a T cannula at the terminal ileum. There were four treatments: a corn-soybean diet without CGF and three corn-soybean diets containing increasing levels of CGF (65, 130, and 195 g/kg). Data were analyzed according to a randomized complete block design, four blocks with four pigs each (one pig per treatment). The trend of the response (linear or quadratic) was determined using orthogonal contrasts, and when a linear effect was determined, a linear equation was obtained. Results The results showed that the inclusion up to 195 g/kg of CGF in the corn-soybean diet did not diminish the ileal digestibility (apparent and standardized) of protein and amino acids (P > 0.05), except that of phenylalanine, cystine, and proline. A linear decrease (P < 0.05) per gram of CGF added to the diet in the apparent and standardized ileal digestibility of phenylalanine (0.011 and 0.015 percentage units, respectively), cystine (0.048 and 0.043 percentage units, respectively), and proline (0.045 and 0.047 percentage units, respectively) was noted. Similarly, ileal digestibility of dry matter and energy were adversely affected (reduced by 0.028 and 0.025 percentage units, respectively, per gram of CGF increment in the diet). A significant (P < 0.05) linear reduction in total tract digestibility with increase in CGF amount in the diet was observed for energy (0.027 percentage units), dry matter (0.027 percentage units), crude protein (0.020 percentage units), and neutral detergent fiber (0.041 percentage units) per gram of CGF added to the diet. Conclusion CGF did not affect the ileal digestibility of protein and most amino acids but

A case report of modified laparoscopic keyhole plus repair for parastomal hernia following ileal conduit

PubMed Central

Rajapandian, S.; Jankar, Samrat V.; Dey, Sumanta; Annamaneni, Vikram; Sabnis, Sandeep C.; Sathiymurthy, S.; Parthsarathi, R.; Raj, P. Praveen; Senthilnathan, P.; Palanivelu, C.

2017-01-01

Parastomal hernia is one of the most common but challenging complication after stoma formation. Modified Sugarbaker technique is the recommended procedure for repair parastomal hernia, however, keyhole repair technique had also been used in certain instances. In cases of parastomal hernia following ileal conduit procedure, the Sugarbaker technique is been described, although with associated theoretical risk of conduit failure. We are reporting a case of post-radical cystectomy with ileal conduit presented with symptomatic large parastomal hernia. Laparoscopic modified keyhole plus repair has been done successfully in this patient with no recurrence in 2 years of follow-up. The purpose of our case report is to describe our novel modification of the laparoscopic keyhole technique which can be a feasible and acceptable alternative surgical method in these types of patients. PMID:28695881

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Mucosal melanomas in the racially diverse population of California.

PubMed

Altieri, Lisa; Wong, Michael K; Peng, David H; Cockburn, Myles

2017-02-01

Mucosal melanomas are rare, poorly understood neoplasms without a consensus standard of care. We sought to define mucosal melanoma tumor characteristics and the racial/ethnic attributes of patients with mucosal melanomas. We analyzed 130,920 cutaneous melanomas and 1919 mucosal melanomas recorded in the population-based California Cancer Registry from 1988 to 2013. Although only 1% of melanomas occurring in nonHispanic whites were mucosal, other racial/ethnic groups had a higher proportion of mucosal melanomas (15% for Asian/Pacific Islanders, 9% for nonHispanic blacks, and 4% for Hispanics). Anorectal mucosal melanomas were most common in female Asian/Pacific Islanders, whereas genitourinary mucosal melanomas were highest in nonHispanic whites, and head and neck tumors were most common among Hispanics. Stage at presentation was not uniform among racial/ethnic groups, with Asian/Pacific Islanders having the highest rates of metastasis. The lack of a standardized staging system for mucosal melanomas confounds classification and knowledge regarding metastasis. Small sample size limits comparative analysis across race, stage, site, and depth. Mucosal melanomas differ by race/ethnicity with regard to anatomic site, stage, and depth. Because early detection offers the best chance of increased survival, greater awareness will aid clinicians who care for patients at risk for these aggressive tumors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Glutathione-Enhancing Agents Protect against Steatohepatitis in a Dietary Model

PubMed Central

Im, Hee-Jeong; Chen, Theresa S.; de Villiers, Willem J. S.; McClain, Craig J.

2010-01-01

Nonalcoholic fatty liver (NAFL) and steatohepatitis (NASH) may accompany obesity, diabetes, parenteral nutrition, jejeuno-ileal bypass, and chronic inflammatory bowel disease. Currently there is no FDA approved and effective therapy available. We investigated the potential efficacy of those agents that stimulate glutathione (GSH) biosynthesis on the development of experimental steatohepatitis. Rats fed (ad libitum) amino acid based methionine-choline deficient (MCD) diet were further gavaged with (1) vehicle (MCD), (2) S-adenosylmethionine (SAMe), or (3) 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA). Results: MCD diet significantly reduced hematocrit, and this abnormality improved in the treated groups (p < 0.01). Serum transaminases were considerably elevated (AST: 5.8-fold; ALT: 3.22-fold) in MCD rats. However, administration of GSH-enhancing agents significantly suppressed these abnormal enzyme activities. MCD rats developed severe liver pathology manifested by fatty degeneration, inflammation, and necrosis, which significantly improved with therapy. Blood levels of GSH were significantly depleted in MCD rats but normalized in the treated groups. Finally, RT-PCR measurements showed a significant upregulation of genes involved in tissue remodeling and fibrosis (matrix metalloproteinases, collagen-α1), suppressor of cytokines signaling1, and the inflammatory cytokines (IL-1β, IL-6, TNF-α, and TGF-β) in the livers of rats fed MCD. GSH-enhancing therapies significantly attenuated the expression of deleterious proinflammatory and fibrogenic genes in this dietary model. This is the first report that oral administration of SAMe and PTCA provide protection against liver injury in this model and suggests therapeutic applications of these compounds in NASH patients. PMID:16498637

New generation of oral mucosal vaccines targeting dendritic cells.

PubMed

Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

2013-12-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oral Mucositis: Melatonin Gel an Effective New Treatment

PubMed Central

Abdel Moneim, Ahmed Esmat; Guerra-Librero, Ana; Florido, Javier; Shen, Ying-Qiang; Fernández-Gil, Beatriz; Acuña-Castroviejo, Darío; Escames, Germaine

2017-01-01

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, the role of melatonin in the treatment of mucositis has recently been investigated, and offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives. PMID:28481279

Effect of glutathione on phytochelatin synthesis in tomato cells.

PubMed

Mendum, M L; Gupta, S C; Goldsbrough, P B

1990-06-01

Growth of cell suspension cultures of tomato, Lycopersicon esculentum Mill. cv VFNT-Cherry, in the presence of cadmium is inhibited by buthionine sulfoximine, an inhibitor of glutathione synthesis. Cell growth and phytochelatin synthesis are restored to cells treated with buthionine sulfoximine by the addition of glutathione to the medium. Glutathione stimulates the accumulation of phytochelatins in cadmium treated cells, indicating that availability of glutathione can limit synthesis of these peptides. Exogenous glutathione causes a disproportionate increase in the level of smaller phytochelatins, notably [gamma-Glu-Cys](2)-Gly. In the presence of buthionine sulfoximine and glutathione, phytochelatins that are produced upon exposure to cadmium incorporate little [(35)S]cysteine, indicating that these peptides are probably not synthesized by sequential addition of cysteine and glutamate to glutathione.

Melatonin and nitric oxide modulate glutathione content and glutathione reductase activity in sunflower seedling cotyledons accompanying salt stress.

PubMed

Kaur, Harmeet; Bhatla, Satish C

2016-09-30

The present findings demonstrate significant modulation of total glutathione content, reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, GSH/GSSG ratio and glutathione reductase (GR; EC 1.6.4.2) activity in dark-grown seedling cotyledons in response to salt-stress (120 mM NaCl) in sunflower (Helianthus annuus L.) seedlings. A differential spatial distribution of GR activity (monitored by confocal laser scanning microscopic (CLSM) imaging) is also evident. Melatonin and nitric oxide (NO) differentially ameliorate salt stress effect by modulating GR activity and GSH content in seedling cotyledons. Total glutathione content (GSH + GSSG) exhibit a seedling age-dependent increase in the cotyledons, more so in salt-stressed conditions and when subjected to melatonin treatment. Seedlings raised in presence of 15 μM of melatonin exhibit significant increase in GR activity in cotyledon homogenates (10,000 g supernatant) coinciding with significant increase in GSH content. GSSG content and GSH/GSSG ratio also increased due to melatonin treatment. A correlation is thus evident in NaCl-sensitized modulation of GSH content and GR activity by melatonin. GSH content is down regulated by NO provided as 250 μM of sodium nitroprusside (SNP) although total glutathione content remained in similar range. A reversal of response (enhanced total glutathione accumulation) by NO scavenger (cPTIO) highlights the critical role of NO in modulating glutathione homeostasis. SNP lowers the activity of hydroxyindole-O-methyltransferase (HIOMT) - a regulatory enzyme in melatonin biosynthesis in control seedlings whereas its activity is upregulated in salt-stressed seedling cotyledons. Melatonin content of seedling cotyledons is also modulated by NO. NO and melatonin thus seem to modulate GR activity and GSH content during seedling growth under salt stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Shigella sonnei Vaccine Candidates WRSs2 and WRSs3 Are as Immunogenic as WRSS1, a Clinically Tested Vaccine Candidate, in a Primate Model of Infection

DTIC Science & Technology

2011-01-01

Experiments in rabbit ileal loops and in rhesus monkeys have shown that shigellae are initially taken up by antigen sampling microfold (M) cells that are...2011) – Table 1 Shigella antigen-specific immune responses and colonization in rhesus monkeys after nasogastric administration of WRSS1, WRSs2...the respective antigens. 3.3. Mucosal responses in rhesus monkeys The mucosal immune response to Shigella LPS, and Invaplex- 50 antigens are summarized

Laparoscopic Repair of Ileal Conduit Parastomal Hernia Using the Sling Technique

PubMed Central

Chand, Bipan

2008-01-01

Laparoscopic parastomal hernia repair has become a viable option to overcome the challenges that face the hernia surgeon. Multiple techniques have been described over the last 5 years, one of which is the lateralizing “sling” technique, first described by Sugarbaker in1980. In this study, we report the technique and our early results with the laparoscopic modified Sugarbaker repair of parastomal hernias after ileal conduit. PMID:18435893

Mucosal and systemic adjuvant activity of alphavirus replicon particles

NASA Astrophysics Data System (ADS)

Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

2006-03-01

Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

Mucosal vaccination--an old but still vital strategy.

PubMed

Długońska, Henryka; Grzybowski, Marcin

2012-01-01

The basic premise of vaccinology is to achieve strong protective immunity against defined infectious agents by a vaccine mimicking the effects of natural primary exposure to a pathogen. Because an exposure of humans and animals to microbes occurs mostly through mucosal surfaces, targeting the mucosa seems a rational and efficient vaccination strategy. Many experimental and clinical data confirmed that mucosal immunization offers many advantages over widely used in human and veterinary medicine subcutaneous or intramuscular immunization. In the present article selected aspects regarding mucosal vaccination are discussed. The structure and function of mucosa-associated lymphoid tissue (MALT), comprised of four main mucosal compartments forming a structural and functional unity as well as pivotal cellular MALT components (dendritic and M cells) were briefly characterized. Particular attention was focused on the mode of simple but efficacious delivery of vaccine antigens to mucosal surfaces. A few trials to generate potential mucosal vaccines against toxoplasmosis introduced by nasal or oral routes to experimental animals are also presented.

Glutathione Utilization by Candida albicans Requires a Functional Glutathione Degradation (DUG) Pathway and OPT7, an Unusual Member of the Oligopeptide Transporter Family

PubMed Central

Desai, Prashant Ramesh; Thakur, Anil; Ganguli, Dwaipayan; Paul, Sanjoy; Morschhäuser, Joachim; Bachhawat, Anand K.

2011-01-01

Candida albicans lacks the ability to survive within its mammalian host in the absence of endogenous glutathione biosynthesis. To examine the ability of this yeast to utilize exogenous glutathione, we exploited the organic sulfur auxotrophy of C. albicans met15Δ strains. We observed that glutathione is utilized efficiently by the alternative pathway of glutathione degradation (DUG pathway). The major oligopeptide transporters OPT1–OPT5 of C. albicans that were most similar to the known yeast glutathione transporters were not found to contribute to glutathione transport to any significant extent. A genomic library approach to identify the glutathione transporter of C. albicans yielded OPT7 as the primary glutathione transporter. Biochemical studies on OPT7 using radiolabeled GSH uptake revealed a Km of 205 μm, indicating that it was a high affinity glutathione transporter. OPT7 is unusual in several aspects. It is the most remote member to known yeast glutathione transporters, lacks the two highly conserved cysteines in the family that are known to be crucial in trafficking, and also has the ability to take up tripeptides. The transporter was regulated by sulfur sources in the medium. OPT7 orthologues were prevalent among many pathogenic yeasts and fungi and formed a distinct cluster quite remote from the Saccharomyces cerevisiae HGT1 glutathione transporter cluster. In vivo experiments using a systemic model of candidiasis failed to detect expression of OPT7 in vivo, and strains disrupted either in the degradation (dug3Δ) or transport (opt7Δ) of glutathione failed to show a defect in virulence. PMID:21994941

Factors affecting choice between ureterostomy, ileal conduit and continent reservoir after radical cystectomy: Japanese series.

PubMed

Sugihara, Toru; Yasunaga, Hideo; Horiguchi, Hiromasa; Fujimura, Tetsuya; Fushimi, Kiyohide; Yu, Changhong; Kattan, Michael W; Homma, Yukio

2014-12-01

Little is known about the disparity of choices between three urinary diversions after radical cystectomy, focusing on patient and institutional factors. We identified urothelial carcinoma patients who received radical cystectomy with cutaneous ureterostomy, ileal conduit or continent reservoir using the Japanese Diagnosis Procedure Combination database from 2007 to 2012. Data comprised age, sex, comorbidities (converted into the Charlson index), TNM classification (converted into oncological stage), hospitals' academic status, hospital volume, bed volume and geographical region. Multivariate ordinal logistic regression analyses fitted with the proportional odds model were performed to analyze factors affecting urinary diversion choices. For dependent variables, the three diversions were converted into an ordinal variable in order of complexity: cutaneous ureterostomy (reference), ileal conduit and continent reservoir. Geographical variations were also examined by multivariate logistic regression models. A total of 4790 patients (1131 cutaneous ureterostomies [23.6 %], 2970 ileal conduits [62.0 %] and 689 continent reservoirs [14.4 %]) were included. Ordinal logistic regression analyses showed that male sex, lower age, lower Charlson index, early tumor stage, higher hospital volume (≥3.4 cases/year) and larger bed volume (≥450 beds) were significantly associated with the preference of more complex urinary diversion. Significant geographical disparity was also found. Good patient condition and early oncological status, as well as institutional factors, including high hospital volume, large bed volume and specific geographical regions, are independently related to the likelihood of choosing complex diversions. Recognizing this disparity would help reinforce the need for clinical practice uniformity.

Oral mucosal lesions during orthodontic treatment.

PubMed

Baricevic, Marinka; Mravak-Stipetic, Marinka; Majstorovic, Martina; Baranovic, Marijan; Baricevic, Denis; Loncar, Bozana

2011-03-01

Oral mucosal lesions can result from irritation caused by orthodontic appliances or malocclusion, but their frequency is not known. To examine the frequency of oral mucosal lesions in wearers of orthodontic appliances in comparison to children with malocclusion. This study comprised 111 subjects: 60 wearers of orthodontic appliances and 51 controls (aged between 6 and 18 years). Type and severity of mucosal lesions, their topography, gingival inflammation, and oral hygiene status were determined by using clinical indices. Mucosal lesions were more present in wearers of orthodontic appliances than in children with malocclusion. Gingival inflammation, erosion, ulceration, and contusion were the most common findings in orthodontic patients. The severity of gingival inflammation was in correlation with oral hygiene status; the poorer oral hygiene, the more severe gingival inflammation was. Better oral hygiene status was found in children during orthodontic treatment than in children with malocclusion. Orthodontic treatment carries a higher risk of mucosal lesions and implies greater awareness of better oral hygiene as shown by the results of this study. Oral hygiene instructions and early treatment of oral lesions are important considerations in better patient's motivation, treatment planning, and successful outcome. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

GNAQ mutation in a patient with metastatic mucosal melanoma.

PubMed

Kim, Chung-Young; Kim, Dae Won; Kim, Kevin; Curry, Jonathan; Torres-Cabala, Carlos; Patel, Sapna

2014-07-16

Mucosal melanomas represent about 1% of all melanoma cases and classically have a worse prognosis than cutaneous melanomas. Due to the rarity of mucosal melanomas, only limited clinical studies with metastatic mucosal melanoma are available. Mucosal melanomas most commonly contain mutations in the gene CKIT, and treatments have been investigated using targeted therapy for this gene. Mutations in mucosal melanoma are less common than in cutaneous or uveal melanomas and occur in descending order of frequency as: CKIT (20%), NRAS (5%) or BRAF (3%). Mutations in G-alpha proteins, which are associated with activation of the mitogen-activated protein kinase pathway, have not been reported in mucosal melanomas. These G-alpha protein mutations occur in the genes GNAQ and GNA11 and are seen at a high frequency in uveal melanomas, those melanomas that begin in the eye. A 59-year old Caucasian male was diagnosed with a mucosal melanoma after evaluation for what was thought to be a hemorrhoid. Molecular analysis of the tumor revealed a GNAQ mutation. Ophthalmologic exam did not disclose a uveal melanoma. Here we report, to our knowledge, the first known case of GNAQ mutation in a patient with metastatic mucosal melanoma.

Parastomal hernias after radical cystectomy and ileal conduit diversion

PubMed Central

Donahue, Timothy F.

2016-01-01

Parastomal hernia, defined as an "incisional hernia related to an abdominal wall stoma", is a frequent complication after conduit urinary diversion that can negatively impact quality of life and present a clinically significant problem for many patients. Parastomal hernia (PH) rates may be as high as 65% and while many patients are asymptomatic, in some series up to 30% of patients require surgical intervention due to pain, leakage, ostomy appliance problems, urinary obstruction, and rarely bowel obstruction or strangulation. Local tissue repair, stoma relocation, and mesh repairs have been performed to correct PH, however, long-term results have been disappointing with recurrence rates of 30%–76% reported after these techniques. Due to high recurrence rates and the potential morbidity of PH repair, efforts have been made to prevent PH development at the time of the initial surgery. Randomized trials of circumstomal prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have shown significant reductions in PH rates with acceptably low complication profiles. We have placed prophylactic mesh at the time of ileal conduit creation in patients at high risk for PH development and found it to be safe and effective in reducing the PH rates over the short-term. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors associated with its development, and the use of prophylactic mesh placement for patients undergoing ileal conduit urinary diversion with the intent of reducing PH rates. PMID:27437533

Quantitative real-time imaging of glutathione

USDA-ARS?s Scientific Manuscript database

Glutathione plays many important roles in biological processes; however, the dynamic changes of glutathione concentrations in living cells remain largely unknown. Here, we report a reversible reaction-based fluorescent probe—designated as RealThiol (RT)—that can quantitatively monitor the real-time ...

Mucosal secretion changes during radiotherapy in the oral cavity.

PubMed

Aziz, Luaay; Ebenfelt, Anders

2007-09-01

Mucositis in the oral cavity is a serious complication during radiation therapy for head and neck cancer, causing local discomfort and pain. In severe cases, hospitalization and interruption of radiotherapy may be necessary. The pathogenesis of this mucositis is not clear. With the purpose of getting more understanding of the pathogenesis of the mucositis, we examined the mucosal secretion from ten patients during radiotherapy with an imprint technique. In the secretion we studied the cellular composition and cellular function. In eight of ten treated patients the numbers of granulocytes increased in the secretion after 2 weeks of radiation therapy. The granulocytes, however, did not show any signs of phagocytosis. The patients all developed mucositis. We propose that the granulocytes in the secretion might play an important role in the development of mucositis during radiotherapy.

GNAQ mutation in a patient with metastatic mucosal melanoma

PubMed Central

2014-01-01

Background Mucosal melanomas represent about 1% of all melanoma cases and classically have a worse prognosis than cutaneous melanomas. Due to the rarity of mucosal melanomas, only limited clinical studies with metastatic mucosal melanoma are available. Mucosal melanomas most commonly contain mutations in the gene CKIT, and treatments have been investigated using targeted therapy for this gene. Mutations in mucosal melanoma are less common than in cutaneous or uveal melanomas and occur in descending order of frequency as: CKIT (20%), NRAS (5%) or BRAF (3%). Mutations in G-alpha proteins, which are associated with activation of the mitogen-activated protein kinase pathway, have not been reported in mucosal melanomas. These G-alpha protein mutations occur in the genes GNAQ and GNA11 and are seen at a high frequency in uveal melanomas, those melanomas that begin in the eye. Case presentation A 59-year old Caucasian male was diagnosed with a mucosal melanoma after evaluation for what was thought to be a hemorrhoid. Molecular analysis of the tumor revealed a GNAQ mutation. Ophthalmologic exam did not disclose a uveal melanoma. Conclusion Here we report, to our knowledge, the first known case of GNAQ mutation in a patient with metastatic mucosal melanoma. PMID:25030020

Mucosal immunogenicity of plant lectins in mice

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

2000-01-01

The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

The mucosal immune system: From dentistry to vaccine development

PubMed Central

KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

2015-01-01

The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interconnected inductive and effector sites. Intestinal Peyer’s patches (PPs) are an inductive site containing antigen-sampling M cells and immunocompetent cells required to initiate antigen-specific immune responses. At effector sites, PP-originated antigen-specific IgA B cells become plasma cells to produce polymeric IgA and form secretory IgA by binding to poly-Ig receptor expressed on epithelial cells for protective immunity. The development of new-generation mucosal vaccines, including the rice-based oral vaccine MucoRice, on the basis of the coordinated mucosal immune system is a promising strategy for the control of mucosal infectious diseases. PMID:26460320

[Intrarenal Bacillus Calmette-Guerin perfusion therapy was effective for carcinoma in situ of the upper urinary tract after ileal conduit replacement : a case report].

PubMed

Hayashi, Takuji; Yamanaka, Yohei; Kinjo, Takanori; Katayama, Kinzo; Kamoto, Akihito; Mori, Naoki; Yoshioka, Toshiaki

2014-04-01

A 63-year-old man who had undergone radical cystectomy and ileal conduit formation for invasive bladder cancer 3 years before presented with continuous positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette-Guérin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in 100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of another catheter was effective for continuing the therapy. Urinary cytology in the left upper urinary tract and the ileal conduit became negative after the therapy. There was no evidence of recurrence or metastasis of urothelial carcinoma 6 months after the therapy.

Oral mucositis: etiology, and clinical and pharmaceutical management.

PubMed

Zur, Eyal

2012-01-01

Oral mucosal damage is one of the common and worst side effects of radiotherapy and chemotherapy treatment for cancer. With prevalence between 10% and 100%, depending on the cytotoxic and/or radiotherapy regimen and patient-associated variables, this morbid condition represents a significant problem in oncology. This article addresses oral mucositis and discusses its prevalence, risk factors, clinical and economical impacts, etiology, and clinical management in view of the most recent evidence. Despite clear progress and the development of clinical guidelines on this topic, what we currently have to offer to patients to manage mucositis and oropharyngeal pain is still inadequate. This article offers two compounded preparations supported by evidence-based data to treat oral mucositis. Expansion of the knowledge of the pathogenesis of mucositis as well as a better insight into individual risk factors will provide opportunities to improve management strategies.

Neonatal mucosal immunology.

PubMed

Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

2017-01-01

Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

Oral Mucosal Lesions in Indians From Northeast Brazil

PubMed Central

Cury, Patricia Ramos; Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; e Ribeiro, Livia Silva Figueiredo; de Aquino Xavier, Flavia Caló; Figueiredo, Andreia Leal; Ramalho, Luciana Maria Pedreira

2014-01-01

Abstract The aim of this cross-sectional study was to evaluate the prevalence of oral mucosal lesions, and their risk indicators in adult Kiriri Indians from Northeast Brazil. Clinical oral examination was performed on a representative sample of 223 Indians (age ≥19 years). A systematic evaluation of lips, labial mucosa and sulcus, commissures, buccal mucosa and sulcus, gingiva and alveolar ridge, tongue, floor of the mouth, and soft and hard palate was performed. Bivariate analysis was conducted to assess associations between mucosal conditions and age, gender, income, educational level, diabetic status, and smoking status. Mucosal lesions were found in 50 participants (22.4%). The most prevalent lesions were fistulae (6.2%) and traumatic ulcers (4.48%). Oral mucosal was associated with higher age (≥35 years; odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.05–3.76, P = 0.03) and lower education level (<9 years; OR = 2.13, 95% CI: 0.96–4.71, P = 0.06). Mucosal conditions are prevalent in Kiriri Indians and the presence of mucosal lesions is associated with advanced age and lower education. A public health program aimed at preventing and treating mucosal lesions and targeted toward the high-risk group is vital to improve the oral health status of this population. PMID:25501053

Anethole dithiolethione prevents oxidative damage in glutathione-depleted astrocytes.

PubMed

Drukarch, B; Schepens, E; Stoof, J C; Langeveld, C H

1997-06-25

Astrocytes protect neurons against reactive oxygen species such as hydrogen peroxide, a capacity which reportedly is abolished following loss of the antioxidant glutathione. Anethole dithiolethione, a sulfur-containing compound which is used in humans, is known to increase cellular glutathione levels and thought thereby to protect against oxidative damage. In the present study we found that anethole dithiolethione increased the glutathione content of cultured rat striatal astrocytes. This effect was abolished by coincubation with the glutathione synthesis inhibitor buthionine sulfoximine. Nevertheless, in the presence of buthionine sulfoximine, despite the lack of an increase in the lowered glutathione level, anethole dithiolethione fully protected the astrocytes against the enhanced toxicity of hydrogen peroxide. Thus, apparently other mechanisms than stimulation of glutathione synthesis are involved in the compound's protective action in astrocytes. Considering the occurrence of lowered glutathione levels in neurodegenerative syndromes, we conclude that further evaluation of the therapeutic potential of anethole dithiolethione is warranted.

Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity.

PubMed

Okada, Kazushi; Fukui, Masayuki; Zhu, Bao-Ting

2016-08-26

Glutathione depletion is a distinct cause underlying many forms of pathogenesis associated with oxidative stress and cytotoxicity. Earlier studies showed that glutamate-induced glutathione depletion in immortalized murine HT22 hippocampal neuronal cells leads to accumulation of reactive oxygen species (ROS) and ultimately cell death, but the precise mechanism underlying these processes is not clear. Here we show that during the induction of glutathione depletion, nitric oxide (NO) accumulation precedes ROS accumulation. While neuronal NO synthase (nNOS) in untreated HT22 cells exists mostly as a monomer, glutathione depletion results in increased formation of the dimer nNOS, accompanied by increases in the catalytic activity. We identified that nNOS dimerization is catalyzed by protein disulfide isomerase (PDI). Inhibition of PDI's isomerase activity effectively abrogates glutathione depletion-induced conversion of monomer nNOS into dimer nNOS, accumulation of NO and ROS, and cytotoxicity. Furthermore, we found that PDI is present in untreated cells in an inactive S-nitrosylated form, which becomes activated following glutathione depletion via S-denitrosylation. These results reveal a novel role for PDI in mediating glutathione depletion-induced oxidative cytotoxicity, as well as its role as a valuable therapeutic target for protection against oxidative cytotoxicity. Copyright © 2016. Published by Elsevier Inc.

Gastroprotection studies of Schiff base zinc (II) derivative complex against acute superficial hemorrhagic mucosal lesions in rats.

PubMed

Golbabapour, Shahram; Gwaram, Nura Suleiman; Hassandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Hadi, A Hamid A; Majid, Nazia Abdul

2013-01-01

The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats. The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10(-5) M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10(-5) and 4.362×10(-5) M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10(-5) M/kg). The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

Gastroprotection Studies of Schiff Base Zinc (II) Derivative Complex against Acute Superficial Hemorrhagic Mucosal Lesions in Rats

PubMed Central

Golbabapour, Shahram; Gwaram, Nura Suleiman; Hassandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Hadi, A. Hamid A; Majid, Nazia Abdul

2013-01-01

Background The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats. Methodology/Principal Finding The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10−5 M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10−5 and 4.362×10−5 M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10−5 M/kg). Conclusion/Significance The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism. PMID:24058648

Stricture of the afferent isoperistaltic tubular segment: a late and rare cause of bilateral dilation of the upper urinary tract after ileal bladder substitution.

PubMed

Kiss, Bernhard; Schöndorf, Daniel; Studer, Urs E; Roth, Beat

2013-08-01

To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results. Copyright © 2013 Elsevier Inc. All rights reserved.

Retrograde Endourological Management of Upper Urinary Tract Abnormalities in Patients with Ileal Conduit Urinary Diversion: A Dual-Center Experience.

PubMed

Olson, Louise; Satherley, Hywel; Cleaveland, Paul; Zelhof, Bachar; Mokete, Max; Neilson, Donald; Srirangam, Shalom

2017-09-01

Patients with ileal conduit urinary diversions are at an increased risk of long-term upper urinary tract (UUT) complications, including anastomotic strictures, infections, and urolithiasis. The reconstructed urinary system poses challenges for endoscopic manipulation. We present and describe our dual-center experience in performing retrograde ureteroscopy to treat or diagnose UUT abnormalities in patients with ileal conduit incontinent diversion. We performed a retrospective analysis of medical records for all patients with previous urinary diversion who underwent retrograde ureteroscopic procedures via the ileal loop in our institutions over a 9 year period (between June 2007 and August 2016). Fifty-four procedures were performed in 36 patients. Mean age was 61 (28-90) years. Average time from diversion to ureteroscopic procedure was 13.0 (0.08-53) years. Stone disease was the most common indication for intervention in 35.2% (19/54) of cases, with a stone-free rate of 78.9% (15/19). Other indications included surveillance of transitional-cell carcinoma in 22.2% (12/54), diagnostic flexible ureteroscopy (fURS) in 20.4% (11/54), stricture management in 11.1% (6/54), removal of encrusted stent/nephrostomy in 7.4% (4/54), urine leak after diversion in 1.9% (1/54), and miscellaneous in 1.9% (1/54). Successful retrograde access was possible in 74% (40/54) of cases. A long and tortuous ileal segment, too difficult to negotiate, was the most common cause of failure to access the UUT. In 13 out of 54 (24.1%) cases, retrograde fURS was combined with simultaneous percutaneous antegrade access. Six patients (11.1%) developed postprocedural pyrexia requiring additional antibiotic therapy, and one (1.9%) patient required embolization of the renal artery for ongoing bleeding. Median length of stay was 1 day (0-55), with 13 (24%) being performed as day-case procedures. Retrograde ureteroscopy in patients with ileal conduits can be technically challenging due to distorted anatomy

Effects of viscosity and fermentability of dietary fibre on nutrient digestibility and digesta characteristics in ileal-cannulated grower pigs.

PubMed

Hooda, Seema; Metzler-Zebeli, Barbara U; Vasanthan, Thavaratnam; Zijlstra, Ruurd T

2011-09-01

Relative contributions of two functional properties, viscosity and fermentability of dietary fibre, on apparent ileal digestibility (AID), apparent total tract digestibility (ATTD), digesta passage rate, N retention and SCFA concentration have not been established. Thus, eight ileal-cannulated pigs randomised in a double 4 × 4 Latin square were fed four diets based on maize starch and casein supplemented with 5 % of actual fibre in a 2 × 2 factorial arrangement: low-fermentable, low-viscous cellulose (CEL); low-fermentable, high-viscous carboxymethylcellulose (CMC); high-fermentable, low-viscous oat β-glucan (LBG); high-fermentable, high-viscous oat β-glucan (HBG). Viscosity and fermentability interacted to affect (P < 0·001) digesta viscosity and AID and ATTD of nutrients. These properties tended to interact to affect (P < 0·10) digesta passage rate and butyrate. Pigs fed the CMC diet had the lowest (P < 0·05) digesta passage rate and the highest (P < 0·001) AID of energy, crude protein and DM, and ATTD of energy and DM. Post-ileal DM digestibility was highest (P < 0·001) for pigs fed the CEL and HBG diets. Post-ileal DM digestibility had a negative, curvilinear relationship with the AID of energy and crude protein (R2 0·85 and 0·72, respectively; P < 0·001). Digesta viscosity had a less strong relationship with the AID of energy and crude protein (R2 0·45 and 0·36, respectively; P < 0·001). In conclusion, high-viscous, low-fermentable dietary fibre increases the proportion of a diet that is digested in the small intestine by reducing digesta passage rate.

Quantitation of protein S-glutathionylation by liquid chromatograph-tandem mass spectrometry: Correction for contaminating glutathione and glutathione disulfide

USDA-ARS?s Scientific Manuscript database

Protein S-glutathionylation is a posttranslational modification that links oxidative stimuli to reversible changes in cellular function. Protein-glutathione mixed disulfides (PSSG) are commonly quantified by the reduction of the disulfide and detection of the resultant glutathione species. This met...

In Vitro Selective Growth-Inhibitory Effect of 8-Hydroxyquinoline on Clostridium perfringens versus Bifidobacteria in a Medium Containing Chicken Ileal Digesta.

PubMed

Skrivanova, Eva; Van Immerseel, Filip; Hovorkova, Petra; Kokoska, Ladislav

2016-01-01

Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16-32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32-2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry.

Anorectal mucosal melanoma

PubMed Central

Malaguarnera, Giulia; Madeddu, Roberto; Catania, Vito Emanuele; Bertino, Gaetano; Morelli, Luca; Perrotta, Rosario Emanuele; Drago, Filippo; Malaguarnera, Michele; Latteri, Saverio

2018-01-01

Anorectal melanoma is an uncommon and aggressive mucosal melanocytic malignancy. Due to its rarity, the pre-operative diagnosis remains difficult. The first symptoms are non-specific such as anal bleeding, anal mass or pain. Although anorectal melanoma carries a poor prognosis; optimal therapeutics strategies are unclear. Surgical resection remains the mainstay of treatment. The optimal surgical procedure for primary tumours is controversial and can vary from wide local excision or endoscopic mucosal resection (EMR) to an abdomino-perineal resection. A high degree of uncertainly exists regarding the benefit of radiation therapy or chemotherapy. The treatment of advanced melanoma is evolving rapidly with better understanding of the disease biology and immunology. Considerable effort has been devoted to the identification of molecular determinants of response to target therapies and immunotherapy. PMID:29492238

Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

PubMed Central

Horton, Rachel E.; Vidarsson, Gestur

2013-01-01

Over recent years it has become increasingly apparent that mucosal antibodies are not only restricted to the IgM and IgA isotypes, but that also other isotypes and particularly IgG can be found in significant quantities at some mucosal surfaces, such as in the genital tract. Their role is more complex than traditionally believed with, among other things, the discovery of novel function of mucosal immunoglobulin receptors. A thorough knowledge in the source and function and mucosal immunoglobulins is particularly important in development of vaccines providing mucosal immunity, and also in the current climate of microbicide development, to combat major world health issues such as HIV. We present here a comprehensive review of human antibody mediated mucosal immunity. PMID:23882268

HIV infection and specific mucosal immunity: workshop 4B.

PubMed

Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

2011-04-01

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

Immunology of Gut Mucosal Vaccines

PubMed Central

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

PubMed

Hamarneh, Sulaiman R; Mohamed, Mussa M Rafat; Economopoulos, Konstantinos P; Morrison, Sara A; Phupitakphol, Tanit; Tantillo, Tyler J; Gul, Sarah S; Gharedaghi, Mohammad Hadi; Tao, Qingsong; Kaliannan, Kanakaraju; Narisawa, Sonoko; Millán, José L; van der Wilden, Gwendolyn M; Fagenholz, Peter J; Malo, Madhu S; Hodin, Richard A

2014-10-01

To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

The mitochondrial dicarboxylate and 2-oxoglutarate carriers do not transport glutathione

PubMed Central

Booty, Lee M.; King, Martin S.; Thangaratnarajah, Chancievan; Majd, Homa; James, Andrew M.; Kunji, Edmund R.S.; Murphy, Michael P.

2015-01-01

Glutathione carries out vital protective roles within mitochondria, but is synthesised in the cytosol. Previous studies have suggested that the mitochondrial dicarboxylate and 2-oxoglutarate carriers were responsible for glutathione uptake. We set out to characterise the putative glutathione transport by using fused membrane vesicles of Lactococcus lactis overexpressing the dicarboxylate and 2-oxoglutarate carriers. Although transport of the canonical substrates could be measured readily, an excess of glutathione did not compete for substrate uptake nor could transport of glutathione be measured directly. Thus these mitochondrial carriers do not transport glutathione and the identity of the mitochondrial glutathione transporter remains unknown. PMID:25637873

Effect of feeding level on ileal and total tract digestibility of nutrients and energy from soybean meal-based diets for piglets.

PubMed

Goerke, M; Mosenthin, R; Jezierny, D; Sauer, N; Piepho, H-P; Messerschmidt, U; Eklund, M

2014-12-01

A total of 36 piglets with an initial body weight (BW) of 5.6 ± 0.7 kg, fitted with simple T-cannulas at the distal ileum, were used to evaluate the effect of three graded feeding levels (50, 75 or 100 g/kg BW(0.75) day) on apparent ileal digestibility (AID) and total tract digestibility (ATTD) of dry matter (DM), nitrogen (N) and energy, and on ATTD of organic matter (OM), ether extracts (EE), neutral detergent fibre (NDF), acid detergent fibre (ADF) and digestible (DE), metabolisable (ME) and net energy (NE) content in soybean meal (SBM)-casein-cornstarch-based diets. The AID of DM, N and energy and ATTD of NDF, ADF and EE in the diets were not affected (p > 0.05) by the feed intake (FI) level. There was a small decrease in ATTD of DM, N (CP), OM, ash and energy, and in DE, ME and NE content in the diets (p < 0.05) with increasing FI level. The net disappearance in the large intestine (in % of ileal recovery) decreased for DM, N and energy (p < 0.05) with increasing FI level. The design of the study allowed for estimating ileal endogenous loss of N and total tract endogenous loss of ash, N and EE, for estimating corresponding true ileal and total tract digestibility values, and for estimating urinary endogenous N loss. High variability in estimates of ileal endogenous N loss and total tract endogenous losses of N, EE and ash reflects great variation in individual endogenous losses between animals. Estimation of true total tract digestibility of N, EE and ash by regression analysis was affected by their decrease in ATTD with increasing FI level, as estimates for true digestibility were lower compared to their apparent values. The present results suggest that FI level can affect both apparent and true total tract nutrient digestibility in piglets. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

A regenerative approach towards mucosal fenestration closure

PubMed Central

Gandi, Padma; Anumala, Naveen; Reddy, Amarender; Viswa Chandra, Rampalli

2013-01-01

Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases. PMID:23749826

Furosemide suppresses ileal and colonic contractility via interactions with GABA-A receptor in mice.

PubMed

Kaewsaro, Kannaree; Nualplub, Suparp; Bumrungsri, Sara; Khuituan, Pissared

2017-11-01

The loop diuretic furosemide has an action to inhibit Na + -K + -2Cl - co-transporter at the thick ascending limb of Henle's loop resulting in diuresis. Furosemide also has the non-diuretic effects by binding to GABA-A receptor which may involve the gastrointestinal tract. The aim of this study was to investigate the effects of furosemide on smooth muscle contractions in mice ileum and proximal colon. Each intestinal segment suspended in an organ bath was connected to a force transducer. Signal output of mechanical activity was amplified and recorded for analysis using PowerLab System. After equilibration, the intestine was directly exposed to furosemide, GABA, GABA-A receptor agonist (muscimol), or muscarinic receptor antagonist (atropine). Furosemide (50, 100 and 500 μmol L -1 ) acutely reduced the amplitude of ileal and colonic contraction. In the ileum, 1 mmol L -1 GABA and 10-60 μmol L -1 muscimol significantly increased the amplitude, whereas in the colon, 50-100 mmol L -1 GABA and 60 μmol L -1 muscimol decreased the contractions. The contractions were also significantly suppressed by atropine. To investigate the mechanisms underlying the inhibiting effect of furosemide, furosemide was added to the organ bath prior to the addition of muscimol or atropine. A comparison of furosemide combined with muscimol or atropine group and furosemide group showed no significant difference of the ileal contraction, but the amplitude of colonic contraction significantly decreased when compared to adding furosemide alone. These results suggest that furosemide can reduce the ileal and proximal colonic contraction mediated by blocking and supporting of GABA-A receptor, respectively, resulting in decreased acetylcholine release. © 2017 John Wiley & Sons Australia, Ltd.

[Glutathione participation in regulating the secretory function of the stomach].

PubMed

Shlygin, G K; Vasilevskaia, L S; Martinchik, A N; Ignatenko, L G

1987-01-01

In experiments on dogs with Pavlov's pouches it was shown that glutathione infusion into the blood produced a highly pronounced stimulating effect on the gastric secretion induced by pentagastrin. Endogenous glutathione produced similar effect. It was found that intake as a drink of mono-sodium glutamate led to a significant increase of glutathione concentration in the dogs' blood, that was, probably, the result of its intensified production in the intestinal wall and passing into the blood. The growth of glutathione concentration in the blood coincided with its stimulating effect on the gastric secretion. Glutathione administered separately into the blood, or intake of glutathione without pentagastrin did not produce stimulating effect on gastric secretion. The data presented have evidenced that glutathione, besides its known functions, plays a role of the factor engaged in the regulation of gastric secretion.

Clinical experience with the N-shaped ileal neobladder: assessment of complications, voiding patterns, and quality of life in our series of 58 patients.

PubMed

Joniau, S; Benijts, J; Van Kampen, M; De Waele, M; Ooms, J; Van Cleynenbreugel, B; Van Poppel, H

2005-05-01

The purpose of this retrospective study was to assess complications, voiding patterns, and quality of life in patients with an orthotopic bladder substitution, using an N-shaped ileal neobladder. Between May 1996 and December 2002, 58 patients (52 men and 6 women) underwent an orthotopic ileal neobladder reconstruction after radical cystectomy. The mean age was 47 for the female and 60 for the male patients. In all patients an N-shaped ileal pouch was constructed. This pouch has not yet been described in the literature before. All procedures were performed by the same surgeon (HVP) and the mean follow-up was 38 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), and as pouch-related and non-pouch-related. The patients took part in a pelvic floor re-education programme for as long as they were incontinent. All patients completed a retrospective Quality of Life questionnaire, based on the QLQ-C30 questionnaire, which was validated by the EORTC's Study Group on Quality of Life. In 38% of the patients, early complications occurred, whereas 48% had late complications. The most frequent early complications were diarrhea (24%) and pyelonephritis (9%). Diarrhea was again the most frequently mentioned non-pouch-related complication (19%). The most frequently observed pouch-related late complication was ileo-urethral stenosis. This occurred in five patients. All of these 5 patients were re-operated using a minimally invasive approach. Daytime continence was achieved in 95% of patients and nighttime continence in 66%. Hyper-continence with subsequent need for CISC was observed in 5 out of 6 women (83%) and 0 out of 52 men (0%). The retrospective QoL questionnaire learned that the impact of bladder removal and orthotopic bladder substitution has acceptable impact on patient's everyday life. Diarrhea was mentioned as being the most discomforting complication by most of the patients. We describe a modified orthotopic

Effects of dietary inclusion of silymarin on performance, intestinal morphology and ileal bacterial count in aflatoxin-challenged broiler chicks.

PubMed

Jahanian, E; Mahdavi, A H; Asgary, S; Jahanian, R

2017-10-01

This study was conducted to investigate the effect of dietary supplementation of silymarin on performance, jejunal morphology and ileal bacterial population in broiler chicks intoxicated with a mix of aflatoxins. A total of three hundred thirty six 7-day-old Ross broiler chicks were randomly distributed between seven experimental groups with four replicates of 12 birds each. Experimental treatments consisted of a control group (unchallenged), and a 2 × 3 factorial arrangement, including two aflatoxin levels (0.5 and 2 ppm) and three levels of silymarin (0, 500 and 1000 ppm). Birds were challenged with a mix of aflatoxins from 7 to 28 days of age. Results showed that increasing aflatoxin level resulted in decreased average daily feed intake (ADFI) and weight gain (ADWG), consequently impaired feed conversion ratio (FCR) throughout the trial period. Dietary supplementation of silymarin resulted in the marked increases in ADFI and ADWG, and improved FCR values in aflatoxin-challenged chicks. Ileal bacterial populations at days 28 and 42 of age were increased by incremental levels of aflatoxins. On the other hand, dietary silymarin supplementation suppressed ileal populations of Escherichia coli, Salmonella, Klebsiella and total negative bacteria in aflatoxicated birds. Increase in dietary aflatoxin level resulted in the decreased villi height, villi height-to-crypt depth ratio (VH:CD), villi surface area and apparent villi absorptive area, while it increased crypt depth, goblet cell count and lymphoid follicular diameter. Feeding silymarin at the level of 1000 ppm increased villi height and VH:CD in aflatoxicated birds. Present results indicate that dietary inclusion of silymarin could improve performance by suppressing ileal bacteria and enhancing absorptive surface area in aflatoxin-challenged broiler chicks. Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

PubMed

Deponte, Marcel

2017-11-20

Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron-sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron-sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal

Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

PubMed Central

Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

2013-01-01

Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

Modes of Action for Mucosal Vaccine Adjuvants.

PubMed

Aoshi, Taiki

Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action.

Microneedle and mucosal delivery of influenza vaccines

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

2017-01-01

In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

Effect of nabumetone and aspirin on colonic mucosal bleeding time.

PubMed

Basson, M D; Panzini, L; Palmer, R H

2001-04-01

The management of patients taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because of concerns over bleeding after biopsy or polypectomy. To determine whether patients using the NSAID nabumetone, a non-acidic prodrug with mixed activity against cyclooxygenase-1 (COX-1) and COX-2, exhibited prolonged mucosal bleeding times and how this might compare with mucosal bleeding times in patients using aspirin. We assessed triplicate mucosal bleeding times in patients undergoing screening flexible sigmoidoscopy. We compared 90 patients who had taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the investigator performing the study was blinded to the patient's medication. Mucosal bleeding times did not differ significantly among control or nabumetone-using patients. However, the patients receiving aspirin exhibited significant prolongation. Mucosal bleeding time correlated statistically significantly, but weakly, with skin bleeding time. Nabumetone does not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin bleeding time does not reliably screen for prolonged mucosal bleeding time.

Adenocarcinoma in the anal transitional zone after ileal pouch for ulcerative colitis: report of a case.

PubMed

Bell, Stephen W; Parry, B; Neill, M

2003-08-01

This article reports the seventh known case of adenocarcinoma arising in or adjacent to an ileal pouch after proctocolectomy for ulcerative colitis. It is the second reported case of adenocarcinoma in the anal transitional zone in this setting. A literature review is presented of the six previous cases published, and on the wider subject of how to best manage the anal transitional zone. It is concluded that this is a rare, but catastrophic, event with a potentially poor prognosis and can occur late (more than a decade) after the original surgery. All ileal pouches performed for ulcerative colitis should be followed for extended periods. The development of dysplasia necessitates close follow-up, including regular biopsies, and local excision and pouch advancement can manage persistent dysplasia. When operating for dysplasia or cancer, biopsies of the anal transitional zone should be performed or consideration given to mandatory mucosectomy.

A case of staghorn stones in a kidney with an ileal ureter treated by percutaneous nephrolithotomy.

PubMed

Gao, Xiaofeng; Zhou, Tie; Li, Jinyi; Sun, Yinghao

2008-12-01

A 59-year-old man was admitted to hospital for investigation of a 1-year history of intermittent hematuria. He had undergone ileal ureteral replacement for left renal stones 36 years earlier. Renal ultrasonography, physical examination, abdominal plain radiography, intravenous urography, CT urography, measurement of serum levels of creatinine, urea and electrolytes, renal scintigraphy, urinalysis and urine culture. Staghorn calculi in the left kidney, with a high-lying anastomosis between the renal pelvis and the proximal ileal segment. The patient underwent percutaneous nephrolithotomy via a middle-calyx access for the large staghorn stones. After surgery, no residual calculi were found and the patient was discharged with an uneventful postoperative course. At 1 month, renal scintigraphy showed normal bilateral kidney function. The patient received potassium citrate supplementation and was followed up with 6-monthly imaging studies. At the last report, he had been stone-free for 7 months.

The mitochondrial dicarboxylate and 2-oxoglutarate carriers do not transport glutathione.

PubMed

Booty, Lee M; King, Martin S; Thangaratnarajah, Chancievan; Majd, Homa; James, Andrew M; Kunji, Edmund R S; Murphy, Michael P

2015-02-27

Glutathione carries out vital protective roles within mitochondria, but is synthesised in the cytosol. Previous studies have suggested that the mitochondrial dicarboxylate and 2-oxoglutarate carriers were responsible for glutathione uptake. We set out to characterise the putative glutathione transport by using fused membrane vesicles of Lactococcus lactis overexpressing the dicarboxylate and 2-oxoglutarate carriers. Although transport of the canonical substrates could be measured readily, an excess of glutathione did not compete for substrate uptake nor could transport of glutathione be measured directly. Thus these mitochondrial carriers do not transport glutathione and the identity of the mitochondrial glutathione transporter remains unknown. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of polysaccharide peptides from COV-1 strain of Coriolus versicolor on glutathione and glutathione-related enzymes in the mouse.

PubMed

Yeung, John H K; Or, Penelope M Y

2007-06-01

The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.

The antioxidant master glutathione and periodontal health

PubMed Central

Bains, Vivek Kumar; Bains, Rhythm

2015-01-01

Glutathione, considered to be the master antioxidant (AO), is the most-important redox regulator that controls inflammatory processes, and thus damage to the periodontium. Periodontitis patients have reduced total AO capacity in whole saliva, and lower concentrations of reduced glutathione (GSH) in serum and gingival crevicular fluid, and periodontal therapy restores the redox balance. Therapeutic considerations for the adjunctive use of glutathione in management of periodontitis, in limiting the tissue damage associated with oxidative stress, and enhancing wound healing cannot be underestimated, but need to be evaluated further through multi-centered randomized controlled trials. PMID:26604952

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

PubMed Central

2017-01-01

Abstract Significance: Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron–sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Critical Issues: Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron–sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. Future Directions: A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling

Conjugations with glutathione. The enzymic conjugation of some chlorocyclohexenes

PubMed Central

Sims, P.; Grover, P. L.

1965-01-01

1. α-3,4,5,6-Tetrachlorocyclohex-1-ene and γ-2,3,4,5,6-pentachlorocyclohex-1-ene are conjugated with glutathione in vitro by a rat-liver enzyme that is probably glutathione S-aryltransferase. 2. Chlorocyclohexane and the α-, β-, γ- and δ-isomers of hexachlorocyclohexane were not substrates for rat-liver glutathione S-aryltransferase. 3. Glutathione-S-aryltransferase activity was present in tissue preparations of houseflies of insecticide-resistant and -susceptible strains. More activity was found in a dieldrin-resistant strain of houseflies fed on dieldrin than in either a dieldrin-resistant strain not fed on dieldrin or a control strain of dieldrin-susceptible houseflies. 4. Housefly soluble supernatant preparations converted S-(2-chloro-4-nitrophenyl)glutathione into the corresponding cysteine and mercapturic acid derivatives. PMID:14333551

Standardized Ileal Amino Acid Digestibility of Corn, Corn Distillers' Dried Grains with Solubles, Wheat Middlings, and Bakery By-Products in Broilers and Laying Hens.

PubMed

Adedokun, S A; Jaynes, P; Payne, R L; Applegate, T J

2015-10-01

Standardized ileal amino acid digestibility (SIAAD) of 5 samples of corn distillers dried grain with solubles (DDGS), 5 samples of bakery by-products (BBP), 3 samples of corn, and 1 sample of wheat middlings (WM) were evaluated in broilers and laying hens. Diets containing each of the 14 feed ingredients were evaluated in 21 day-old broiler chickens. The DDGS and BBP containing diets were fed to 30-week-old laying hens, while corn and wheat middling were evaluated in 50-week-old laying hens. All the diets were semi-purified with each feed ingredient being the only source of amino acid (AA). To obtain SIAAD values, apparent ileal AA digestibility was corrected for basal ileal endogenous AA losses using values generated from broilers and laying hens fed a nitrogen-free diet. Ileal crude protein digestibility for the 5 DDGS samples was higher (P < 0.05) in broilers than in laying hens. Broilers had higher SIAAD for DDGS 2, 3, 4, and 5 while there was no difference for DDGS 1 except for 4 AA where broilers had higher (P < 0.05) SIAAD values. Standardized ileal AA digestibility values for broilers were higher (P < 0.05) for BBP 1 and 4. Ileal CP digestibility for corn 1 was higher (P < 0.05) for broilers compared to laying hens, and SIAAD values for the 16 AA (9 indispensable and 7 dispensable) evaluated in this study were higher (P < 0.05) in broilers. Broilers had higher (P < 0.05) SIAAD values for 4 (histidine, leucine, phenylalanine, and valine) and 6 (histidine, leucine, methionine, phenylalanine, threonine, and valine) indispensable and 3 (cysteine, glutamic acid, and proline) and 4 (cysteine, glutamic acid, proline, and serine) dispensable AA for corn 2 and corn 3, respectively. No difference in SIAAD between broilers and laying hens was observed for WM. Results from this study confirm that high variability in digestibility exists between different samples of DDGS. Differences in SIAAD between broilers and laying hens were observed in some samples of

Development of plant-based mucosal vaccines against widespread infectious diseases.

PubMed

Salyaev, Rurick K; Rigano, Maria Manuela; Rekoslavskaya, Natalya I

2010-08-01

Mucosal vaccination is a perspective for the control of infectious diseases, since it is capable of inducing humoral and cell-mediated responses. In addition, the delivery of vaccines to mucosal surfaces makes immunization practice safe and acceptable, and eliminates needle-associated risks. Transgenic plants can be used as bioreactors for the production of mucosally delivered protective antigens. This technology shows great promise to simplify and decrease the cost of vaccine delivery. Herein, we review the development of mucosally administered vaccines expressed in transgenic plants. In particular, we evaluate the advantages and disadvantages of using plants for the production of mucosal vaccines against widespread infectious diseases such as HIV, hepatitis B and TB.

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence.

PubMed

O'Regan, Kevin; Breen, Micheál; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J; Hodi, F Stephen; Van den Abbeele, Annick D

2013-12-30

Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin.

Novosphingobium aromaticivorans uses a Nu-class glutathione S-transferase as a glutathione lyase in breaking the β-aryl ether bond of lignin

PubMed Central

Kontur, Wayne S.; Bingman, Craig A.; Olmsted, Charles N.; Wassarman, Douglas R.; Ulbrich, Arne; Gall, Daniel L.; Smith, Robert W.; Yusko, Larissa M.; Fox, Brian G.; Noguera, Daniel R.; Coon, Joshua J.; Donohue, Timothy J.

2018-01-01

As a major component of plant cell walls, lignin is a potential renewable source of valuable chemicals. Several sphingomonad bacteria have been identified that can break the β-aryl ether bond connecting most phenylpropanoid units of the lignin heteropolymer. Here, we tested three sphingomonads predicted to be capable of breaking the β-aryl ether bond of the dimeric aromatic compound guaiacylglycerol-β-guaiacyl ether (GGE) and found that Novosphingobium aromaticivorans metabolizes GGE at one of the fastest rates thus far reported. After the ether bond of racemic GGE is broken by replacement with a thioether bond involving glutathione, the glutathione moiety must be removed from the resulting two stereoisomers of the phenylpropanoid conjugate β-glutathionyl-γ-hydroxypropiovanillone (GS-HPV). We found that the Nu-class glutathione S-transferase NaGSTNu is the only enzyme needed to remove glutathione from both (R)- and (S)-GS-HPV in N. aromaticivorans. We solved the crystal structure of NaGSTNu and used molecular modeling to propose a mechanism for the glutathione lyase (deglutathionylation) reaction in which an enzyme-stabilized glutathione thiolate attacks the thioether bond of GS-HPV, and the reaction proceeds through an enzyme-stabilized enolate intermediate. Three residues implicated in the proposed mechanism (Thr51, Tyr166, and Tyr224) were found to be critical for the lyase reaction. We also found that Nu-class GSTs from Sphingobium sp. SYK-6 (which can also break the β-aryl ether bond) and Escherichia coli (which cannot break the β-aryl ether bond) can also cleave (R)- and (S)-GS-HPV, suggesting that glutathione lyase activity may be common throughout this widespread but largely uncharacterized class of glutathione S-transferases. PMID:29449375

Effect of perioperative feeding with fibre & arginine on morphometrics of ileum after surgical stress.

PubMed

Boylu, Sukru; Ozbas, Serdar; Bozdag, Ali Dogan; Culhaci, Nil; Tuncyurek, Pars; Yardim, Serhat

2005-08-01

Major surgeries as well as other types of injury have been shown to affect the gut function. Enteral diets influence intestinal mucosal morphometry to different extents depending on their composition. Little is known about the effects of these defined-formula diets in patients with surgical stress but no malnutrition. This experimental study was undertaken to compare the effects of different enteral diets on the mucosal morphometrics of small bowel in surgically stressed rats without malnutrition Male Wistar-Albino rats (n=84) weighing between 160-220 g were randomised into three groups. Group A received standard rat chow. Group B received a complete balanced nutrition supplemented with fibre, and the rats in Group C were given an isocaloric specialized elemental nutrition enriched with specific combination of nutrients and arginine. The feeding was started two days before the operation and continued until re-operation. Laparotomy, ileal transection, and end-to-end anastomosis was performed as the surgical procedure. The rats were sacrificed on days 0, 2 and 7 post-operatively. One cm of ileal segment containing the anastomosis was examined histologically. Parameters for intestinal mucosal morphometry (number of villi, villous height, mucosal thickness) and number of mucous containing cells were determined. Number of mucous cells per villus was significantly (P<0.05) higher in group A compared to groups B and C on days 0 and 2 post-operation. On day 7 villous height and mucosal thickness were also significantly higher in group A compared to the other two groups. Laparotomy and a minor surgical intervention such as small bowel transection was not a major surgical stress for intestinal mucosal atrophy in rats without malnutrition. The effect of fibre and arginine enriched defined-formula diets did not seem to improve intestinal mucosal changes in such a surgical stress model compared with normal rat chow.

Oral mucositis in head and neck cancer: risk, biology, and management.

PubMed

Sonis, Stephen T

2013-01-01

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis.1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course.2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy.3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD).4.

21 CFR 864.7375 - Glutathione reductase assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

21 CFR 864.7375 - Glutathione reductase assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

21 CFR 864.7375 - Glutathione reductase assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

21 CFR 864.7375 - Glutathione reductase assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

21 CFR 864.7375 - Glutathione reductase assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Glutathione reductase assay. 864.7375 Section 864.7375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7375 Glutathione...

Effect of glutathione on phytochelatin synthesis in tomato cells. [Lycopersicon esculentum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendum, M.L.; Gupta, S.C.; Goldsbrough, P.B.

Growth of cell suspension cultures of tomato, Lycopersicon esculentum Mill. cv VFNT-Cherry, in the presence of cadmium is inhibited by buthionine sulfoximine, an inhibitor of glutathione synthesis. Cell growth and phytochelatin synthesis are restored to cells treated with buthionine sulfoximine by the addition of glutathione to the medium. Glutathione stimulates the accumulation of phytochelatins in cadmium treated cells, indicating that availability of glutathione can limit synthesis of these peptides. Exogenous glutathione causes a disproportionate increase in the level of smaller phytochelatins, notably ({gamma}-Glu-Cys){sub 2}-Gly. In the presence of buthionine sulfoximine and glutathione, phytochelatins that are produced upon exposure to cadmiummore » incorporate little ({sup 35}S)cysteine, indicating that these peptides are probably not synthesized by sequential addition of cysteine and glutamate to glutathione.« less

Glutathione transferases, regulators of cellular metabolism and physiology.

PubMed

Board, Philip G; Menon, Deepthi

2013-05-01

The cytosolic glutathione transferases (GSTs) comprise a super family of proteins that can be categorized into multiple classes with a mixture of highly specific and overlapping functions. The review covers the genetics, structure and function of the human cytosolic GSTs with particular attention to their emerging roles in cellular metabolism. All the catalytically active GSTs contribute to the glutathione conjugation or glutathione dependant-biotransformation of xenobiotics and many catalyze glutathione peroxidase or thiol transferase reactions. GSTs also catalyze glutathione dependent isomerization reactions required for the synthesis of several prostaglandins and steroid hormones and the catabolism of tyrosine. An increasing body of work has implicated several GSTs in the regulation of cell signaling pathways mediated by stress-activated kinases like Jun N-terminal kinase. In addition, some members of the cytosolic GST family have been shown to form ion channels in intracellular membranes and to modulate ryanodine receptor Ca(2+) channels in skeletal and cardiac muscle. In addition to their well established roles in the conjugation and biotransformation of xenobiotics, GSTs have emerged as significant regulators of pathways determining cell proliferation and survival and as regulators of ryanodine receptors that are essential for muscle function. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki

Chemical-induced glutathione depletion is thought to be caused by two types of toxicological mechanisms: PHO-type glutathione depletion [glutathione conjugated with chemicals such as phorone (PHO) or diethyl maleate (DEM)], and BSO-type glutathione depletion [i.e., glutathione synthesis inhibited by chemicals such as L-buthionine-sulfoximine (BSO)]. In order to identify mechanism-based biomarker gene sets for glutathione depletion in rat liver, male SD rats were treated with various chemicals including PHO (40, 120 and 400 mg/kg), DEM (80, 240 and 800 mg/kg), BSO (150, 450 and 1500 mg/kg), and bromobenzene (BBZ, 10, 100 and 300 mg/kg). Liver samples were taken 3, 6, 9 andmore » 24 h after administration and examined for hepatic glutathione content, physiological and pathological changes, and gene expression changes using Affymetrix GeneChip Arrays. To identify differentially expressed probe sets in response to glutathione depletion, we focused on the following two courses of events for the two types of mechanisms of glutathione depletion: a) gene expression changes occurring simultaneously in response to glutathione depletion, and b) gene expression changes after glutathione was depleted. The gene expression profiles of the identified probe sets for the two types of glutathione depletion differed markedly at times during and after glutathione depletion, whereas Srxn1 was markedly increased for both types as glutathione was depleted, suggesting that Srxn1 is a key molecule in oxidative stress related to glutathione. The extracted probe sets were refined and verified using various compounds including 13 additional positive or negative compounds, and they established two useful marker sets. One contained three probe sets (Akr7a3, Trib3 and Gstp1) that could detect conjugation-type glutathione depletors any time within 24 h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate

LED phototherapy to prevent mucositis: a case report.

PubMed

Lang-Bicudo, Leticia; Eduardo, Fernanda De Paula; Eduardo, Carlos De Paula; Zezell, Denise Maria

2008-12-01

The purpose of this case report was to evaluate the efficacy of phototherapy using light-emitting diodes (LEDs) to prevent oral mucositis in a Hodgkin's disease patient treated with the ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) chemotherapy regimen. Mucositis is a common dose-limiting complication of cancer treatment, and if severe it can lead to alterations in treatment planning or suspension of cancer therapy, with serious consequences for tumor response and survival. Therefore, low-power lasers and more recently LEDs, have been used for oral mucositis prevention and management, with good results. In this study, a 34-year-old man received intraoral irradiation with an infrared LED array (880 nm, 3.6 J/cm2, 74 mW) for five consecutive days, starting on chemotherapy day 1. In each chemotherapy cycle, he received the ABVD protocol on days 1 and 15, and received LED treatment for 5 d during each cycle. To analyze the results, the World Health Organization (WHO) scale was used to grade his mucositis, and a visual analogue scale (VAS) was used for pain evaluation, on days 1, 3, 7, 10, and 13 post-chemotherapy. The results showed that the patient did not develop oral mucositis during the five chemotherapy cycles, and he had no pain symptoms. LED therapy was a safe and effective method for preventing oral mucositis in this case report. However, further randomized studies with more patients are needed to prove the efficacy of this method.

Do glutathione levels decline in aging human brain?

PubMed

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of glutathione/glutathione S-transferase antioxidant system in butyrate-inhibited vascular smooth muscle cell proliferation.

PubMed

Ranganna, Kasturi; Mathew, Omana P; Yatsu, Frank M; Yousefipour, Zivar; Hayes, Barbara E; Milton, Shirlette G

2007-11-01

Vascular smooth muscle cell (VSMC) proliferation is an important etiological factor in vascular proliferative diseases such as primary atherosclerosis, hypertension, arterial and in-stent restenosis, and transplant vasculopathy. Our studies established that butyrate, a bacterial fermentation product of dietary fiber and a chromatin modulator, is a potent inhibitor of VSMC proliferation. The cardiovascular health benefits of a high-fiber diet, the principle source of butyrate in the body, have been known for a long time, however, very little is known about the antiatherogenic potential of butyrate. Because oxidative stress plays an important role in the pathogenesis of atherosclerosis, we examined involvement of the glutathione/glutathione S-transferase (GST) antioxidant system in butyrate's inhibition of VSMC proliferation. Treatment of proliferating VSMCs with butyrate leads to the induction of several GSTs. Interestingly, our study also demonstrated the nuclear localization of GST-P1 (GST-7-7), which is considered to be a cytosolic protein; this was demonstrated using immunostaining and was corroborated by western blotting. Also, the butyrate-induced antiproliferative action, and the induction of GST-P1 and its nuclear localization are downregulated when butyrate is withdrawn. Furthermore, assessment of intracellular glutathione levels reveals their augmentation by butyrate. Conversely, butyrate treatment reduces the levels of reactive oxygen species in VSMCs. Collectively, the butyrate-treatment-related increase in glutathione content, the reduction in reactive oxygen species, the upregulation of GST and the nuclear localization of GST-P1 in growth-arrested VSMCs imply that butyrate's antiproliferative action involves modulation of the cellular redox state. Thus, induction of the glutathione/GST antioxidant system appears to have other regulatory role(s) besides detoxification and regulation of the cellular redox state, for example, cell-cycle control and cell

Modes of Action for Mucosal Vaccine Adjuvants

PubMed Central

2017-01-01

Abstract Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action. PMID:28436755

Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2016-07-01

Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.

Analysis of TSC1 mutation spectrum in mucosal melanoma.

PubMed

Ma, Meng; Dai, Jie; Xu, Tianxiao; Yu, Sifan; Yu, Huan; Tang, Huan; Yan, Junya; Wu, Xiaowen; Yu, Jiayi; Chi, Zhihong; Si, Lu; Cui, Chuanliang; Sheng, Xinan; Kong, Yan; Guo, Jun

2018-02-01

Mucosal melanoma is a relatively rare subtype of melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator TSC1 and evaluated its correlation with the clinicopathological features of mucosal melanoma. We collected 91 mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1. The overall mutation frequency of TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007). Our findings suggest that TSC1 mutations are frequent in mucosal melanoma. TSC1 mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of mucosal melanoma. Our data implicate the potential significance of TSC1 mutations for effective and specific drug therapy for mucosal melanoma.

Effectiveness of honey on radiation-induced oral mucositis, time to mucositis, weight loss, and treatment interruptions among patients with head and neck malignancies: A meta-analysis and systematic review of literature.

PubMed

Co, Jayson L; Mejia, Michael Benedict A; Que, Jocelyn C; Dizon, Janine Margarita R

2016-07-01

Mucositis is a disabling effect of radiotherapy in head and neck cancers. There is no current standard on management of radiation-induced mucositis. Honey has been shown to reduce radiation-induced mucositis. A systematic review and meta-analysis were undertaken to assess the ability of honey in reducing the severity of oral mucositis, time to mucositis, weight loss, and treatment interruptions. Eight studies were included and showed that honey was significantly better in lowering the risk for treatment interruptions, weight loss, and delaying time to mucositis, but not severity of mucositis. There is current evidence that honey is beneficial for patients with head and neck cancers by decreasing treatment interruptions, weight loss, and delaying the onset of oral mucositis, but not in decreasing peak mucositis score. In light of the results, honey is a reasonable treatment for radiation-induced mucositis, but more randomized clinical trials (RCTs) should be done. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1119-1128, 2016. © 2016 Wiley Periodicals, Inc.

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence

PubMed Central

O’Regan, Kevin; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J.; Stephen Hodi, F.; Van den Abbeele, Annick D.

2013-01-01

Abstract Purpose: Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. Materials and methods: This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38–76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. Results: At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Conclusion: Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin. PMID:24434078

Induction of glutathione synthesis and glutathione reductase activity by abiotic stresses in maize and wheat.

PubMed

Kocsy, Gábor; Szalai, Gabriella; Galiba, Gábor

2002-06-21

The effect of different abiotic stresses (extreme temperatures and osmotic stress) on the synthesis of glutathione and hydroxymethylglutathione, on the ratio of the reduced to oxidised forms of these thiols (GSH/GSSG, hmGSH/hmGSSG), and on the glutathione reductase (GR) activity was studied in maize and wheat genotypes having different sensitivity to low temperature stress. Cold treatment induced a greater increase in total glutathione (TG) content and in GR activity in tolerant genotypes of both species than in sensitive ones. The GSH/GSSG and hmGSH/hmGSSG ratios were increased by this treatment only in the frost-tolerant wheat variety. High-temperature stress increased the TG content and the GSH/GSSG ratio only in the chilling-sensitive maize genotype, but GR activity was greater after this treatment in both maize genotypes. Osmotic stress resulted in a great increase in the TG content in wheat and the GR activity in maize. The amount of total hydroxymethylglutathione increased following all stress treatments. These results indicate the involvement of these antioxidants in the stress responses of wheat and maize.

Interaction of glutathione with bovine serum albumin: Spectroscopy and molecular docking.

PubMed

Jahanban-Esfahlan, Ali; Panahi-Azar, Vahid

2016-07-01

This study aims to investigate the interaction between glutathione and bovine serum albumin (BSA) using ultraviolet-visible (UV-vis) absorption, fluorescence spectroscopies under simulated physiological conditions (pH 7.4) and molecular docking methods. The results of fluorescence spectroscopy indicated that the fluorescence intensity of BSA was decreased considerably upon the addition of glutathione through a static quenching mechanism. The fluorescence quenching obtained was related to the formation of BSA-glutathione complex. The values of KSV, Ka and Kb for the glutathione and BSA interaction were in the order of 10(5). The thermodynamic parameters including enthalpy change (ΔH), entropy change (ΔS) and also Gibb's free energy (ΔG) were determined using Van't Hoff equation. These values showed that hydrogen bonding and van der Waals forces were the main interactions in the binding of glutathione to BSA and the stabilization of the complex. Also, the interaction of glutathione and BSA was spontaneous. The effects of glutathione on the BSA conformation were determined using UV-vis spectroscopy. Moreover, glutathione was docked in BSA using ArgusLab as a molecular docking program. It was recognized that glutathione binds within the sub-domain IIA pocket in domain II of BSA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Examining the effect of dietary electrolyte balance, energy source, and length of feeding of nitrogen-free diets on ileal endogenous amino acid losses in broilers.

PubMed

Adedokun, S A; Pescatore, A J; Ford, M J; Jacob, J P; Helmbrecht, A

2017-09-01

The effect of dietary electrolyte balance (DEB), energy source (ES), and length of feeding of nitrogen-free diet (NFD) on ileal endogenous amino acid (EAA) loss in mg/kg dry matter intake (DMI) was evaluated in broiler chickens. In Experiment 1, 720 chickens consisting of 15 replicate cages with 6 chickens/replicate were used. Treatments were arranged in a 2 × 2 × 2 factorial and consisted of 4 NFD with 2 levels (low or high) of DEB and 2 ES [corn starch (CS) or dextrose (DX)], and 2 sampling time-points (diets were fed for either 72 h (d 16 to 19) or 120 h (d 16 to 21). Experiment 2 used 360 chickens in a 2 × 2 factorial arrangement of treatments with 2 levels (low or high) of DEB and 2 ES (CS or DX). Diets were fed for 72 h (d 18 to 21). All birds had access to feed and water on an ad libitum basis. Data were analyzed using the GLM procedure of SAS appropriate for a completely randomized design for a factorial arrangement of treatments. For Experiment 1, there were interactions (P < 0.05) between the 3 main factors for nitrogen and all the AA except Trp. Broilers that were fed DX-based NFD with high DEB for 72 h had the highest (P < 0.05) EAA losses. In Experiment 2, there was no interaction between DEB and ES except for His and Lys. When ileal EAA losses from birds fed the low DEB, CS-based NFD were used to standardize apparent ileal digestibility values from a previous study, there was no effect of length of feeding on standardized ileal AA digestibility values. In conclusion, DX-based NFD with high DEB increased endogenous AA loses. Despite differences in ileal EAA losses from CS-based NFD, standardized ileal AA digestibility values were not influenced by the length of feeding of NFD. Based on the results from these studies, NFD could be fed for 72 h without influencing SIAAD values. © 2017 Poultry Science Association Inc.

Ureteric catheterization via an ileal conduit: technique and retrieval of a JJ stent.

PubMed

Wah, T M; Kellett, M J

2004-11-01

Retrograde ureteric catheterization of a patient with an ileal conduit is difficult, because guide wires and catheters coil in the conduit. A modified loopogram, using a Foley catheter as a fulcrum through which catheters can be advanced to the ureteric anastomosis, is described. This technique was used to remove a JJ stent, which had been inserted previously across a stricture in one ureter, the stent crossing from one kidney to the other.

Impact of glutathione metabolism on zinc homeostasis in Saccharomyces cerevisiae.

PubMed

Steiger, Matthias G; Patzschke, Anett; Holz, Caterina; Lang, Christine; Causon, Tim; Hann, Stephan; Mattanovich, Diethard; Sauer, Michael

2017-06-01

Zinc is a crucial mineral for all organisms as it is an essential cofactor for the proper function of a plethora of proteins and depletion of zinc causes oxidative stress. Glutathione is the major redox buffering agent in the cell and therefore important for mitigation of the adverse effects of oxidative stress. In mammalian cells, zinc deficiency is accompanied by a glutathione depletion. In the yeast Saccharomyces cerevisiae, the opposite effect is observed: under low zinc conditions, an elevated glutathione concentration is found. The main regulator to overcome zinc deficiency is Zap1p. However, we show that Zap1p is not involved in this glutathione accumulation phenotype. Furthermore, we found that in glutathione-accumulating strains also the metal ion-binding phytochelatin-2, which is an oligomer of glutathione, is accumulated. This increased phytochelatin concentration correlates with a lower free zinc level in the vacuole. These results suggest that phytochelatin is important for zinc buffering in S. cerevisiae and thus explains how zinc homeostasis is connected with glutathione metabolism. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*

PubMed Central

Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

Effectiveness of a cranberry (Vaccinium macrocarpon) preparation in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty.

PubMed

Botto, Henry; Neuzillet, Yann

2010-04-01

Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty. Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry (Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control. Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1-93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13-60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment. Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies.

Health-related Quality of Life After Radical Cystectomy: A Cross-sectional Study With Matched-pair Analysis on Ileal Conduit vs Ileal Orthotopic Neobladder Diversion.

PubMed

Cerruto, Maria Angela; D'Elia, Carolina; Siracusano, Salvatore; Saleh, Omar; Gacci, Mauro; Cacciamani, Giovanni; De Marco, Vincenzo; Porcaro, Antonio Benito; Balzarro, Matteo; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Serni, Sergio; Carini, Marco; Verze, Paolo; Artibani, Walter

2017-10-01

To examine the different and health-related quality of life (HR-QoL) outcomes between ileal conduit (IC) and ileal orthotopic neobladder (IONB) in patients who underwent radical cystectomy (RC), by using validated self-reported cancer-specific instruments. This retrospective, cross-sectional, multicenter cohort study included 148 and 171 patients with either IC or IONB. HR-QoL was evaluated with Quality of Life Core Questionnaire and bladder module (BLM)-30 European Organisation for Research and Treatment of Cancer questionnaires. Baseline HR-QoL scores were dichotomized at the median to give "good" or "poor" score profiles. A matched-pair analysis compared HR-QoL aspects between 79 IC patients and 79 IONB patients. At univariate analysis IONB resulted favorable for physical functioning, emotional functioning, cognitive functioning (CF), fatigue, dyspnea, appetite loss, constipation (CO), and abdominal bloating flatulence (AB). At multivariate analyses, IONB showed better scores for emotional functioning (85 vs 79, P = .023), CF (93 vs 85, P <.001), CO (16 vs 31, P <.001), and AB (12 vs 25, P <.001). A significant worsening of sexual and urinary function was observed for IONB patients in the long-term. At matched-pair analysis, global health status was similar (65 vs 62, P = .385). Significantly better scores were observed in the IONB group for the following items: CF (P = .007), fatigue (P = .003), pain (P = .019), dyspnea (P = .016), CO (P = .001), and AB (P = .00). IONB and IC after RC were similar in terms of global health status. IONB provides better results in some aspects of HR-QoL related to bowel function, but a worsening of urinary and sexual functions. Further randomized controlled trials are needed to confirm these data. Copyright © 2017 Elsevier Inc. All rights reserved.

Mushrooms: A rich source of the antioxidants ergothioneine and glutathione.

PubMed

Kalaras, Michael D; Richie, John P; Calcagnotto, Ana; Beelman, Robert B

2017-10-15

While mushrooms are the highest dietary source for the unique sulfur-containing antioxidant ergothioneine, little is known regarding levels of the major biological antioxidant glutathione. Thus, our objectives were to determine and compare levels of glutathione, as well as ergothioneine, in different species of mushrooms. Glutathione levels varied >20-fold (0.11-2.41mg/gdw) with some varieties having higher levels than reported for other foods. Ergothioneine levels also varied widely (0.15-7.27mg/gdw) and were highly correlated with those of glutathione (r=0.62, P<0.001). Both antioxidants were more concentrated in pileus than stipe tissues in selected mushrooms species. Agaricus bisporus harvested during the third cropping flush contained higher levels of ergothioneine and glutathione compared to the first flush, possibly as a response to increased oxidative stress. This study demonstrated that certain mushroom species are high in glutathione and ergothioneine and should be considered an excellent dietary source of these important antioxidants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Velopharyngeal mucosal surface topography in healthy subjects and subjects with obstructive sleep apnea.

PubMed

Lambeth, Christopher; Amatoury, Jason; Wang, Ziyu; Foster, Sheryl; Amis, Terence; Kairaitis, Kristina

2017-03-01

Macroscopic pharyngeal anatomical abnormalities are thought to contribute to the pathogenesis of upper airway (UA) obstruction in obstructive sleep apnea (OSA). Microscopic changes in the UA mucosal lining of OSA subjects are reported; however, the impact of these changes on UA mucosal surface topography is unknown. This study aimed to 1 ) develop methodology to measure UA mucosal surface topography, and 2 ) compare findings from healthy and OSA subjects. Ten healthy and eleven OSA subjects were studied. Awake, gated (end expiration), head and neck position controlled magnetic resonance images (MRIs) of the velopharynx (VP) were obtained. VP mucosal surfaces were segmented from axial images, and three-dimensional VP mucosal surface models were constructed. Curvature analysis of the models was used to study the VP mucosal surface topography. Principal, mean, and Gaussian curvatures were used to define surface shape composition and surface roughness of the VP mucosal surface models. Significant differences were found in the surface shape composition, with more saddle/spherical and less flat/cylindrical shapes in OSA than healthy VP mucosal surface models ( P < 0.01). OSA VP mucosal surface models were also found to have more mucosal surface roughness ( P < 0.0001) than healthy VP mucosal surface models. Our novel methodology was utilized to model the VP mucosal surface of OSA and healthy subjects. OSA subjects were found to have different VP mucosal surface topography, composed of increased irregular shapes and increased roughness. We speculate increased irregularity in VP mucosal surface may increase pharyngeal collapsibility as a consequence of friction-related pressure loss. NEW & NOTEWORTHY A new methodology was used to model the upper airway mucosal surface topography from magnetic resonance images of patients with obstructive sleep apnea and healthy adults. Curvature analysis was used to analyze the topography of the models, and a new metric was derived to

Stabilization of anthocyanins in blackberry juice by glutathione fortification.

PubMed

Stebbins, Nathan B; Howard, Luke R; Prior, Ronald L; Brownmiller, Cindi; Mauromoustakos, Andy

2017-10-18

Blackberry anthocyanins provide attractive color and antioxidant activity. However, anthocyanins degrade during juice processing and storage, so maintaining high anthocyanin concentrations in berry juices may lead to greater antioxidant and health benefits for the consumer. This study evaluated potential additives to stabilize anthocyanins during blackberry juice storage. The anthocyanin stabilizing agents used were: glutathione, galacturonic acid, diethylenetriaminepentaacetic acid and tannic acid, which were added at a level of 500 mg L -1 . Juice anthocyanin, flavonol, and ellagitannin content and percent polymeric color were measured over five weeks of accelerated storage at 30 °C. Glutathione had the greatest protective effect on total anthocyanins and polymeric color. Therefore a second study was performed with glutathione in combination with lipoic and ascorbic acids in an effort to use antioxidant recycling to achieve a synergistic effect. However, the antioxidant recycling system had no protective effect relative to glutathione alone. Glutathione appears to be a promising blackberry juice additive to protect against anthocyanin degradation during storage.

Mucosal melanoma: an update.

PubMed

Ballester Sánchez, R; de Unamuno Bustos, B; Navarro Mira, M; Botella Estrada, R

2015-03-01

Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Enrichment of common carp (Cyprinus carpio) diet with medlar (Mespilus germanica) leaf extract: Effects on skin mucosal immunity and growth performance.

PubMed

Hoseinifar, Seyed Hossein; Khodadadian Zou, Hassan; Kolangi Miandare, Hamed; Van Doan, Hien; Romano, Nicholas; Dadar, Maryam

2017-08-01

A feeding trial was performed to assess the effects of dietary Medlar (Mespilus germanica) leaf extract (MLE) on the growth performance, skin mucus non-specific immune parameters as well as mRNA levels of immune and antioxidant related genes in the skin of common carp (Cyprinus carpio) fingerlings. Fish were fed diets supplemented with graded levels (0, 0.25, 0.50, and 1.00%) of MLE for 49 days. The results revealed an improvement to the growth performance and feed conversion ratio in MLE fed carps (P < 0.05), regardless of the inclusion level. The immunoglobulin levels and interleukin 8 levels in the skin mucous and skin, respectively, revealed significant increment in fish fed 1% MLE (P < 0.05) in comparison with the other MLE treatments and control group. Also, feeding on 0.25% and 0.50% MLE remarkably increased skin mucus lysozyme activity (P < 0.05). However, there were no significant difference between MLE treated groups and control (P > 0.05) in case protease activity in the skin mucous or tumor necrosis factor alpha and interleukin 1 beta gene expression in the skin of carps (P > 0.05). The expression of genes encoding glutathione reductase and glutathione S-transferase alpha were remarkably increased in MLE fed carps compared to the control group (P < 0.05) while carp fed 0.50% or 1.00% MLE had significantly increased glutathione peroxidase expression in their skin (P < 0.05). The present results revealed the potentially beneficial effects of MLE on the mucosal immune system and growth performance in common carp fingerlings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mucosal melanoma of the head and neck.

PubMed

Ascierto, Paolo Antonio; Accorona, Remo; Botti, Gerardo; Farina, Davide; Fossati, Piero; Gatta, Gemma; Gogas, Helen; Lombardi, Davide; Maroldi, Roberto; Nicolai, Piero; Ravanelli, Marco; Vanella, Vito

2017-04-01

Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery. Many new treatment options in the last years, in particular targeted therapies (i.e. inhibitors of c-KIT, NRAS/MEK or BRAF) and immunotherapies (anti CTLA-4 and anti PD-1/PD-L1 antibodies), have changed the history of cutaneous melanoma. Despite the different biology, mucosal melanoma is currently treated in the same way as cutaneous melanoma; however, patients with mucosal melanoma were excluded from the majority of recent clinical trials. Recent molecular findings offer new hope for the development of more effective systemic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

PubMed

Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

2017-06-01

The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, p<0.001, and p=0.031, respectively). Increased levels of AANAT, melatonin, and MT1 in the inflamed oral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

PubMed

Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

2013-01-01

Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

Endoscopic mucosal autograft for treating esophageal caustic strictures: preliminary human experience.

PubMed

He, Kexin; Zhao, Lili; Bu, Shoushan; Liu, Li; Wang, Xiang; Wang, Min; Fan, Zhining

2018-06-11

 Esophageal caustic stricture is a stubborn disease and postoperative restenosis limits the clinical efficacy of endoscopic dilation. Autologous mucosal grafts have been successfully applied in the treatment of urethral stricture and in the prevention of stricture after extensive mucosal resection. We aimed to use mucosal autografting performed endoscopically to treat refractory esophageal stricture. METHODS : Three patients with intractable corrosive esophageal stricture were treated endoscopically by combining dilation with autologous mucosal transplantation. RESULTS : All procedures were successful with no severe complications. Mucosal regeneration was shown at the transplanted segments. One patient was able to maintain a normal diet with complete remission after 1 year of follow-up. Intraluminal stenosis and dysphagia were significantly improved in another two patients. CONCLUSIONS : Mucosal autografting can achieve esophageal re-epithelialization, inhibit undesired fibrosis, prevent restenosis, and promote functional regeneration. © Georg Thieme Verlag KG Stuttgart · New York.

Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

PubMed

McNeela, E A; Lavelle, E C

2012-01-01

The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

Evaluation of dried vegetables residues for poultry: II. Effects of feeding cabbage leaf residues on broiler performance, ileal digestibility and total tract nutrient digestibility.

PubMed

Mustafa, A F; Baurhoo, B

2017-03-01

A study was conducted to investigate the effects of partial replacing corn and soybean meal with dried cabbage leaf residues (DCR) on broiler growth performance, apparent ileal nutrient digestibility, and apparent total tract nutrient utilization. Dietary treatments include 4 levels of DCR (0, 3, 6, and 9%). Two hundred and twenty-four day-old male broilers were randomly assigned to one of 4 groups (8 cage replicates; 7 birds/cage) and grown over a 35-d experimental period. Results showed that feeding DCR had no effects on daily body weigh gain (average 53.4 g/d), daily feed intake (average 94.9 g/d), and feed conversion ratio (average 1.78 g of feed/g of gain). Inclusion of DCR reduced apparent ileal DM (quadratic effect, P < 0.001), OM (linear effect, P = 0.012), and CP (quadratic effect, P = 0.001) digestibility of younger birds (d 21) while incremental levels of DCR had no effect on apparent ileal nutrient digestibilities of older birds (d 35). Apparent total tract digestibility of DM, OM, and CP increased (linear effect, P < 0.001) as the level of DCR increased. It was concluded that the inclusion of DCR in broiler diets up to 9% had no negative impact on bird performance and apparent ileal digestibility of older birds and improved apparent total tract nutrient digestibility. © 2016 Poultry Science Association Inc.

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice.

PubMed

Maioli, Tatiani Uceli; de Melo Silva, Brenda; Dias, Michelle Nobre; Paiva, Nivea Carolina; Cardoso, Valbert Nascimento; Fernandes, Simone Odilia; Carneiro, Cláudia Martins; Dos Santos Martins, Flaviano; de Vasconcelos Generoso, Simone

2014-04-11

The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii. S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil.

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments.

PubMed

Lai, Rocky; Afkhami, Sam; Haddadi, Siamak; Jeyanathan, Mangalakumari; Xing, Zhou

2015-06-01

Despite the use of bacille Calmette-Guérin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the lung interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the lung interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the lung interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines. Copyright ©ERS 2015.

Effect of limestone particle size and calcium to non-phytate phosphorus ratio on true ileal calcium digestibility of limestone for broiler chickens.

PubMed

Anwar, M N; Ravindran, V; Morel, P C H; Ravindran, G; Cowieson, A J

2016-10-01

The purpose of this study was to determine the effect of limestone particle size and calcium (Ca) to non-phytate phosphorus (P) ratio on the true ileal Ca digestibility of limestone for broiler chickens. A limestone sample was passed through a set of sieves and separated into fine (<0.5 mm) and coarse (1-2 mm) particles. The analysed Ca concentration of both particle sizes was similar (420 g/kg). Six experimental diets were developed using each particle size with Ca:non-phytate P ratios of 1.5:1, 2.0:1 and 2.5:1, with ratios being adjusted by manipulating the dietary Ca concentrations. A Ca-free diet was also developed to determine the basal ileal endogenous Ca losses. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to 6 replicate cages (8 birds per cage) and fed from d 21 to 24 post hatch. Apparent ileal digestibility of Ca was calculated using the indicator method and corrected for basal endogenous losses to determine the true Ca digestibility. The basal ileal endogenous Ca losses were determined to be 127 mg/kg of dry matter intake. Increasing Ca:non-phytate P ratios reduced the true Ca digestibility of limestone. The true Ca digestibility coefficients of limestone with Ca:non-phytate P ratios of 1.5, 2.0 and 2.5 were 0.65, 0.57 and 0.49, respectively. Particle size of limestone had a marked effect on the Ca digestibility, with the digestibility being higher in coarse particles (0.71 vs. 0.43).

Estimation of endogenous protein and amino acid ileal losses in weaned piglets by regression analysis using diets with graded levels of casein

PubMed Central

2013-01-01

Background Many studies have investigated endogenous loss of proteins and amino acids (AAs) at the ileal level in growing pigs. However, only a few studies have researched this subject in piglets. Knowledge regarding AA ileal digestibility in piglets would be helpful during the formulation of diets for weaning piglets, rather than just using coefficients obtained in growing pigs. Therefore, in this study, we sought to estimate endogenous protein and AA ileal losses in piglets. Furthermore, apparent and true ileal digestibility (AID and TID) of protein and AAs from casein were measured. Results The average flow of protein was 20.8 g/kg of dry matter intake (DMI). Basal protein loss, as estimated by regression, was 16.9 g/kg DMI. Glutamic acid, arginine, and aspartic acid (2.2, 1.4, and 1.2 g/kg DMI, respectively) were the AAs for which greater losses were seen. The AID of protein and AAs increased as the protein level in the diet increased. A higher increment in AID was observed between diets with 80 and160 g CP/kg of feed; this finding was mainly attributable to increases in glycine and arginine (46.1% and 18%, respectively). The TID of protein was 97.8, and the TID of AAs varied from 93.9 for histidine to 100.2 for phenylalanine. Conclusions The basal endogenous protein loss in piglets was 16.9 g/kg DMI. Endogenous protein was rich in glutamic acid, aspartic acid, and arginine, which represented 32.7% of endogenous protein loss in weaning piglets. The TID of casein was high and varied from 93.0 for histidine to 100.2 for phenylalanine. PMID:24053636

Glutathione maintenance is crucial for survival of melanocytes after exposure to rhododendrol.

PubMed

Kondo, Masatoshi; Kawabata, Keigo; Sato, Kohji; Yamaguchi, Sayuri; Hachiya, Akira; Takahashi, Yoshito; Inoue, Shintaro

2016-09-01

Rhododendrol is a phenolic compound that shows a tyrosinase-dependent toxicity for melanocytes and occasionally induces a vitiligo-like skin depigmentation. The post-tyrosinase mechanisms determining melanocyte death or survival, however, are far from clear. Here, we find that rhododendrol treatment leads to a reduction in the levels of cellular glutathione but also induces a cellular antioxidant response that eventually increases glutathione levels. We further find that rhododendrol toxicity is enhanced when glutathione levels are experimentally reduced and alleviated when glutathione levels are increased. Hence, it appears that the size of the preexisting glutathione pool along with the capacity to supply glutathione via the antioxidant response determines whether melanocytes survive or die after rhododendrol exposure. It is conceivable, therefore, that rhododendrol-induced leukoderma depends on the capacity to maintain appropriate glutathione levels and that enhancement of glutathione levels may preserve a patient's melanocytes and potentially help in repigmentation. © 2016 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder: technique and clinical outcomes.

PubMed

Shao, Pengfei; Li, Pu; Ju, Xiaobing; Qin, Chao; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Yin, Changjun

2015-02-01

To study the feasibility and safety of laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder and to evaluate the role of endoscopic stapling in neobladder construction. Fifty-five patients with bladder cancer who underwent laparoscopic radical cystectomy were retrospectively examined. Extended pelvic lymph node dissection was performed before cystectomy. An ileal segment of 50 cm was harvested to construct a U-shaped reservoir. The bottom of the reservoir was anastomosed with the posterior urethra. Twenty-five patients underwent neobladder construction by manual suturing and 30 patients by endoscopic stapler suturing. The mean operative time was 346 minutes, and mean neobladder construction time was 230 minutes. The median estimated blood loss was 500 mL, and 17 patients received intraoperative transfusion. Postoperative complications included 2 cases of urine leakage, 7 cases of pyelonephritis, 4 cases of incomplete bowel obstruction, 1 case of anastomotic stricture, and 1 case of death. Endoscopic stapler suturing for neobladder construction took significantly less time than manual suturing. However, neobladder stones were found in 2 patients who underwent operation using endoscopic suturing, and the stones were removed cystoscopically. The functional outcomes of the 2 constructive methods were comparable. Laparoscopic radical cystectomy with intracorporeal orthotopic neobladder is safe and feasible for experienced laparoscopic surgeons. Application of endoscopic stapler simplifies the surgical procedure while increasing the risk of neobladder stone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of mucosal adjuvants and immunization routes for the induction of systemic and mucosal humoral immune responses in macaques.

PubMed

Veazey, Ronald S; Siddiqui, Asna; Klein, Katja; Buffa, Viviana; Fischetti, Lucia; Doyle-Meyers, Lara; King, Deborah F; Tregoning, John S; Shattock, Robin J

2015-01-01

Delivering vaccine antigens to mucosal surfaces is potentially very attractive, especially as protection from mucosal infections may be mediated by local immune responses. However, to date mucosal immunization has had limited successes, with issues of both safety and poor immunogenicity. One approach to improve immunogenicity is to develop adjuvants that are effective and safe at mucosal surfaces. Differences in immune responses between mice and men have overstated the value of some experimental adjuvants which have subsequently performed poorly in the clinic. Due to their closer similarity, non-human primates can provide a more accurate picture of adjuvant performance. In this study we immunised rhesus macaques (Macaca mulatta) using a unique matrix experimental design that maximised the number of adjuvants screened while reducing the animal usage. Macaques were immunised by the intranasal, sublingual and intrarectal routes with the model protein antigens keyhole limpet haemocyanin (KLH), β-galactosidase (β-Gal) and ovalbumin (OVA) in combination with the experimental adjuvants Poly(I:C), Pam3CSK4, chitosan, Thymic Stromal Lymphopoietin (TSLP), MPLA and R848 (Resiquimod). Of the routes used, only intranasal immunization with KLH and R848 induced a detectable antibody response. When compared to intramuscular immunization, intranasal administration gave slightly lower levels of antigen specific antibody in the plasma, but enhanced local responses. Following intranasal delivery of R848, we observed a mildly inflammatory response, but no difference to the control. From this we conclude that R848 is able to boost antibody responses to mucosally delivered antigen, without causing excess local inflammation.

Directed evolution of glutathione transferases towards a selective glutathione-binding site and improved oxidative stability.

PubMed

Axarli, Irine; Muleta, Abdi W; Chronopoulou, Evangelia G; Papageorgiou, Anastassios C; Labrou, Nikolaos E

2017-01-01

Glutathione transferases (GSTs) are a family of detoxification enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic compounds. A library of alpha class GSTs was constructed by DNA shuffling using the DNA encoding the human glutathione transferase A1-1 (hGSTA1-1) and the rat glutathione transferase A1-1 (rGSTA1-1). Activity screening of the library allowed the selection of a chimeric enzyme variant (GSTD4) that displayed high affinity towards GSH and GSH-Sepharose affinity adsorbent, higher k cat /K m and improved thermal stability, compared to the parent enzymes. The crystal structures of the GSTD4 enzyme in free form and in complex with GSH were determined to 1.6Šand 2.3Šresolution, respectively. Analysis of the GSTD4 structure showed subtle conformational changes in the GSH-binding site and in electron-sharing network that may contribute to the increased GSH affinity. The shuffled variant GSTD4 was further optimized for improved oxidative stability employing site-saturation mutagenesis. The Cys112Ser mutation confers optimal oxidative stability and kinetic properties in the GSTD4 enzyme. DNA shuffling allowed the creation of a chimeric enzyme variant with improved properties, compared to the parent enzymes. X-ray crystallography shed light on how recombination of a specific segment from homologous GSTA1-1 together with point mutations gives rise to a new functionally competent enzyme with improved binding, catalytic properties and stability. Such an engineered GST would be useful in biotechnology as affinity tool in affinity chromatography as well as a biocatalytic matrix for the construction of biochips or enzyme biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

The oesophageal zero-stress state and mucosal folding from a GIOME perspective

PubMed Central

Liao, Donghua; Zhao, Jingbo; Yang, Jian; Gregersen, Hans

2007-01-01

The oesophagus is a cylindrical organ with a collapsed lumen and mucosal folds. The mucosal folding may serve to advance the function of the oesophagus, i.e. the folds have a major influence on the flow of air and bolus through the oesophagus. Experimental studies have demonstrated oesophageal mucosal folds in the no-load state. This indicates that mucosal buckling must be considered in the analysis of the mechanical reference state since the material stiffness drops dramatically after tissue collapse. Most previous work on the oesophageal zero-stress state and mucosal folding has been experimental. However, numerical analysis offers a promising alternative approach, with the additional ability to predict the mucosal buckling behaviour and to calculate the regional stress and strain in complex structures. A numerical model used for describing the mechanical behaviour of the mucosal-folded, three-layered, two-dimensional oesophageal model is reviewed. GIOME models can be used in the future to predict the tissue function physiologically and pathologically. PMID:17457964

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat.

PubMed

Sukhotnik, Igor; Helou, Habib; Mogilner, Jorge; Lurie, Michael; Bernsteyn, Aleksander; Coran, Arnold G; Shiloni, Eitan

2005-03-01

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia-reperfusion (IR) in the rat. Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.

The effect of microbial phytase on ileal phosphorus and amino acid digestibility in the broiler chicken.

PubMed

Rutherfurd, S M; Chung, T K; Moughan, P J

2002-09-01

1. The study aimed to assess the effect of a commercially available microbial phytase on phytate phosphorus and total phosphorus content at the terminal ileum as well as true ileal amino acid digestibility. 2. Five diets, each containing a different plant-based feedstuff, were supplemented with microbial phytase and fed, along with a non-supplemented corresponding diet, to 28-d-old broiler chickens, Chromic oxide was used as an indigestible marker. Ileal contents were collected and analysed, along with the diets, for total phosphorus, phytate phosphorus and amino acids. 3. Endogenous phosphorus determined at the terminal ileum was 272 +/- 108 mg/kg food dry matter (mean +/- SE). Endogenous ileal amino acid flows ranged from 58 +/- 10 mg/kg food dry matter for methionine to 568 +/- 47 mg/kg food dry matter for glutamic acid. 4. Supplementation with microbial phytase resulted in a significantly greater phytate P disappearance from the terminal ileum for rice bran (17% units), but not for soyabean meal, maize, wheat or rapeseed meal. Similarly total phosphorus digestibility was significantly (P < 0.05) higher when microbial phytase was added to the rice-bran-based diet but not for any of the other feedstuffs. 5. Amino acid digestibility was significantly greater in the presence of microbial phytase for all the amino acids examined in wheat, for several of the amino acids each in maize and rapeseed meal and for one amino acid in rice bran and soyabean meal. The average increase in amino acid digestibility for those amino acids affected, was 13, 6, 10, 7 and 12% units for wheat, maize, rapeseed meal, rice bran and soyabean meal, respectively. 6. It appears that microbial phytase improves phosphorus digestibility and amino acid digestibility for certain plant-based feedstuffs.

Effect of fish oil on glutathione redox system in multiple sclerosis

PubMed Central

Sorto-Gomez, Tania E; Ortiz, Genaro G; Pacheco-Moises, Fermín P; Torres-Sanchez, Erandis D; Ramirez-Ramirez, Viridiana; Macias-Islas, Miguel A; de la Rosa, Alfredo Celis; Velázquez-Brizuela, Irma E

2016-01-01

Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system. Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are implicated in the induction and progression of MS. Evidence suggests that Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory, antioxidant and neuroprotective effects. The aim of the present work was to evaluate the effect of fish oil on the activity of glutathione reductase (GR), content of reduced and oxidized glutathione, and GSH/GSSG ratio in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. Fish oil supplementation resulted in a significant increase in n-3 fatty acids and a decrease n-6 fatty acids. No differences in glutathione reductase activity, content of reduced and oxidized glutathione, and GSH/GSSG ratio were found. Conclusion: Glutathione reductase activity was not significantly different between the groups; however, fish oil supplementation resulted in smaller increase in GR compared with control group, suggesting a possible effect on antioxidant defence mechanisms. PMID:27335704

Glutathione and glutamate in schizophrenia: a 7T MRS study.

PubMed

Kumar, Jyothika; Liddle, Elizabeth B; Fernandes, Carolina C; Palaniyappan, Lena; Hall, Emma L; Robson, Siân E; Simmonite, Molly; Fiesal, Jan; Katshu, Mohammad Z; Qureshi, Ayaz; Skelton, Michael; Christodoulou, Nikolaos G; Brookes, Matthew J; Morris, Peter G; Liddle, Peter F

2018-06-22

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with "residual schizophrenia", in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment.

PubMed

Saadeh, Claire E

2005-04-01

Oral mucositis is a frequently encountered and potentially severe complication associated with administration of chemotherapy and radiotherapy. Although many pharmacologic interventions have been used for the prevention and treatment of oral mucositis, there is not one universally accepted strategy for its management. Most preventive and treatment strategies are based on limited, often anecdotal, clinical data. Basic oral hygiene and comprehensive patient education are important components of care for any patient with cancer at risk for development of oral mucositis. Nonpharmacologic approaches for the prevention of oral mucositis include oral cryotherapy for patients receiving chemotherapy with bolus 5-fluorouracil, and low-level laser therapy for patients undergoing hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic growth factors, pentoxifylline, glutamine, and several other agents have all been investigated for prevention of oral mucositis. Results have been conflicting, inconclusive, or of limited benefit. Treatment of established mucositis remains a challenge and focuses on a palliative management approach. Topical anesthetics, mixtures (also called cocktails), and mucosal coating agents have been used despite the lack of experimental evidence supporting their efficacy. Investigational agents are targeting the specific mechanisms of mucosal injury; among the most promising of these is recombinant human keratinocyte growth factor.

Glutathione protects Candida albicans against horseradish volatile oil.

PubMed

Bertóti, Regina; Vasas, Gábor; Gonda, Sándor; Nguyen, Nhat Minh; Szőke, Éva; Jakab, Ágnes; Pócsi, István; Emri, Tamás

2016-10-01

Horseradish essential oil (HREO; a natural mixture of different isothiocyanates) had strong fungicide effect against Candida albicans both in volatile and liquid phase. In liquid phase this antifungal effect was more significant than those of its main components allyl, and 2-phenylethyl isothiocyanate. HREO, at sublethal concentration, induced oxidative stress which was characterized with elevated superoxide content and up-regulated specific glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. Induction of specific glutathione S-transferase activities as marker of glutathione (GSH) dependent detoxification was also observed. At higher concentration, HREO depleted the GSH pool, increased heavily the superoxide production and killed the cells rapidly. HREO and the GSH pool depleting agent, 1-chlore-2,4-dinitrobenzene showed strong synergism when they were applied together to kill C. albicans cells. Based on all these, we assume that GSH metabolism protects fungi against isothiocyanates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sonographic diagnosis of fetal intestinal volvulus with ileal atresia: a case report.

PubMed

Yu, Wang; Ailu, Cai; Bing, Wang

2013-05-01

Fetal intestinal volvulus is a rare life-threatening condition usually manifesting after birth with most cases being associated with intestinal malrotation. It appears on prenatal sonography (US) as a twisting of the bowel loops around the mesenteric artery, leading to mechanical obstruction and ischemic necrosis of the bowel. We report a case of intrauterine intestinal volvulus with ileal atresia, suspected when US revealed a typical "whirlpool" sign at 37 weeks' gestation, with a segment of markedly distended bowel loops and small amount of fetal ascites. Copyright © 2012 Wiley Periodicals, Inc.

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice

PubMed Central

2014-01-01

Background The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. Results After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii. Conclusions S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil. PMID:24721659

Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis.

PubMed

Borok, Z; Buhl, R; Grimes, G J; Bokser, A D; Hubbard, R C; Holroyd, K J; Roum, J H; Czerski, D B; Cantin, A M; Crystal, R G

1991-07-27

Idiopathic pulmonary fibrosis (IPF) is characterised by alveolar inflammation, exaggerated release of oxidants, and subnormal concentrations of the antioxidant glutathione in respiratory epithelial lining fluid (ELF). Glutathione (600 mg twice daily for 3 days) was given by aerosol to 10 patients with IPF. Total ELF glutathione rose transiently, ELF oxidised glutathione concentrations increased, and there was a decrease in spontaneous superoxide anion release by alveolar macrophages. Thus, glutathione by aerosol could be a means of reversing the oxidant-antioxidant imbalance in IPF.

Prophylaxis for mucositis induced by ambulatory chemotherapy: systematic review.

PubMed

Manzi, Natália de Melo; Silveira, Renata Cristina de Campos Pereira; dos Reis, Paula Elaine Diniz

2016-04-01

The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy. Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence. Quantitative systematic review. Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy. Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose. Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each. There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions. © 2015 John Wiley & Sons Ltd.

Using Light to Treat Mucositis and Help Wounds Heal

NASA Technical Reports Server (NTRS)

Ignatius, Robert W.; Martin, Todd S.; Kirk, Charles

2008-01-01

A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

PubMed Central

Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

2015-01-01

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

Differential Apoptosis in Mucosal and Dermal Wound Healing

PubMed Central

Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

2014-01-01

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; p<0.05), Casp7 (at D5; p<0.05), Trp53 (at 24 h and D5; p<0.05), Tnfrsf1b (at 24 h; p<0.05), FasR (at 24 h, D5, and D7; p<0.05), and Casp8 (at 24 h; p<0.05) and significantly lower gene expression of Tradd (at 24 h; p<0.05). Innovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione*

PubMed Central

Kaur, Amandeep; Gautam, Ruchi; Srivastava, Ritika; Chandel, Avinash; Kumar, Akhilesh; Karthikeyan, Subramanian; Bachhawat, Anand Kumar

2017-01-01

Glutathione degradation plays an important role in glutathione and redox homeostasis, and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows ∼50% sequence identity. Human and mouse ChaC2 proteins purified in vitro show 10–20-fold lower catalytic efficiency than ChaC1, although they showed comparable Km values (Km of 3.7 ± 0.4 mm and kcat of 15.9 ± 1.0 min−1 toward glutathione for human ChaC2; Km of 2.2 ± 0.4 mm and kcat of 225.2 ± 15 min−1 toward glutathione for human ChaC1). The ChaC1 and ChaC2 proteins also shared the same specificity for reduced glutathione, with no activity against either γ-glutamyl amino acids or oxidized glutathione. The ChaC2 proteins were found to be expressed constitutively in cells, unlike the tightly regulated ChaC1. Moreover, lower eukaryotes have a single member of the ChaC family that appears to be orthologous to ChaC2. In addition, we determined the crystal structure of yeast ChaC2 homologue, GCG1, at 1.34 Å resolution, which represents the first structure of the ChaC family of proteins. The catalytic site is defined by a fortuitous benzoic acid molecule bound to the crystal structure. The mechanism for binding and catalytic activity of this new enzyme of glutathione degradation, which is involved in continuous but basal turnover of cytosolic glutathione, is proposed. PMID:27913623

Estimation of the standardized ileal digestible valine to lysine ratio in 13- to 32-kilogram pigs

USDA-ARS?s Scientific Manuscript database

Three experiments were conducted to determine the optimum standardized ileal digestible Val to Lys (SID Val:Lys) ratio for 13 to 32 kg pigs. In Exp. 1, a Val deficient basal diet containing 0.60% L-Lys•HCl, 1.21% SID Lys, and 0.68% SID Val was developed (0.56 SID Val:Lys). Performance of pigs fed th...

Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

PubMed Central

Strobel, S; Busuttil, A; Ferguson, A

1983-01-01

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6826106

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

PubMed

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Glutathione Metabolism and Parkinson’s Disease

PubMed Central

Smeyne, Michelle

2013-01-01

It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease. PMID:23665395

Prospective study of the impact on quality of life of cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction.

PubMed

Guillotreau, Julien; Castel-Lacanal, Evelyne; Roumiguié, Mathieu; Bordier, Benoit; Doumerc, Nicolas; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2011-11-01

Neurogenic bladder dysfunction has a negative impact on the patient's quality of life (QoL). Cystectomy with ileal conduit urinary diversion is a treatment option in patients in failure after conservative management. The objective of this study was to evaluate the impact of ileal conduit urinary diversion on the QoL of patients with neurogenic bladder dysfunction. From March 2004 to November 2010, 48 patients (36 women and 12 men with a mean age of 50.6  ±  11.8 years) treated by cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction, prospectively completed, before and after surgery, two self-administered QoL questionnaires. Neurological diseases were multiple sclerosis in 38 cases, spinal cord injury in 7 cases, and other neurological disease in 3 cases. Cystectomy was performed by laparoscopy in all patients. QoL was measured by using two self-administered questionnaires, one questionnaire specific for urinary disorders validated in neurological patients, Qualiveen®, and the generic SF36-v2® questionnaire. Data were compared by Student's t test. Comparison of the Qualiveen® self-administered questionnaire scores and indices before and after surgery showed that, after surgery, patients presented a significant reduction of limitations (0.57 ± 0.64 vs. 1.55 ± 1.35, P < 0.001), constraints (2.12  ±  0.83 vs. 2.64  ±  1.12, P = 0.046) scores and the SIUP index (1.29 ± 0.65 vs. 1.79 ± 0.95, P = 0.015). No significant change in SF36-v2® scores was observed postoperatively. Ileal conduit urinary diversion improves the urinary QoL of patients with neurogenic bladder dysfunction by decreasing limitations and constraints induced by urinary disorders, but has no impact on general QoL. Copyright © 2011 Wiley Periodicals, Inc.

The effects of glutathione depletion on thermotolerance and heat stress protein synthesis.

PubMed Central

Russo, A.; Mitchell, J. B.; McPherson, S.

1984-01-01

The effects of cellular glutathione depletion by buthionine sulfoximine on the development of thermotolerance and synthesis of heat stress protein was studied. Cellular glutathione levels were found to increase rapidly following an acute heat treatment of either 12 min at 45.5 degrees C or 1 h at 43 degrees C and remain elevated for prolonged periods. Glutathione depletion and prevention of glutathione synthesis by buthionine sulfoximine resulted in inhibition of the development of thermotolerance and a decrease in total protein as well as specific heat stress proteins. While the degree of inhibition of thermotolerance was similar for both glutathione depletion protocols, inhibition in heat stress protein synthesis was greater when glutathione was depleted to low levels prior to heating. The possible role of glutathione and the cellular redox state to thermotolerance and synthesis of heat stress protein is discussed. Images Figure 2 PMID:6733022

Mucosal vaccines to prevent porcine reproductive and respiratory syndrome: a new perspective.

PubMed

Renukaradhya, Gourapura J; Dwivedi, Varun; Manickam, Cordelia; Binjawadagi, Basavaraj; Benfield, David

2012-06-01

Porcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased incidence and recurrence of PRRS in swine herds. Current live and killed PRRSV vaccines administered by a parenteral route are ineffective in inducing complete protection. Thus, new approaches in design and delivery of PRRSV vaccines are needed to reduce the disease burden of the swine industry. Induction of an effective mucosal immunity to several respiratory pathogens by direct delivery of a vaccine to mucosal sites has proven to be effective in a mouse model. However, there are challenges in eliciting mucosal immunity to PRRS due to our limited understanding of safe and potent mucosal adjuvants, which could potentiate the mucosal immune response to PRRSV. The purpose of this review is to discuss methods for induction of protective mucosal immune responses in the respiratory tract of pigs. The manuscript also discusses how PRRSV modulates innate, adaptive and immunoregulatory responses at both mucosal and systemic sites of infected and/or vaccinated pigs. This information may help in the design of innovative mucosal vaccines to elicit superior cross-protective immunity against divergent field strains of PRRSV.

Natural Products for Management of Oral Mucositis Induced by Radiotherapy and Chemotherapy

PubMed Central

Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal

2015-01-01

Oral mucositis is a common side effect of systemic chemotherapy and radiotherapy of head and neck in patients with cancer. Severe oral mucositis is painful and affects oral functions, including intake of food and medications and speech. Prevention of oral mucositis affects the life quality of patients. Recent studies have been focused on natural products to improve or reduce this complication. Many clinical trials have been performed to assess natural products for treatment of mucositis and their results are promising. The authors reviewed the evidence for natural products in the prevention and treatment of oral mucositis induced by radiation therapy and chemotherapy. PMID:26306626

The effect of drying method temperature, collection method, and marker type on apparent ileal amino acid digestibility in 21-day-old broilers fed corn-soybean meal-barley based diet.

PubMed

Olojede, O C; Ford, M J; Jacob, J P; Ao, T; Pescatore, A J; Adedokun, S A

2018-06-01

For accurate estimation of nutrient digestibility, an ideal drying and sampling method is required to preserve the quality of the digesta. A standard corn-soybean meal (corn-SBM) broiler starter diet was fed from d 0 to 10 before birds were placed on the experimental diets until d 21. One hundred and sixty-eight male Cobb 500 broiler chicks were used to evaluate the effect of two drying methods (freeze-dryer vs. forced air-oven) and two drying temperatures (40 vs. 55°C) (Exp 1), while ninety-six chicks were used to evaluate the effect of flushing and squeezing as well as marker types (titanium vs. chromium) on apparent ileal DM, N, Ca, P, and AA digestibility (Exp 2). There were seven (Exp 1) or eight (Exp 2) replicate cages per treatment with 6 birds/cage. Digesta from the distal two thirds of the ileum was obtained from birds following euthanasia on d 21 by squeezing (Exp 1) and squeezing or flushing (Exp 2). Samples collected were stored in the freezer at -20°C until they were either freeze-dried (FD) or oven-dried (OD) at 40 or 55°C. There were no interactions between the drying methods and drying temperatures (Exp 1) on apparent ileal DM, N, and AA digestibility. Met had the highest (92.3%) while Cys had the lowest (73.8%) digestibility value. In Exp 2, no interaction between sampling methods and marker types was observed. The effect of sampling methods was not significant except for Arg and Met where squeezing resulted in higher (P < 0.05) digestibility values. Furthermore, apparent ileal His, Ile, Cys, Ser, and Tyr digestibility tended to be higher (P < 0.1) in squeezed digesta compared to the flushed digesta. Results from these studies showed that OD ileal digesta at 40 or 55°C had no negative effect on apparent ileal AA digestibility. Likewise, marker type did not influence apparent ileal AA digestibility values.

Intestinal colonization with Candida albicans and mucosal immunity

PubMed Central

Bai, Xiao-Dong; Liu, Xian-Hua; Tong, Qing-Ying

2004-01-01

AIM: To observe the relationship between intestinal lumen colonization with Candida albicans and mucosal secretory IgA (sIgA). METHODS: A total of 82 specific-pathogen-free mice were divided randomly into control and colonization groups. After Candida albicans were inoculated into specific-pathogen-free mice, the number of Candida albicans adhering to cecum and mucosal membrane was counted. The lymphocyte proliferation in Peyer’s patch and in lamina propria was shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch in Peyer’s patch was investigated. IgA plasma cells in lamina propria were observed by immunohistochemical staining. Specific IgA antibodies to Candida albicans were measured with ELISA. RESULTS: From d 3 to d 14 after Candida albicans gavaging to mice, the number of Candida albicans colonizing in lumen and adhering to mucosal membrane was sharply reduced. Candida albicans translocation to mesenteric lymph nodes occurred at early time points following gavage administration and disappeared at later time points. Meanwhile, the content of specific IgA was increased obviously. Proliferation and differentiation of lymphocytes in lamina propria were also increased. CONCLUSION: Lymphocytes in lamina propria play an important role in intestinal mucosal immunity of specific-pathogen-free mice when they are first inoculated with Candida albicans. The decreasing number of Candida albicans in intestine is related to the increased level of specific IgA antibodies in the intestinal mucus. PMID:15237449

Mucosal Melanomas: A Case-Based Review of the Literature

PubMed Central

Seetharamu, Nagashree; Ott, Patrick A.

2010-01-01

Mucosal melanoma is a rare cancer that is clearly distinct from its cutaneous counterpart in biology, clinical course, and prognosis. Recent studies have shown important differences in the frequencies of various genetic alterations in different subtypes of melanoma. Activating mutations in the c-KIT gene are detected in a significant number of patients with mucosal melanoma. This observation has resulted in the initiation of several clinical trials aimed at exploring the role of receptor tyrosine kinases that inhibit c-KIT in this patient population. We herein present a comprehensive literature review of mucosal melanoma along with case vignettes of a number of pertinent cases. We further discuss melanomas of the head and neck, the female genital tract, and the anorectum, which are the three most common sites of mucosal melanoma, with a particular focus on the diagnostic, prognostic, and therapeutic data available in the literature. PMID:20571149

Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole

PubMed Central

Marty, Francisco M.; Maertens, Johan; Desai, Amit V.; Lademacher, Christopher; Engelhardt, Marc; Lu, Qiaoyang

2017-01-01

ABSTRACT Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUCave]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate. PMID:28289034

Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole.

PubMed

Kovanda, Laura L; Marty, Francisco M; Maertens, Johan; Desai, Amit V; Lademacher, Christopher; Engelhardt, Marc; Lu, Qiaoyang; Hope, William W

2017-06-01

Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUC ave ]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate. Copyright © 2017 Kovanda et al.

Effect of Bacillus subtilis and Bacillus licheniformis supplementation in diets with low- and high-protein content on ileal crude protein and amino acid digestibility and intestinal microbiota composition of growing pigs.

PubMed

Kaewtapee, Chanwit; Burbach, Katharina; Tomforde, Georgina; Hartinger, Thomas; Camarinha-Silva, Amélia; Heinritz, Sonja; Seifert, Jana; Wiltafsky, Markus; Mosenthin, Rainer; Rosenfelder-Kuon, Pia

2017-01-01

Bacillus spp. seem to be an alternative to antimicrobial growth promoters for improving animals' health and performance. However, there is little information on the effect of Bacillus spp. in combination with different dietary crude protein (CP) levels on the ileal digestibility and microbiota composition. Therefore, the objective of this study was to determine the effect of Bacillus spp. supplementation to low- (LP) and high-protein diets (HP) on ileal CP and amino acid (AA) digestibility and intestinal microbiota composition. Eight ileally cannulated pigs with an initial body weight of 28.5 kg were randomly allocated to a row-column design with 8 pigs and 3 periods of 16 d each. The assay diets were based on wheat-barley-soybean meal with two protein levels: LP (14% CP, as-fed) and HP diet (18% CP, as-fed). The LP and HP diets were supplemented with or without Bacillus spp. at a level of 0.04% (as-fed). The apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and AA was determined. Bacterial community composition from ileal digesta was analyzed by Illumina amplicon sequencing and quantitative real-time PCR. Data were analyzed as a 2 × 2 factorial design using the GLIMMIX procedures of SAS. The supplementation with Bacillus spp. did not affect both AID and SID of CP and AA in growing pigs. Moreover, there was no difference in AID of CP and AA between HP and LP diets, but SID of cystine, glutamic acid, glycine, and proline was lower ( P  < 0.05) in pigs fed the HP diets. The HP diets increased abundance of Bifidobacterium spp. and Lactobacillus spp., ( P  < 0.05) and by amplicon sequencing the latter was identified as predominant genus in microbiota from HP with Bacillus spp., whereas dietary supplementation of Bacillus spp. increased ( P  < 0.05) abundance of Roseburia spp.. The HP diet increased abundance of Lactobacillus spp. and Bifidobacterium spp.. The supplementation of Bacillus spp. resulted in a higher

Evolution of robot-assisted orthotopic ileal neobladder formation: a step-by-step update to the University of Southern California (USC) technique.

PubMed

Chopra, Sameer; de Castro Abreu, Andre Luis; Berger, Andre K; Sehgal, Shuchi; Gill, Inderbir; Aron, Monish; Desai, Mihir M

2017-01-01

To describe our, step-by-step, technique for robotic intracorporeal neobladder formation. The main surgical steps to forming the intracorporeal orthotopic ileal neobladder are: isolation of 65 cm of small bowel; small bowel anastomosis; bowel detubularisation; suture of the posterior wall of the neobladder; neobladder-urethral anastomosis and cross folding of the pouch; and uretero-enteral anastomosis. Improvements have been made to these steps to enhance time efficiency without compromising neobladder configuration. Our technical improvements have resulted in an improvement in operative time from 450 to 360 min. We describe an updated step-by-step technique of robot-assisted intracorporeal orthotopic ileal neobladder formation. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

The identification of plant lectins with mucosal adjuvant activity.

PubMed

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'Hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic.

The identification of plant lectins with mucosal adjuvant activity

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

Mucosal Vaccination for Prevention of HIV Infection and AIDS.

PubMed

Aldovini, Anna

2016-01-01

Most of HIV infections occur via the genital tract or the rectum and HIV replicates at high levels in lymphoid organs and intestinal mucosa, likely requiring a more diversified immunity than pathogens restricted to a single mucosal site, such as the gastrointestinal tract for Vibrio cholera, or the respiratory airways for the influenza virus. Numerous AIDS vaccine candidates are under development and a general observation obtained from preclinical trials in non-human primates that failed to provide sterilizing immunity is that some infection protection or delayed onset of disease is observed in the presence of anti-SIV immunity. Recent clinical trials support difficulties to reproduce in humans the results observed in simian models, but at least one of them indicated that some protection of infection can be achieved. However, given the limited efficacy observed in the RV144 trial and concerns voiced in its statistical interpretation, preclinical trials should explore more effective immunogens, whether new or as combinations of existing ones, and mucosal routes of vaccinations in addition to the systemic routes, with the goal to maximize vaccination-mediated protection. The rationale for generating both strong mucosal and systemic immunity comes from animal experiments, recent clinical trials, and other successful vaccines currently in use. Mucosal responses against SIV have been induced with a variety of SIV antigens and via different mucosal routes with a spectrum of effects on protection. This review covers the rational and the experimental data that support the validity to explore mucosal immunization for HIV infection and AIDS prevention.

Mucosal immunology

PubMed Central

Bienenstock, J.; Befus, A. D.

1980-01-01

In this review, we shall highlight some recent advances in mucosal immunology and also those concepts which seem to us to merit more attention than they normally receive. Since we cannot hope to be all inclusive, we recommend the following articles and books to the reader (Tomasi & Bienenstock, 1968; Tomasi & Grey, 1972; Bienenstock, 1974; Heremans, 1974; Mestecky & Lawton, 1974; Lamm, 1976; Tomasi, 1976; Waksman & Ozer, 1976; Porter & Knight, 1977; McGhee, Mestecky & Babb, 1978; Ogra & Dayton, 1979; Befus & Bienenstock, 1980). PMID:7002769

Glutathione metabolic status in the aged rabbit aorta.

PubMed

Lapenna, Domenico; Ciofani, Giuliano; Giamberardino, Maria Adele

2017-05-01

It is not known whether aging alters glutathione metabolic status of the mammalian arterial tissue favoring vascular oxidative stress and dysfunction. Thus we assessed total, reduced and oxidized glutathione (TG, GSH and GSSG, respectively), the glutathione redox ratio (GRR, namely [GSSG]/[GSH+2GSSG]×100), and the activities of the glutathione status-regulating enzymes glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS) and γ-glutamyl transpeptidase (γ-GT) in the aortic tissue of 9 young adult control rabbits (YACR, about 4months old) and 9 aged rabbits (AR, about 4.5years old); aortic lipid and protein oxidation and H 2 O 2 were also determined as oxidative stress indicators. Vascular function was assessed on aortic ring preparations. TG and GSH concentrations, together with γ-GCS and γ-GT activities, were significantly lower, while GSSG content and the GRR higher, in the AR than in the YACR aortas; GSSG-Red activity did not differ significantly between the two groups. Heightened levels of lipid and protein oxidation and H 2 O 2 occurred in the AR aortas, indicating age-dependent vascular oxidative stress. Moreover, in the whole population of 18 rabbits, the aortic values of GSH and related enzyme activities were inversely and significantly correlated with those of lipid and protein oxidation and H 2 O 2 , highlighting the antioxidant role of GSH and related enzymes in the vascular tissue. Aortic endothelium-dependent vasodilation was lower in the AR than in the YACR. In conclusion, glutathione metabolic status is altered in the aged rabbit aorta reflecting depressed γ-GCS- and γ-GT-related GSH biosynthesis and GSSG burden eventually favoring vascular oxidative stress and dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Amodiaquine failure associated with erythrocytic glutathione in Plasmodium falciparum malaria

PubMed Central

Zuluaga, Lina; Pabón, Adriana; López, Carlos; Ochoa, Aleida; Blair, Silvia

2007-01-01

Objective To establish the relationship between production of glutathione and the therapeutic response to amodiaquine (AQ) monotherapy in Plasmodium falciparum non-complicated malaria patients. Methodology Therapeutic response to AQ was evaluated in 32 patients with falciparum malaria in two townships of Antioquia, Colombia, and followed-up for 28 days. For every patient, total glutathione and enzymatic activity (glutathione reductase, GR, and γ-glutamylcysteine synthetase, γ-GCS) were determined in parasitized erythrocytes, non-infected erythrocytes and free parasites, on the starting day (day zero, before ingestion of AQ) and on the day of failure (in case of occurrence). Results There was found an AQ failure of 31.25%. Independent of the therapeutic response, on the starting day and on the day of failure, lower total glutathione concentration and higher GR activities in parasitized erythrocytes were found, compared with non-infected erythrocytes (p < 0.003). In addition, only on the day of failure, γ-GCS activity of parasitized erythrocytes was higher, compared with that of healthy erythrocytes (p = 0.01). Parasitized and non-parasitized erythrocytes in therapeutic failure patients (TF) had higher total glutathione on the starting day compared with those of adequate clinical response (ACR) (p < 0.02). Parasitized erythrocytes of TF patients showed lower total glutathione on the failure day, compared with starting day (p = 0.017). No differences was seen in the GR and γ-GCS activities by compartment, neither between the two therapeutic response groups nor between the two treatment days. Conclusion This study is a first approach to explaining P. falciparum therapeutic failure in humans through differences in glutathione metabolism in TF and ACR patients. These results suggest a role for glutathione in the therapeutic failure to antimalarials. PMID:17451604

Primary prevention of peri-implantitis: managing peri-implant mucositis.

PubMed

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention

Assays to Study the Interaction of Campylobacter jejuni with the Mucosal Surface.

PubMed

Clyne, Marguerite; Duggan, Gina; Dunne, Ciara; Dolan, Brendan; Alvarez, Luis; Bourke, Billy

2017-01-01

Mucosal colonization and overcoming the mucosal barrier are essential steps in the establishment of infection by Campylobacter jejuni. The interaction between C. jejuni and host cells, including binding and invasion, is thought to be the key virulence factor important for pathogenesis of C. jejuni infections in animals or humans. The intestinal mucosal barrier is composed of a polarized epithelium covered by a thick adherent mucus gel layer. There is a requirement for cell culture assays of infection to accurately represent the in vivo mucosal surface. In this chapter, we describe the use of a number of cell culture models and the use of polarized in vitro organ culture to examine the interaction of C. jejuni with mucosal surfaces.

The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

PubMed Central

Gloudemans, Anouk K.; Plantinga, Maud; Guilliams, Martin; Willart, Monique A.; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L.; Hammad, Hamida; Hoogsteden, Henk C.; Yazdanbakhsh, Maria; Hendriks, Rudi W.

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant. PMID:23527272

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

PubMed

Gloudemans, Anouk K; Plantinga, Maud; Guilliams, Martin; Willart, Monique A; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L; Hammad, Hamida; Hoogsteden, Henk C; Yazdanbakhsh, Maria; Hendriks, Rudi W; Lambrecht, Bart N; Smits, Hermelijn H

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione.

PubMed

Kaur, Amandeep; Gautam, Ruchi; Srivastava, Ritika; Chandel, Avinash; Kumar, Akhilesh; Karthikeyan, Subramanian; Bachhawat, Anand Kumar

2017-01-13

Glutathione degradation plays an important role in glutathione and redox homeostasis, and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows ∼50% sequence identity. Human and mouse ChaC2 proteins purified in vitro show 10-20-fold lower catalytic efficiency than ChaC1, although they showed comparable K m values (K m of 3.7 ± 0.4 mm and k cat of 15.9 ± 1.0 min -1 toward glutathione for human ChaC2; K m of 2.2 ± 0.4 mm and k cat of 225.2 ± 15 min -1 toward glutathione for human ChaC1). The ChaC1 and ChaC2 proteins also shared the same specificity for reduced glutathione, with no activity against either γ-glutamyl amino acids or oxidized glutathione. The ChaC2 proteins were found to be expressed constitutively in cells, unlike the tightly regulated ChaC1. Moreover, lower eukaryotes have a single member of the ChaC family that appears to be orthologous to ChaC2. In addition, we determined the crystal structure of yeast ChaC2 homologue, GCG1, at 1.34 Å resolution, which represents the first structure of the ChaC family of proteins. The catalytic site is defined by a fortuitous benzoic acid molecule bound to the crystal structure. The mechanism for binding and catalytic activity of this new enzyme of glutathione degradation, which is involved in continuous but basal turnover of cytosolic glutathione, is proposed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-08-01

One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed Central

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-01-01

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis. PMID:16173332

Comparative ileal amino acid digestibility of distillers' grains for growing pigs.

PubMed

Adeola, Olayiwola; Ragland, Darryl

2016-12-01

The objective of the experiment reported here was to investigate and compare the amino acid (AA) digestibility of distillers' dried grains (DDG), distillers' dried grains with solubles (DDGS), high protein distillers' dried grains (HP-DDG), and high protein distillers' dried grains with solubles (HP-DDGS) in growing pigs. Five semi-purified diets consisting of DDG, DDGS, HP-DDG, HP-DDGS, and nitrogen-free diet (NFD) were fed to pigs fitted with simple T-cannula for 5 observations per diet. Endogenous losses of AA at the terminal ileum of pigs that received the NFD were used to calculate standardized ileal digestibility (SID) of AA from apparent ileal digestibility (AID) of AA. The AID of Lys in DDGS was lower ( P  < 0.05) than that in DDG, which was also lower ( P  < 0.05) than that in HP-DDG. There were no differences in AID of Met among DDG, DDGS and HP-DDGS, but was greater ( P  < 0.05) in HP-DDG than in DDG or DDGS. The AID of Thr in HP-DDG was greater ( P  < 0.05) than that in DDGS but not different from that in DDG or HP-DDGS. The branched-chain AA Ile and Leu had greater ( P  < 0.05) AID in HP-DDG than in DDG, DDGS or HP-DDGS, and there was no difference among DDG, DDGS, and HP-DDGS. The AID of Trp in DDG and DDGS or HP-DDG and HP-DDGS were not different, but the AID of Trp in HP-DDGS was greater ( P  < 0.05) than that of DDGS. The greatest SID of the indispensable AA was in HP-DDG. Except for Arg and Lys in which DDG had greater ( P  < 0.05) digestibility, there was no difference between DDG and DDGS in the SID of the indispensable AA. The SID of Lys in DDG was greater ( P  < 0.05) than that of DDGS but there was no difference between that of DDG and HP-DDGS. Only His, Ile, and Met had lower ( P  < 0.05) SID in HP-DDGS than HP-DDG within the indispensable AA. The SID of Ala, Asp, Cys, Glu, Gly, Ser and Tyr were lower ( P  < 0.05) in DDGS than in HP-DDG. There SID of dispensable AA in DDG was not different from that of HP-DDGS. The

Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing high-dose chemotherapy.

PubMed

Martinez, José Manuel; Pereira, Dulcineia; Chacim, Sérgio; Mesquita, Edgar; Sousa, Inês; Martins, Ângelo; Azevedo, Teresa; Mariz, José Mário

2014-09-01

This study intends to provide new insights into the incidence and care of mucositis by the epidemiological characterization of patients with hematological malignancy treated at our institution. It also aims to understand the effectiveness of several treatments used. This is a longitudinal observational single-center study-convenience sample-which includes malignant hematologic inpatients submitted to high-dose CT from February to August 2012. We registered epidemiological data, diagnosis, oral mucositis daily questionnaire (OMDQ), World Health Organization (WHO) oral toxicity scale, and supportive medications used for mucositis. We evaluated 30 patients who had 73 episodes of hospitalization, having recorded the development of mucositis in 21.9 % (n = 16) episodes (22 patients with acute leukemia (AL) and 8 patients with non-Hodgkin lymphoma (NHL)). Grades 3-4 mucositis was reported in 4.1 % of the total episodes. The results of OMDQ showed some limitations in the quality of life, of patients with mucositis, related with the ability to eat and drink due to mouth pain (p < 0.001). In patients with NHL and AL, neutropenia entails an increased risk of mucositis (p < 0.001). Patients who did not initiate early prophylaxis with conservative measures developed mucositis earlier (p < 0.05). The incidence of mucositis is high, being reported mainly in AL patients, with limitations in quality of life. Grade 4 neutropenia increases mucositis risk. Early prophylaxis with basic oral care may delay mucositis. Further studies are crucial to characterize mucositis epidemiology, physiopathology, and its management.

Glutathione suppresses the enzymatic and non-enzymatic browning in grape juice.

PubMed

Wu, Shengjun

2014-10-01

Browning tends to occur in grape juice during processing and storage and decreases the commercial value of it. Thus, browning inhibition is an important objective for manufacturers. This study aims to investigate the efficacy of glutathione as a browning inhibitor for use on grape juice. Grape juice browning treated with glutathione was monitored during processing and accelerated browning. 0.04% of glutathione inhibited 99.4% of the polyphenoloxidase activity in the grape juice. Consequently, during processing at room temperature and accelerated browning at 80 °C, the browning in the grape juice treated with glutathione was significantly lower than that in the control (p<0.05). The results indicate that glutathione is a promising browning inhibitor used in grape juice. Copyright © 2014 Elsevier Ltd. All rights reserved.

Technical note: assessment of recovery site of mobile nylon bags for measuring ileal digestibility of starch in dairy cows.

PubMed

Norberg, E; Volden, H; Harstad, O M

2007-01-01

The objective of this study was to evaluate recovery site of mobile nylon bags for measuring ileal digestibility of ruminally undegraded starch in dairy cows. Eight feed samples of untreated and treated concentrates were examined. Three lactating cows equipped with rumen fistula and duodenal and ileal cannulas were used in the experiment. The mobile nylon bags containing intact feeds or residues after a 12-h ruminal incubation were pretreated using a 2-step procedure to simulate abomasal digestion before insertion through the duodenal cannula. To assess the effect of hindgut fermentation on starch digestibility, approximately half of the bags were collected from the ileum and half from the feces. The results indicate that feed samples should be preincubated in rumen before insertion into duodenum, and that samples with relatively high fractions of rumen-undigestible starch should be collected from the ileum instead of from feces.

Multiscale modelling approach combining a kinetic model of glutathione metabolism with PBPK models of paracetamol and the potential glutathione-depletion biomarkers ophthalmic acid and 5-oxoproline in humans and rats.

PubMed

Geenen, Suzanne; Yates, James W T; Kenna, J Gerry; Bois, Frederic Y; Wilson, Ian D; Westerhoff, Hans V

2013-06-01

A key role of the antioxidant glutathione is detoxification of chemically reactive electrophilic drug metabolites within the liver. Therefore glutathione depletion can have severe toxic consequences. Ophthalmic acid and 5-oxoproline are metabolites involved in glutathione metabolism, which can be measured readily in the blood and urine and have been proposed as candidate biomarkers of hepatic glutathione content. However, currently it is unclear whether their concentrations in plasma exhibit a robust correlation with hepatic glutathione content. To explore this important question, we have developed a novel approach which combines a physiologically based pharmacokinetic (PBPK) model of metabolism and disposition of paracetamol (acetaminophen) with a previously developed mathematical systems model of hepatic glutathione homeostasis. Paracetamol is metabolised to reactive intermediates which deplete glutathione and cause toxicity when given at high doses. Our model correctly predicted that hepatic glutathione depletion following paracetamol administration resulted in elevated concentrations of 5-oxoproline and ophthalmic acid in blood and of 5-oxoproline in urine. However, we also found from the model that concentrations of both of the compounds were likely to be influenced by prolonged administration of paracetamol and by the concentrations of intracellular metabolites such as methionine. We conclude that care must be taken when extrapolating from concentrations of these biomarkers to hepatic glutathione status.

Mucosal Immunology of Food Allergy

PubMed Central

Berin, M. Cecilia; Sampson, Hugh A.

2013-01-01

Food allergies are increasing in prevalence at a higher rate than can be explained by genetic factors, suggesting a role for as yet unidentified environmental factors. In this review, we summarize the state of knowledge about the healthy immune response to antigens in the diet and the basis of immune deviation that results in IgE sensitization and allergic reactivity to foods. The intestinal epithelium forms the interface between the external environment and the mucosal immune system, and emerging data suggest that the interaction between intestinal epithelial cells and mucosal dendritic cells is of particular importance in determining the outcome of immune responses to dietary antigens. Exposure to food allergens through non-oral routes, in particular through the skin, is increasingly recognized as a potentially important factor in the increasing rate of food allergy. There are many open questions on the role of environmental factors such as dietary factors and microbiota in the development of food allergy, but data suggest that both have an important modulatory effect on the mucosal immune system. Finally, we discuss recent developments in our understanding of immune mechanisms of clinical manifestations of food allergy. New experimental tools, particularly in the field of genomics and microbiome, are likely to shed light on factors responsible for the growing clinical problem of food allergy. PMID:23660362

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

PubMed Central

Matoba, Nobuyuki; Magérus, Aude; Geyer, Brian C.; Zhang, Yunfang; Muralidharan, Mrinalini; Alfsen, Annette; Arntzen, Charles J.; Bomsel, Morgane; Mor, Tsafrir S.

2004-01-01

A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and GM1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery. PMID:15347807

Current and Future Targets for Mucosal Healing in Inflammatory Bowel Disease

PubMed Central

Atreya, Raja; Neurath, Markus F.

2017-01-01

The induction and subsequent maintenance of mucosal healing has emerged as one of the central therapeutic goals in the management of patients with inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). Current and novel treatment options are assessed regarding their therapeutic efficacy on the basis of their ability to induce mucosal healing. However, there is still substantial debate about the precise definition of mucosal healing. Here, we will give an overview regarding the definitions of mucosal healing as well as its probable effects on long-term disease behavior and finally focus on current and potential therapeutic targets to achieve this therapeutic goal in IBD patients. PMID:28612022

Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

PubMed

Zadeh-Tahmasebi, Melika; Duca, Frank A; Rasmussen, Brittany A; Bauer, Paige V; Côté, Clémence D; Filippi, Beatrice M; Lam, Tony K T

2016-04-15

Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Feedback inhibition by thiols outranks glutathione depletion: a luciferase-based screen reveals glutathione-deficient γ -ECS and glutathione synthetase mutants impaired in cadmium-induced sulfate assimilation

PubMed Central

Jobe, Timothy O.; Sung, Dong-Yul; Akmakjian, Garo; Pham, Allis; Komives, Elizabeth A.; Mendoza-Cózatl, David G.; Schroeder, Julian I.

2015-01-01

Summary Plants exposed to heavy metals rapidly induce changes in gene expression that activate and enhance detoxification mechanisms, including toxic-metal chelation and the scavenging of reactive oxygen species. However, the mechanisms mediating toxic heavy metal-induced gene expression remain largely unknown. To genetically elucidate cadmium-specific transcriptional responses in Arabidopsis, we designed a genetic screen based on the activation of a cadmium-inducible reporter gene. Microarray studies identified a high-affinity sulfate transporter (SULTR1;2) among the most robust and rapid cadmium-inducible transcripts. The SULTR1;2 promoter (2.2 kb) was fused with the firefly luciferase reporter gene to quantitatively report the transcriptional response of plants exposed to cadmium. Stably transformed luciferase reporter lines were ethyl methanesulfonate (EMS) mutagenized, and stable M2 seedlings were screened for an abnormal luciferase response during exposure to cadmium. The screen identified non-allelic mutant lines that fell into one of three categories: (i) super response to cadmium (SRC) mutants; (ii) constitutive response to cadmium (CRC) mutants; or (iii) non-response and reduced response to cadmium (NRC) mutants. Two nrc mutants, nrc1 and nrc2, were mapped, cloned and further characterized. The nrc1 mutation was mapped to the γ-glutamylcysteine synthetase gene and the nrc2 mutation was identified as the first viable recessive mutant allele in the glutathione synthetase gene. Moreover, genetic, HPLC mass spectrometry, and gene expression analysis of the nrc1 and nrc2 mutants, revealed that intracellular glutathione depletion alone would be insufficient to induce gene expression of sulfate uptake and assimilation mechanisms. Our results modify the glutathione-depletion driven model for sulfate assimilation gene induction during cadmium stress, and suggest that an enhanced oxidative state and depletion of upstream thiols, in addition to glutathione

Extraction of glutathione from EFB fermentation waste using methanol with sonication process

NASA Astrophysics Data System (ADS)

Muryanto, Muryanto; Alvin, Nurdin, Muhammad; Hanifah, Ummu; Sudiyani, Yanni

2017-11-01

Glutathione is important compound on the human body. Glutathione have a widely use at pharmacy and cosmetics as detoxification, skin whitening agent, antioxidant and many other. This study aims to obtain glutathione from Saccharomyces cerevisiae in fermentation waste of second generation bioethanol. The remaining yeast in the empty fruit bunch (EFB) fermentation was separated from the fermentation solution use centrifugation process and then extracted using a methanol-water solution. The extraction process was done by maceration which was assisted by sonication process. Solvent concentration and time of sonication were varied to see its effect on glutathione concentration. The concentration of glutathione from the extraction process was analyzed using alloxan method with UV-Vis spectrophotometer. The results show that the highest glutathione concentration was approximately 1.32 g/L obtained with methanol solvent at 90 minutes of maceration following with 15 minutes sonication.

Orthotopic sigmoid vs. ileal neobladders in Japanese patients: a comparative assessment of complications, functional outcomes, and quality of life.

PubMed

Miyake, Hideaki; Furukawa, Junya; Sakai, Iori; Muramaki, Mototsugu; Yamashita, Masuo; Inoue, Taka-Aki; Fujisawa, Masato

2013-10-01

To compare the clinical outcomes of sigmoid and ileal neobladders (NBs) created following radical cystectomy. This study included 90 and 144 Japanese patients undergoing radical cystectomy and orthotopic NB reconstruction with a sigmoid and ileal segment, respectively. Postoperative clinical outcomes between the sigmoid and ileal NB groups (SNBG and INBG) were compared. In this series, 110 early and 51 late complications occurred in 71 and 41 patients, respectively; however, there was no significant difference in the incidence of complications between SNBG and INBG. At 1 year postoperatively, there were no significant differences in the proportion of spontaneous voiders and the continence status between these 2 groups; however, despite the lack of significant differences in the maximal flow rate and voided volume, the post-void residual in SNBG was significantly smaller than that in INBG. Voiding functional outcomes at 5 years postoperatively were also obtained from 28 and 49 in SNBG and INBG, respectively. Although there were no significant changes in the functional outcomes in SNBG, the proportion of spontaneous voiders and post-void residual in INBG at 5 years postoperatively were significantly poorer than those at 1 year postoperatively. Furthermore, the postoperative health-related quality of life assessed by a Short-Form 36 survey did not show any significant differences in all 8 scores between these 2 groups. Both types of NB reconstruction resulted in comparatively satisfactory outcomes; however, the voiding function, particularly that on long-term follow-up, in SNBG appeared to be more favorable than that in INBG. Copyright © 2013 Elsevier Inc. All rights reserved.

A comparative study of lingual mucosal graft urethroplasty with buccal mucosal graft urethroplasty in urethral stricture disease: An institutional experience

PubMed Central

Pal, Dilip Kumar; Gupta, Depak Kumar; Ghosh, Bastab; Bera, Malay Kumar

2016-01-01

Aims: A prospective study to compare the outcomes of lingual versus buccal mucosal graft urethroplasty in patients with long segment anterior urethral strictures disease. Materials and Methods: The study included 30 patients for buccal mucosal graft urethroplasty (group I) and 30 patients for lingual mucosal graft urethroplasty (group II) for treatment of long segment (>3 cm) incomplete anterior urethral stricture disease using single-stage dorsal onlay free oral mucosal graft urethroplasty by Barbagli's technique between February 2013 to September 2014. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Results: The results of urethroplasty in between two group were not significant (P > 0.05) in terms of Qmax (P = 0.63), mean postoperative AUA symptom score (P = 0.83), operative time (P = 0.302) intra operative blood loss (P = 0.708), duration of postoperative hospitalization (P = 0.83), but slurring of speech complications was seen in group II, but not in group I. Long-term complications of salivary disturbance, tightness of the mouth, persistent pain at graft site, perioral numbness, seen only in group I (BMGU). Conclusion: LMG urethroplasty is an excellent alternative to BMG urethroplasty with comparable results of urethroplasty and minimal donor site complications. PMID:27141184

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation

PubMed Central

Heron, Samantha E.; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to “inflammaging” that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation.

PubMed

Heron, Samantha E; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to "inflammaging" that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore

Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model.

PubMed

Sobue, T; Bertolini, M; Thompson, A; Peterson, D E; Diaz, P I; Dongari-Bagtzoglou, A

2018-06-01

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix. Treatment of organotypic constructs with 5-fluorouracil (5-FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three-dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5-FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E-cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5-FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5-FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Checkpoint inhibition for advanced mucosal melanoma.

PubMed

Thierauf, Julia; Veit, Johannes A; Hess, Jochen; Treiber, Nicolai; Lisson, Catharina; Weissinger, Stephanie E; Bommer, Martin; Hoffmann, Thomas K

2017-04-01

Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage. Expression of PD-L1 and PD-1 in all tumour samples was evaluated immunohistochemically. All patients received at least two cycles of nivolumab or pembrolizumab. The most severe adverse events were categorised as CTCAE (common terminology criteria for adverse events) Grade 2. All patients showed progressive disease after restaging at three and six months, and no partial or complete response was observed. Immunohistochemical staining demonstrated PD-L1 expression in less than 5% of tumour cells. Systemic therapy with either nivolumab or pembrolizumab showed no clinical response, however, tumour progression was identified in all patients using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune-related response criteria (irRC) to evaluate tumour response.

Oral and intestinal mucositis - causes and possible treatments.

PubMed

Duncan, M; Grant, G

2003-11-01

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are

Rebamipide gargle in preventive management of chemo-radiotherapy induced oral mucositis.

PubMed

Chaitanya, B; Pai, Keerthilatha M; Yathiraj, Prahlad H; Fernandes, Donald; Chhaparwal, Yogesh

2017-09-01

Oral mucositis is inflammation of mucosa of oral cavity which is an inevitable and acute side effect in patients undergoing chemoradiotherapy for head & neck cancer. Though many agents have been tried in prevention & treatment of oral mucositis, until date no single agent exists that is universally established to be effective. 60 Patients diagnosed with Head & Neck cancer recruited for concurrent chemo-radiotherapy were assigned in a double blind fashion into 2 groups using computer based 1:1 ratio randomization. Subjects in Group 1 were given Rebamipide gargle while subjects in Group 2 were given Placebo gargle in similar colour coded bottles to gargle 6 times/day. Subjective assessment of oral mucositis was done by Numeric Rating Scale (NRS) and objective scoring according to RTOG system. All subjects in the Group 1 reported good treatment compliance but 4 subjects in Group 2 developed burning sensation to gargle and were excluded. Onset of oral mucositis was 3.5days earlier in Group 2 (mean=11.17) as compared to Group 1 (mean=14.63). At the end of chemo-radiotherapy, severity of oral mucositis was significantly lower in Group 1 (mean=1.97) than in Group 2 (mean=2.81). Findings of this study revealed that Rebamipide gargle may be an effective means to prolong the onset of oral mucositis and may reduce the severity of oral mucositis in undergoing chemo-radiotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum

PubMed Central

Friedman, James; Alam, S. Munir; Shen, Xiaoying; Xia, Shi-Mao; Stewart, Shelley; Anasti, Kara; Pollara, Justin; Fouda, Genevieve G.; Yang, Guang; Kelsoe, Garnett; Ferrari, Guido; Tomaras, Georgia D.; Haynes, Barton F.; Liao, Hua-Xin

2012-01-01

Background Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. Methods We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). Results The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. Conclusions These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces. PMID:22624058

Health-Related Quality of Life after Radical Cystectomy for Bladder Cancer in Elderly Patients with Ileal Orthotopic Neobladder or Ileal Conduit: Results from a Multicentre Cross-Sectional Study Using Validated Questionnaires.

PubMed

Cerruto, Maria Angela; D'Elia, Carolina; Siracusano, Salvatore; Saleh, Omar; Gacci, Mauro; Cacciamani, Giovanni; De Marco, Vincenzo; Porcaro, Antonio Benito; Balzarro, Matteo; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Serni, Sergio; Carini, Marco; Verze, Paolo; Artibani, Walter

2018-01-01

To evaluate health-related quality of life (HR-QoL) outcomes in elderly patients with different type of urinary diversion (UD), ileal conduit (IC) and ileal orthotopic neobladder (IONB), after radical cystectomy (RC) for bladder cancer, by using validated self-reported cancer-specific instruments. We retrospectively reviewed 77 patients who received an IC or an IONB after RC. HR-QoL was assessed with specific and validated disease questionnaires, administered at last follow-up. At univariate analysis, at a mean follow-up of 60.91 ± 5.63 months, IONB results were favourable with regard to the following HR-QoL aspects: nausea and vomiting (p = 0.045), pain (p = 0.049), appetite loss (p = 0.03), constipation (p = 0.000), financial impact (p = 0.012) and cognitive functioning (p = 0.000). This last functional aspect was significantly worse in female patients (p = 0.029). Emotional functioning was significantly better in patients without long-term complications (p = 0.016). At multivariate analysis, male gender and IONB were independent predictors of better cognitive functioning, while long-term complications negatively affected emotional functioning. Obtained results suggest that an IONB can also be suitable for elderly patients compared with an IC with few and selected advantages in favour of the former UD. Preoperative patient's selection, counselling, education and active participation in the decision-making process lead to a more suitable choice of treatment. © 2018 S. Karger AG, Basel.

Strategies of immunization against mucosal infections.

PubMed

Russell, M W; Martin, M H; Wu, H Y; Hollingshead, S K; Moldoveanu, Z; Mestecky, J

2000-12-08

The presence of secretory (S-) IgA in middle-ear fluid and localization of IgA-secreting cells in its mucosae suggest that the middle ear is an effector site of the mucosal immune system. Several strategies have been devised to induce potent, long-lasting, and recallable mucosal S-IgA antibodies, as well as circulating IgG antibodies and Th1- or Th2-type help, according to the most appropriate responses for a particular infection. Application of immunogens to inductive sites in the upper respiratory tract may be most effective for generating responses in the middle ear and nasopharynx for protection against the organisms responsible for otitis media.

Glutathione metabolism as a determinant of therapeutic efficacy: a review.

PubMed

Arrick, B A; Nathan, C F

1984-10-01

Glutathione, as the chief nonprotein intracellular sulfhydryl, affects the efficacy and interactions of a variety of antineoplastic interventions, mainly through nucleophilic thioether formation or oxidation-reduction reactions. Thus, glutathione plays a role in the detoxification and repair of cellular injury by such diverse agents as mechlorethamine, melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, and mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone). Glutathione may play a similar role in host and tumor cell responses to radiation, hyperthermia, and the reactive reduction products of oxygen secreted by inflammatory cells. Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate. It seems likely that alterations in glutathione metabolism of tumor or host as a result of one therapeutic intervention may affect the outcome of concurrent treatments. Knowledge of these interactions may be useful in designing combination therapy for neoplastic disease.

Expression of glutathione peroxidase I gene in selenium-deficient rats.

PubMed Central

Reddy, A P; Hsu, B L; Reddy, P S; Li, N Q; Thyagaraju, K; Reddy, C C; Tam, M F; Tu, C P

1988-01-01

We have characterized a cDNA pGPX1211 encoding rat glutathione peroxidase I. The selenocysteine in the protein corresponded to a TGA codon in the coding region of the cDNA, similar to earlier findings in mouse and human genes, and a gene encoding the formate dehydrogenase from E. coli, another selenoenzyme. The rat GSH peroxidase I has a calculated subunit molecular weight of 22,155 daltons and shares 95% and 86% sequence homology with the mouse and human subunits, respectively. The 3'-noncoding sequence (greater than 930 bp) in pGPX1211 is much longer than that of the human sequences. We found that glutathione peroxidase I mRNA, but not the polypeptide, was expressed under nutritional stress of selenium deficiency where no glutathione peroxidase I activity can be detected. The failure of detecting any apoprotein for the glutathione peroxidase I under selenium deficiency and results published from other laboratories supports the proposal that selenium may be incorporated into the glutathione peroxidase I co-translationally. Images PMID:2838821

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

PubMed

van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

2014-11-01

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer. © 2014 John Wiley & Sons Ltd.

Treatment of chemotherapy-induced oral mucositis with light-emitting diode.

PubMed

Corti, Luigi; Chiarion-Sileni, Vanna; Aversa, Savina; Ponzoni, Alberto; D'Arcais, Raimondo; Pagnutti, Stefano; Fiore, Davide; Sotti, Guido

2006-04-01

The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer. Mucositis occurs in more than 40% of chemotherapy-treated patients, significantly reducing the quality of their lives. Many different interventions have been evaluated to reduce oral mucositis. Recently, good results have been achieved by phototherapy with photoradiation, a technique which has virtually no side effects. Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes (LEDs) may be effective. However, until now, no studies have been available on this subject. Twelve patients, aged from 34 to 82, selected on the basis of a diagnosis of chemotherapy-induced oral mucositis, were treated intra-orally through a noncoherent LED emission, wavelength 645 +/- 15 nm, 7.8 mW, fluence 0.99 J/cm(2), three times a day for 1 week. Mucositis was scored daily using the Daily Mucositis Index (DMI), a scale that evaluates the disease evolution through 16 different items. The primary end-point assessed was the time to recovery, from the start of LED treatment, compared to a nonrandomized control group of 12 patients with comparable stomatitis. The median healing time, expressed as the DMI decrease, was 1.7 (range 1-2.8) and, in seven LED-treated patients, was shorter than in the control group. The healing rate (measured as the ratio of the DMIs) increased from 117% to 164%. This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis. This result needs to be confirmed in an adequate phase III study.

Effect of glutathione during bottle storage of sparkling wine.

PubMed

Webber, Vanessa; Dutra, Sandra Valduga; Spinelli, Fernanda Rodrigues; Carnieli, Gilberto João; Cardozo, Alejandro; Vanderlinde, Regina

2017-02-01

Reduced glutathione (GSH) is an efficient antioxidant on limiting browning, losing varietal aromas and off-flavor formation. Therefore, this study aims to evaluate the effect of GSH addition (10, 20 and 30mgL(-1)) after the disgorging of the sparkling wine during storage. The sparkling wines were analyzed at 1, 6, 12 and 18months of storage according to the color index, concentration of the free SO2, phenolic compounds, catechin, epicatechin, caffeic acid, coumaric acid, acetaldehyde, total and reduced glutathione. The results show that GSH concentration decreased to the level of the control sparkling wine during the first 6months, and the total glutathione gradually declined up to 12months. The GSH reduces browning and acetaldehyde formation for up to 12months. However, the presence of glutathione had low or no influence on the concentration of free SO2, total phenolics, catechin, epicatechin, caffeic and coumaric acids. Copyright © 2016 Elsevier Ltd. All rights reserved.

KIT amplification and gene mutations in acral/mucosal melanoma in Korea.

PubMed

Yun, Jina; Lee, Jeeyun; Jang, Jiryeon; Lee, Eui Jin; Jang, Kee Taek; Kim, Jung Han; Kim, Kyoung-Mee

2011-06-01

Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720A>G) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population. © 2011 The Authors. APMIS © 2011 APMIS.

Surgical treatment of ulcerative colitis: ileorectal vs ileal pouch-anal anastomosis.

PubMed

Scoglio, Daniele; Ahmed Ali, Usama; Fichera, Alessandro

2014-10-07

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk.

Polymorphisms of glutathione S-transferase Mu 1, glutathione S-transferase theta 1 and glutathione S-transferase Pi 1 genes in Hodgkin's lymphoma susceptibility and progression.

PubMed

Lourenço, Gustavo J; Néri, Iramaia A; Sforni, Vitor C S; Kameo, Rodolfo; Lorand-Metze, Irene; Lima, Carmen S P

2009-06-01

We tested in this study whether the polymorphisms of the glutathione S-transferase Mu1 (GSTM1), glutathione S-transferase Theta 1 (GSTT1) and glutathione S-transferase Pi 1 (GSTP1), involved in metabolism of chemical agents, cell proliferation and cell survival, alter the risk for Hodgkin lymphoma (HL). Genomic DNA from 110 consecutive patients with HL and 226 controls was analysed by polymerase chain reaction and restriction digestion for the polymorphism analyses. Similar frequencies of the GSTM1 and GSTT1 genotypes were seen in patients and controls. In contrast, the frequency of the GSTP1 wild genotype (59.1%versus 36.3%, P = 0.004) was higher in patients than in controls. Individuals with the wild genotype had a 2.68 (95%CI: 1.38-5.21)-fold increased risk for the disease than others. An excess of the GSTP1 wild genotype was also observed in patients with tumors of stages III + IV when compared with those with tumors of stages I + II (39.1%versus 20.0%, P = 0.03). These results suggest that the wild allele of the GSTP1 gene is linked to an increased risk and high aggressiveness of the HL in our cases but they should be confirmed by further studies with larger cohorts of patients and controls.

Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus cholera toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity.

PubMed

Maeto, Cynthia; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, María Magdalena

2014-01-01

Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after their mucosal administration in DNA prime/MVA boost intranasal regimes, defining the cooperation of both adjuvants to enhance immune responses against the HIV-1 Env antigen. Our results demonstrated that nasal mucosal DNA/MVA immunization schemes can be effectively improved by the co-delivery of DNA-IL-12 plus CTB inducing elevated HIV-specific CD8 responses in spleen and more importantly in genital tract and genito-rectal draining lymph nodes. Remarkably, these CTL responses were of superior quality showing higher avidity, polyfunctionality and a broader cytokine profile. After IL-12+CTB co-delivery, the cellular responses induced showed an enhanced breadth recognizing with higher efficiency Env peptides from different subtypes. Even more, an in vivo CTL cytolytic assay demonstrated the higher specific CD8 T-cell performance after the IL-12+CTB immunization showing in an indirect manner its potential protective capacity. Improvements observed were maintained during the memory phase where we found higher proportions of specific central memory and T memory stem-like cells T-cell subpopulations. Together, our data show that DNA-IL-12 plus CTB can be effectively employed acting as mucosal adjuvants during DNA prime/MVA boost intranasal vaccinations, enhancing magnitude and quality of HIV-specific systemic and mucosal immune responses.

Saccharomyces boulardii upgrades cellular adaptation after proximal enterectomy in rats

PubMed Central

Buts, J; De Keyser, N; Marandi, S; Hermans, D; Sokal, E; Chae, Y; Lambotte, L; Chanteux, H; Tulkens, P

1999-01-01

BACKGROUND—Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa.
AIMS—To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats.
METHODS—Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days. The effects on ileal mucosal adaptation were assessed eight days after surgery.
RESULTS—Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase. Treatment of resected animals with S boulardii had no effect on mucosal hyperplasia but did upgrade disaccharidase activities to the levels of the transected group. Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity and mucosal polyamine concentrations. Likewise, sodium dependent D-glucose uptake by brush border membrane vesicles, measured as a function of time and glucose concentration in the incubation medium, was significantly (p<0.05) increased by 81% and three times respectively in the resected group treated with S boulardii. In agreement with this, expression of the sodium/glucose cotransporter-1 in brush border membranes of resected rats treated with S boulardii was enhanced twofold compared with resected controls.
CONCLUSION—Oral administration of S boulardii soon after proximal enterectomy improves functional adaptation of the remnant ileum.


Keywords: Saccharomyces boulardii; intestine; adaptation; polyamines; brush border membrane enzymes; glucose uptake PMID:10369710

Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1.

PubMed

Cooke, R J; Björnestedt, R; Douglas, K T; McKie, J H; King, M D; Coles, B; Ketterer, B; Mannervik, B

1994-09-01

The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher levels of radioisotope incorporation for the Mu than the Alpha families. Taking rat GST 3-3, 1.18 (+/- 0.05) mol of radiolabel from S-(2-nitro-4-azidophenyl)glutathione was incorporated per mol of dimeric enzyme, which could be blocked by the presence of the strong competitive inhibitor, S-tritylglutathione (Ki = 1.4 x 10(-7) M). Radiolabelling of the protein paralleled the loss of enzyme activity. Photoaffinity labelling by tritiated S-(2-nitro-4-azidophenyl)glutathione on a preparative scale (in the presence and absence of S-tritylglutathione) followed by tryptic digestion and purification of the labelled peptides indicated that GST 3-3 was specifically photolabelled; the labelled peptides were sequenced. Similarly, preparative photoaffinity labelling by S-(2-nitro-4-azidophenyl)glutathione of the rat liver 1-1 isoenzyme, the human GST A1-1 and the human-rat chimaeric GST, H1R1/1, was carried out with subsequent sequencing of radiolabelled h.p.l.c.-purified tryptic peptides. The results were interpreted by means of molecular-graphics analysis to locate photoaffinity-labelled peptides using the X-ray-crystallographic co-ordinates of rat GST 3-3 and human GST A1-1. The molecular-graphical analysis indicated that the labelled peptides are located within the immediate vicinity of the region occupied by S-substituted glutathione derivatives bound in the active-site cavity of the GSTs investigated.

Reactions of benzene oxide with thiols including glutathione.

PubMed

Henderson, Alistair P; Barnes, Martine L; Bleasdale, Christine; Cameron, Richard; Clegg, William; Heath, Sarah L; Lindstrom, Andrew B; Rappaport, Stephen M; Waidyanatha, Suramya; Watson, William P; Golding, Bernard T

2005-02-01

S-Phenylmercapturic acid is a minor metabolite of benzene used as a biomarker for human benzene exposures. The reaction of intracellular glutathione with benzene oxide-oxepin, the initial metabolite of benzene, is presumed to give 1-(S-glutathionyl)-cyclohexa-3,5-dien-2-ol, which undergoes dehydration to S-phenylglutathione, the precursor of S-phenylmercapturic acid. To validate the proposed route to S-phenylglutathione, reactions of benzene oxide-oxepin with glutathione and other sulfur nucleophiles have been studied. The reaction of benzene oxide with an excess of aqueous sodium sulfide, followed by acetylation, gave bis-(6-trans-5-acetoxycyclohexa-1,3-dienyl)sulfide, the structure of which was proved by X-ray crystallography. Reactions of benzene oxide-oxepin in a 95:5 (v/v) mixture of phosphate buffer in D2O with (CD3)2SO were monitored by 1H NMR spectroscopy. In the absence of glutathione, the half-life of benzene oxide-oxepin was ca. 34 min at 25 degrees C and pD 7.0. The half-life was not affected in the range of 2-15 mM glutathione in the presence and absence of a commercial sample of human glutathione S-transferase (at pH 7.0, 8.0, 8.5, or 10.0). The adduct 1-(S-glutathionyl)-cyclohexa-3,5-diene-2-ol was identified in these reaction mixtures, especially at higher pH, by mass spectrometry and by its acid-catalyzed decomposition to S-phenylglutathione. Incubation of benzene oxide with N-acetyl-L-cysteine at 37 degrees C and pH 10.0 and subsequent mass spectrometric analysis of the mixture showed formation of pre-S-phenylmercapturic acid and the dehydration product, S-phenylmercapturic acid. The data validate the premise that benzene oxide-oxepin can be captured by glutathione to give (1R,2R)- and/or (1S,2S)-1-(S-glutathionyl)-cyclohexa-3,5-dien-2-ol, which dehydrate to S-phenylglutathione. The capture is a relatively inefficient process at pH 7 that is accelerated at higher pH. These studies account for the observation that the metabolism of benzene is

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. Whenmore » wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.« less

Phosphorus utilization and characterization of ileal digesta and excreta from broiler chickens fed diets varying in cereal grain, phosphorus level, and phytase addition.

PubMed

Leytem, A B; Widyaratne, G P; Thacker, P A

2008-12-01

Both intrinsic and exogenous phytase in poultry feeds can alter phytate utilization and the solubility of P excreted. This experiment determined the effects of feeding diets varying in cereal grain, P concentration and phytase addition on phytate and P utilization and P characterization of ileal digesta and excreta. Twelve treatments, consisting of diets based on corn, wheat, barley, or high fat-low lignin oat and 3 P treatments (low P with 0.30% nonphytate P; low P + 1,000 phytase units of phytase; high P with 0.45% nonphytate P), were fed to 300 broilers using a factorial design. Fresh excreta were collected at 20 and 21 d and ileal digesta was collected at 21 d. Ileal digesta and excreta were analyzed for total P, phytate P and Ca, with P composition determined by solution (31)P nuclear magnetic resonance spectroscopy. Excreta samples were also analyzed for water soluble P (WSP). Apparent ileal digestibility coefficients for phytate P and total P ranged from 0.03 to 0.42 and 0.56 to 0.71, respectively. Diets supplemented with phytase had greater phytate P hydrolysis than unsupplemented diets. Apparent total tract digestibility coefficients for phytate P and total P ranged from 0.10 to 0.73 and 0.43 to 0.61, respectively. Across cereal grains, there was almost a 3-fold increase in total tract phytate P hydrolysis with phytase supplementation. The P composition of ileal digesta was predominantly phytate P (70 to 88% of total P), whereas excreta phytate P ranged from 26 to 76% of total P. Excreta WSP ranged from 3.2 to 7.5 g kg(-1) and was least for the barley diets. There was a 25% reduction in excreta WSP from the high P to the low P + phytase diets and a 37% reduction from the high P to the low P diets. As cereal grain had little influence on phytate digestibility, it is unlikely that intrinsic phytase in grain has much influence on phytate utilization by poultry. Both total P and WSP in excreta were reduced by the low P diet and the low P + phytase diet

Induction of pneumococcal polysaccharide-specific mucosal immune responses by oral immunization.

PubMed

VanCott, J L; Kobayashi, T; Yamamoto, M; Pillai, S; McGhee, J R; Kiyono, H

1996-04-01

Liposome and cholera toxin (CT) are considered to be effective antigen delivery vehicles and adjuvants for mucosal vaccines. The effect of these antigen delivery systems on adjuvant responses to mucosally administered pneumococcal polysaccharide (Pnup) was investigated in this study. Both mucosal (e.g. oral) and systemic (i.p.) immunization of mice with purified preparations of Pnup type 23F induced antigen-specific IgM responses in sera. Interestingly, oral immunization of as little as 10 micrograms of Pnup type 23F was sufficient to induce systemic IgM responses. Pnup-specific IgM antibodies peaked by day 7 and no booster responses were evident after a second dose on day 14. In order to examine whether IgG and IgA Pnup-specific immune responses are induced by mucosal immunization, the mucosal adjuvant CT was mixed with Pnup type 23 as an oral vaccine. Co-oral administration of CT and Pnup type 23F resulted in the induction of Pnup-specific faecal IgA antibodies. These results were confirmed by detecting antigen-specific IgA-spot-forming cells in mononuclear cell suspensions prepared from the intestine of immunized mice. These findings suggest that oral immunization with Pnup in the presence of mucosal adjuvants, such as CT, could induce Pnup-specific IgA responses whereas Pnup alone did not. In an attempt to further enhance antigen-specific antibody responses, Pnup type 23F was encapsulated in liposomes and used as mucosal vaccine. However, immunogenicity of Pnup was not improved.

The trophic effect of epidermal growth factor on morphological changes and polyamine metabolism in the small intestine of rats.

PubMed

Tsujikawa, T; Bamba, T; Hosoda, S

1990-06-01

This study was undertaken to evaluate the effect of epidermal growth factor (EGF) on the morphological changes and polyamine metabolism in the atrophic small intestinal mucosa of rats caused by feeding elemental diet (ED; Elental, Ajinomoto, Tokyo) for several weeks. Four-week-old Wistar male rats were given ad libitum ED (1 kcal/ml) for 4 weeks. The body weight increased to the same extent as the control group fed a pellet diet. However, the small intestine became atrophic: the mucosal wet weight of the jejunum decreased to 70%, while that of the ileum decreased to 60%. EGF (10 micrograms/kg) was subcutaneously injected into these rats every 8 hours. Ornithine decarboxylase (ODC) activities of the jejunal and ileal mucosa rose within 12 hours of the initial EGF administration. Mucosal DNA specific activities tended to increase. Next, EGF (30 micrograms/kg/day) was intraperitoneally administered with a Mini-osmotic pump for one week. The wet weight, protein and DNA contents of the ileal mucosa increased significantly compared with those of the saline administered controls, while the crypt cell production rate (CCPR) also increased. Histologically, increases in both villus height and crypt depth were confirmed. These findings indicate that EGF causes mucosal proliferation through polyamine metabolism even in the atrophic small intestine of mature rats after ED administration for 4 weeks.

Cryopreservation of Human Mucosal Leukocytes

PubMed Central

Shu, Zhiquan; Levy, Claire N.; Ferre, April L.; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C.; Adams Waldorf, Kristina M.; Veazey, Ronald S.; Germann, Anja; von Briesen, Hagen; McElrath, M. Juliana; Dezzutti, Charlene S.; Sinclair, Elizabeth; Baker, Chris A. R.; Shacklett, Barbara L.; Gao, Dayong; Hladik, Florian

2016-01-01

Background Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. Methods and Findings To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10–15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Conclusions Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes. PMID:27232996

Cryopreservation of Human Mucosal Leukocytes.

PubMed

Hughes, Sean M; Shu, Zhiquan; Levy, Claire N; Ferre, April L; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C; Adams Waldorf, Kristina M; Veazey, Ronald S; Germann, Anja; von Briesen, Hagen; McElrath, M Juliana; Dezzutti, Charlene S; Sinclair, Elizabeth; Baker, Chris A R; Shacklett, Barbara L; Gao, Dayong; Hladik, Florian

2016-01-01

Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

Chemotherapy: the effect of oral cryotherapy on the development of mucositis.

PubMed

Karagözoğlu, Serife; Filiz Ulusoy, Mehlika

2005-07-01

The aim of this study is to investigate the effect of oral cryotherapy on the development of chemotherapy-induced mucositis in patients administered combined chemotherapy. Mucositis has been of interest to scientists for more than 20 years. Unfortunately, this has not resulted in the development of standard procedures for prevention and management. To cope with this side-effect and to prevent opportunistic infections that may emerge during treatment, attempts are taken to provide preventative and comfort measures. In this context, cryotherapy (oral cooling) has become popular as a cheap and readily applicable method in preventing the developing due the rapid infusion of chemotherapy agents, or decreasing its severity. Study involved 60 patients, 30 of whom were in the study group and 30 in the control group. Ice cubes at a size that can be moved easily in the mouth and whose corners have been smoothed in order that they will not cause irritation in the mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was initiated five minutes before chemotherapy and maintained during venous infusions of etoposide (Vepesid), platinol (Cisplatin), mitomycin (Mitomycin-C) and vinblastin (Velbe) depending on the chemotherapy course. According to Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group and 90.0% in control group, the difference between two groups being statistically significant (P < 0.05). According to Physician-Judged Mucositis Grading, the rate of mucositis is 10.0% in the study group and 50.0% in the control group, the difference between two groups being statistically significant (P < 0.05). Oral pH values decreased in 90% of the subjects in study group, i.e. mucositis risk was reduced whereas oral pH values remained unchanged or decreased in 86.7% of the subjects in the control group, namely mucositis risk increased. The difference between study and control groups in terms of the change in pH values after

Biochemotherapy in patients with advanced head and neck mucosal melanoma.

PubMed

Bartell, Holly L; Bedikian, Agop Y; Papadopoulos, Nicholas E; Dett, Tina K; Ballo, Matthew T; Myers, Jeffrey N; Hwu, Patrick; Kim, Kevin B

2008-12-01

No systemic therapy regimen has been recognized as effective for metastatic mucosal melanoma of the head and neck. We retrospectively analyzed the effectiveness of biochemotherapy in patients with advanced head and neck mucosal melanoma. We evaluated the medical records of 15 patients at our institution who had received various biochemotherapy regimens for advanced head and neck mucosal melanoma. After a median follow-up duration of 13 months, 3 patients (20%) had partial response, and 4 patients (27%) had complete response. The median time to disease progression for all 15 patients was 10 months. The median overall survival duration for all patients was 22 months. Although this was a small study, our results, especially the high complete response and overall response rates, indicate that biochemotherapy for advanced head and neck mucosal melanoma should be considered as a systemic treatment option for patients with this aggressive malignancy.

Vigilance or Subversion? Constitutive and Inducible M Cells in Mucosal Tissues.

PubMed

Lo, David D

2018-03-01

Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues. Here, I consider the unique induction requirements of each M cell subset and functional differences, highlighting the potentially distinct consequences in mucosal immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic inclusion in the diet did not alter the standardized ileal digestible tryptophan to lysine ratio for growing pigs

USDA-ARS?s Scientific Manuscript database

Two 21-d experiments were conducted to determine the optimum standard ileal digestible (SID) Trp:Lys ratio in growing pigs fed diets supplemented with or without an antibiotic. The primary response variables in both experiments were ADG, ADFI, G:F and plasma urea N (PUN) concentrations with the opti...

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

PubMed

Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Screening and referral of oral mucosal pathology: a check-up of Australian dentists.

PubMed

Allen, K; Farah, C S

2015-03-01

Oral squamous cell carcinomas and potentially malignant oral disorders can be detected early by visually inspecting the oral soft tissues. This study aimed to determine Australian dentists' opinions and practices regarding oral mucosal screening, referral and oral cancer prevention. Nine hundred and ninety-nine randomly selected general dentists were mailed a questionnaire. The questionnaire queried practitioners' opinions and perceptions of oral mucosal screening, their referral practices and their beliefs regarding detection and prevention of oral cancer. A total of n=640 individuals responded, yielding a response rate of 70.2%. Most Australian dentists reported to routinely perform oral mucosal screening. Lack of training, confidence, time and financial incentives were seen as barriers to performing mucosal screening to at least some degree by participants in this study. Most dentists manage referrals for oral mucosal pathology appropriately; however, only about half believe in following up with referred patients. Only half of dentists surveyed believed that they could influence a patient to quit smoking. Australian dentists place importance on oral mucosal screening. Some changes to dental education and training could be made to further improve confidence and ability of dentists in detecting and referring oral mucosal pathology. © 2015 Australian Dental Association.

Targeting of plant-derived vaccine antigens to immunoresponsive mucosal sites.

PubMed

Rigano, M Manuela; Sala, Francesco; Arntzen, Charles J; Walmsley, Amanda M

2003-01-30

Most pathogenic microorganisms enter their host via the mucosal surfaces lining the digestive, respiratory and urino-reproductive tracts of the body. The most efficient means of protecting these surfaces is through mucosal immunization. Transgenic plants are safe and inexpensive vehicles to produce and mucosally deliver protective antigens. However, the application of this technology is limited by the poor response of the immune system to non-particulate, subunit vaccines. Co-delivery of therapeutic proteins with targeting proteins, such as the B subunit of the Escherichia coli heat labile enterotoxin (LTB), could increase the effectiveness of such antigens.

Ileal absorption of bile acids in patients with chronic cholestasis: SeHCAT test results and effect of ursodeoxycholic acid (UDCA).

PubMed

Chazouillères, O; Marteau, P; Haniche, M; Jian, R; Poupon, R

1996-12-01

The effect of cholestasis on ileal bile acid absorption is controversial in animal models (up- or down-regulation) and unknown in humans. We therefore studied values of the selena homotaurocholic acid (SeHCAT) test before and after long-term administration (>3 months, 13-15 mg/kg/day) of ursodeoxycholic acid (UDCA) in 27 patients with chronic cholestatic liver diseases (24 women, 3 men; mean age, 50 years; 24 primary biliary cirrhosis, 2 secondary biliary cirrhosis, 2 others). The control group consisted of 14 healthy volunteers. Seven-day SeHCAT percentage retention was identical in the 12 untreated cholestatic patients (serum bilirubin, 75+/-42 micromol/L, alkaline phosphatase, 4.2+/-1.0 N; mean+/-SEM) and in the control group (43.6+/-2.9 and 43.8+/-4.2%, respectively). In the 22 patients treated by UDCA for 38+/-8 months, SeHCAT percentage retention was 20.3+/-3.0%. In the seven patients with the SeHCAT test done before and after UDCA treatment (16+/-5 months), SeHCAT percentage retention decreased significantly under UDCA therapy (42.0+/-4.4 vs 19.4+/-4.1%; P < 0.02). We conclude that, in patients with chronic cholestasis (1) SeHCAT percentage retention is not altered-taken together with the known defect of biliary excretion, this lack of increase in SeHCAT percentage retention argues against up-regulation of bile acid ileal transport; and (2) UDCA treatment induces a decrease in the SeHCAT percentage retention-this effect may be related primarily to a decreased bile acid ileal absorption.

Airway structural cells regulate TLR5-mediated mucosal adjuvant activity.

PubMed

Van Maele, L; Fougeron, D; Janot, L; Didierlaurent, A; Cayet, D; Tabareau, J; Rumbo, M; Corvo-Chamaillard, S; Boulenouar, S; Jeffs, S; Vande Walle, L; Lamkanfi, M; Lemoine, Y; Erard, F; Hot, D; Hussell, T; Ryffel, B; Benecke, A G; Sirard, J-C

2014-05-01

Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin's mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines.

Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

USDA-ARS?s Scientific Manuscript database

Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are ri...

Determination of additivity of apparent and standardized ileal digestibility of amino acids in diets containing multiple protein sources fed to growing pigs.

PubMed

Xue, P C; Ragland, D; Adeola, O

2014-09-01

An experiment was conducted in growing pigs to investigate the additivity of apparent ileal digestibility (AID) or standardized ileal digestibility (SID) of CP and AA in mixed diets containing multiple protein sources. Using the determined AID or SID for CP and AA in corn, soybean meal (SBM), corn distillers' dried grains with solubles (DDGS), or canola meal (CM), the AID or SID for 4 mixed diets based on corn-SBM, corn-SBM-DDGS, corn-SBM-CM, or corn-SBM-DDGS-CM were predicted and compared with determined AID or SID, respectively. Eighteen growing pigs (initial BW = 61.3 ± 5.5 kg) were surgically fitted with T-cannulas and assigned to a duplicated 9 × 4 incomplete Latin square design with 9 diets and 4 periods. The 9 experimental diets consisted of a nitrogen-free diet (NFD) to estimate basal ileal endogenous loss (BEL) of AA, 4 semipurified diets to determine the AID and SID of CP and AA in the 4 ingredients, and 4 mixed diets to test the additivity of AID and SID. Chromic oxide was added as an indigestible marker. Pigs were fed 1 of the 9 diets during each 7-d period, and ileal digesta were collected on d 6 and 7, from 0800 to 1800 h. The analyzed AA levels for the mixed diets were close to the calculated values based on the AA composition of each ingredient. The results revealed that the predicted SID were consistent with determined values, except for Leu, Thr, Asp, Cys, Pro, and Ser in the corn-SBM diet and Met and Cys in the corn-SBM-DDGS diet. The determined AID for total AA and Arg, His, Trp, Gly, and Pro in the corn-SBM diet were greater (P < 0.05) than predicted. For the corn-SBM-DDGS diet, the determined AID were greater (P < 0.05) than predicted AID for CP, total AA, and all AA except for Arg, Leu, and Pro. In the corn-SBM-CM diet, the determined AID were greater (P < 0.05) than predicted AID for Arg, Cys, and Gly. When compared with determined values, predicted AID in the corn-SBM-DDGS-CM diet were lower (P < 0.05) for total AA and Arg, Met, Cys, and

Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome.

PubMed

Basu, Sayan; Pillai, Vinay Sukumara; Sangwan, Virender S

2013-11-01

To describe clinical outcomes of complications afflicting the autologous oral mucous membrane graft after modified osteo-odonto keratoprosthesis surgery in chronic Stevens-Johnson syndrome (SJS). Prospective case series. This study included 30 eyes of 30 patients with SJS-induced dry keratinized ocular surfaces; the patients underwent various stages of this procedure between August 2009 and February 2012. Mucosal complications were classified as either necrosis or overgrowth. Mucosal necrosis was managed according to a predesigned algorithm based on timing (pre- and postimplantation) and location (central or peripheral) of necrosis. Cases with mucosal overgrowth underwent mucosal debulking and trimming. Mucosal necrosis developed in 15 (50%) eyes and overgrowth in 4 (13.3%) eyes. Preimplantation necrosis (n = 7) was initially managed conservatively, but 2 eyes required free labial-mucous membrane grafting for persistent corneal exposure. Free labial-mucous membrane grafting was performed in all cases of postimplantation necrosis (n = 10), but 8 eyes required additional tarsal pedicle flaps (n = 6, for peripheral necrosis) or through-the-lid revisions (n = 2, for central necrosis). Debulking and trimming effectively managed all cases of mucosal overgrowth, but 3 eyes required repeat procedures. At 24.1 ± 6.5 months postimplantation, the keratoprosthesis was retained in all eyes, and the probability of maintaining 20/60 or better vision was similar in eyes with or without mucosal necrosis (86 ± 8.8% vs 80 ± 10.3%). Mucosal complications, especially necrosis, occurred commonly following modified osteo-odonto keratoprosthesis surgery in dry keratinized post-SJS eyes. The algorithm-based management approach described in this study was successful in treating these complications, retaining the prosthesis and preserving useful vision. Copyright © 2013 Elsevier Inc. All rights reserved.

[Therapeutic effect of rebamipide for oral mucositis associated with FEC therapy for breast cancer].

PubMed

Enami, Akiko; Masuda, Norikazu; Yamamura, Jun; Mizutani, Makiko; Yasojima, Hiroyuki; Shikata, Ayako; Masaoka, Miyuki; Takada, Seiko; Bamba, Nao; Yamamoto, Mie; Abe, Megumi; Makihara, Katsuya

2014-11-01

No guidelines for supportive drug therapy have been established for oral mucositis occurring during cancer chemotherapy. We retrospectively examined the progression of oral mucositis in 91 patients with breast cancer who received the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 regimen between September 2007 and August 2008. Daily rebamipide was administered to patients with oral mucositis as per hospital protocol to evaluate the hypothesized preventive and mucosal protective effects of rebamipide(Mucosta®). Oral mucositis was observed in 43 patients (47%)during 4 courses of FEC. The median age of the patients was 55 years(range, 32-76 years). Of the 91 patients, 49 patients who did not receive rebamipide during the 4 FEC courses were classified as group A, 14 patients who received rebamipide before the start of FEC were classified as group B, and 28 patients who received rebamipide after developing oral mucositis were classified as group C. The incidence of oral mucositis at the start of FEC with or without rebamipide administration was observed in 5 patients in group B (36%) and 38 patients in groups A and C (49%) (p=0.3472). The mucositis grade was G1 in 4 patients and G2 in 1 patient in group B, and G1 in 20 patients and G2 plus G3 in 18 patients in groups A and C (p=0.2467). In group C, the grade decreased in 25 patients (89%) and did not occur (G0) in 17 patients (61%) during the next course, and 15 patients (54%) continued to the final course without any occurrence of mucositis. These results suggest that rebamipide is effective for the treatment of oral mucositis. Although significant differences were not observed in the groups, rebamipide has the potential to prevent development of oral mucositis and alleviate its symptoms, and seems promising as a new supportive drug therapy. We hope to verify the preventive and protective effects of rebamipide by conducting a prospective, randomized trial while treating oral mucositis with basic oral care

Management of ileal perforation due to typhoid fever.

PubMed Central

Kim, J P; Oh, S K; Jarrett, F

1975-01-01

The results of the surgical management of 161 cases of ileal perforation due to typhoid fever are presented. Most were seen after an illness of 2-4 weeks, and because of delays in seeking hospital admission, more than half were explored more than 24 hours after their perforation occurred. All patients were prepared for operation with nasogastric suction, intravenous fluids, and antibiotics. At laparotomy, 80% had considerable quantities of pus and small bowel contents in the peritoneal cavity and the remainder had localized abscesses; there were no instances of localization of the perforation. One hundred three of these patients underwent simple closure of their perforations, while 43 underwent small bowel resection, usually because of multiple perforations. Exteriorization or drainage were performed only in patients too sick to tolerate a more appropriate procedure. The overall mortality was 9.9%. The authors believe that typhoid perforations can best be dealt with at operation. Delay in operative intervention adversely affects the survival rate after surgery. Chloramphenicol is used as the drug of choice. PMID:1119873

Low-protein diets affect ileal amino acid digestibility and gene expression of digestive enzymes in growing and finishing pigs.

PubMed

He, Liuqin; Wu, Li; Xu, Zhiqi; Li, Tiejun; Yao, Kang; Cui, Zhijie; Yin, Yulong; Wu, Guoyao

2016-01-01

The objective of this study was to evaluate effects of dietary crude protein (CP) intake on ileal amino acid digestibilities and expression of genes for digestive enzymes in growing and finishing pigs. In Experiment 1, 18 growing pigs (average initial BW = 36.5 kg) were assigned randomly into one of three treatments (n = 6/treatment group) representing normal (18 % CP), low (15 % CP), and very low (12 % CP) protein intake. In Experiment 2, 18 finishing pigs (average initial BW = 62.3 kg) were allotted randomly into one of three treatments (n = 6/treatment group), representing normal (16 % CP), low (13 % CP) and very low (10 % CP) protein intake. In both experiments, diets with low and very low CP were supplemented with crystalline amino acids to achieve equal content of standardized ileal digestible Lys, Met, Thr, and Trp, and were provided to pigs ad libitum. Daily feed intake, BW, and feed/gain ratios were determined. At the end of each experiment, all pigs were slaughtered to collect pancreas, small-intestine samples, and terminal ileal chymes. Samples were used for determining expression of genes for digestive enzymes and ileal amino acid digestibilities. Growing pigs fed the 12 % CP and 15 % CP diets had lower final body weight (P < 0.01) and ADG (P < 0.0001) when compared with pigs fed the 18 % dietary CP diet. Growing pigs fed with the 12 % CP diet showed higher digestibilities for CP (P < 0.05), DM (P < 0.05), Lys (P < 0.0001), Met (P < 0.01), Cys (P < 0.01), Thr (P < 0.01), Trp (P < 0.05), Val (P < 0.05), Phe (P < 0.05), Ala (P < 0.05), Cys (P < 0.01), and Gly (P < 0.05) than those fed the 18 % CP diet. Finishing pigs fed the 16 % CP diet had a higher (P < 0.01) final body weight than those fed the 10 % CP diet. mRNA levels for digestive enzymes (trypsinogen, chymotrypsin B, and dipeptidases-II and III) differed among the three groups of pigs (P < 0.05), and no difference was noted in the genes expression between control group and lower CP group. These

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

PubMed Central

Timme-Laragy, Alicia R.; Goldstone, Jared V.; Imhoff, Barry R.; Stegeman, John J.; Hahn, Mark E.; Hansen, Jason M.

2013-01-01

Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous non-protein antioxidant defense molecule is the tri-peptide glutathione (γ-glutamyl-cysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0–5 days post-fertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and oxidized glutathione (GSH, GSSG) using HPLC, and calculated the whole embryo total glutathione (GSHT) concentrations and redox potentials (Eh) over 0–120 hours of zebrafish development (including mature oocytes, fertilization, mid-blastula transition, gastrulation, somitogenesis, pharyngula, pre-hatch embryos, and hatched eleutheroembryos). GSHT concentration doubled between 12 hours post fertilization (hpf) and hatching. The GSH Eh increased, becoming more oxidizing during the first 12 h, and then oscillated around −190 mV through organogenesis, followed by a rapid change, associated with hatching, to a more negative (more reducing) Eh (−220 mV). After hatching, Eh stabilized and remained steady through 120 hpf. The dynamic changes in GSH redox status and concentration defined discrete windows of development: primary organogenesis, organ differentiation, and larval growth. We identified the set of zebrafish genes involved in the synthesis, utilization, and recycling of GSH, including several novel paralogs, and measured how expression of these genes changes during development. Ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox state is tightly regulated early in development. This study

Feedback inhibition by thiols outranks glutathione depletion: a luciferase-based screen reveals glutathione-deficient γ-ECS and glutathione synthetase mutants impaired in cadmium-induced sulfate assimilation.

PubMed

Jobe, Timothy O; Sung, Dong-Yul; Akmakjian, Garo; Pham, Allis; Komives, Elizabeth A; Mendoza-Cózatl, David G; Schroeder, Julian I

2012-06-01

Plants exposed to heavy metals rapidly induce changes in gene expression that activate and enhance detoxification mechanisms, including toxic-metal chelation and the scavenging of reactive oxygen species. However, the mechanisms mediating toxic heavy metal-induced gene expression remain largely unknown. To genetically elucidate cadmium-specific transcriptional responses in Arabidopsis, we designed a genetic screen based on the activation of a cadmium-inducible reporter gene. Microarray studies identified a high-affinity sulfate transporter (SULTR1;2) among the most robust and rapid cadmium-inducible transcripts. The SULTR1;2 promoter (2.2 kb) was fused with the firefly luciferase reporter gene to quantitatively report the transcriptional response of plants exposed to cadmium. Stably transformed luciferase reporter lines were ethyl methanesulfonate (EMS) mutagenized, and stable M(2) seedlings were screened for an abnormal luciferase response during exposure to cadmium. The screen identified non-allelic mutant lines that fell into one of three categories: (i) super response to cadmium (SRC) mutants; (ii) constitutive response to cadmium (CRC) mutants; or (iii) non-response and reduced response to cadmium (NRC) mutants. Two nrc mutants, nrc1 and nrc2, were mapped, cloned and further characterized. The nrc1 mutation was mapped to the γ-glutamylcysteine synthetase gene and the nrc2 mutation was identified as the first viable recessive mutant allele in the glutathione synthetase gene. Moreover, genetic, HPLC mass spectrometry, and gene expression analysis of the nrc1 and nrc2 mutants, revealed that intracellular glutathione depletion alone would be insufficient to induce gene expression of sulfate uptake and assimilation mechanisms. Our results modify the glutathione-depletion driven model for sulfate assimilation gene induction during cadmium stress, and suggest that an enhanced oxidative state and depletion of upstream thiols, in addition to glutathione depletion

A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

PubMed

Li, Ling; Zhang, Guo-Fang; Lee, Kwangwon; Lopez, Rocio; Previs, Stephen F; Willard, Belinda; McCullough, Arthur; Kasumov, Takhar

2016-07-01

Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the (2)H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P<0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P<0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the (2)H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotrim, Ana P.; Yoshikawa, Masanobu; Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa

Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size andmore » tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.« less

Surgical treatment of ulcerative colitis: Ileorectal vs ileal pouch-anal anastomosis

PubMed Central

Scoglio, Daniele; Ahmed Ali, Usama; Fichera, Alessandro

2014-01-01

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current gold standard in the surgical treatment of ulcerative colitis (UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk. PMID:25309058

Potential of SeHCAT retention as an indicator of terminal ileal involvement in inflammatory bowel disease.

PubMed

Holdstock, G; Phillips, G; Hames, T K; Condon, B R; Fleming, J S; Smith, C L; Ackery, D M

1985-01-01

The absorption of 75Se-23-selena-25-homotaurocholate (SeHCAT) was compared with vitamin-B12 absorption and conventional radiography in 44 patients with inflammatory bowel disease. The retention of SeHCAT was normal in 11 patients with ulcerative colitis but was abnormally low in 9 patients with terminal-ileal resection, 9 out of 14 patients with small-bowel Crohn's disease and in 2 out of 10 patients with Crohn's colitis. The 5 patients with small-bowel Crohn's disease and normal retention had either inactive disease or no radiological evidence of terminal ileal involvement. Measurements of the absorption of vitamin B12 did not discriminate between these groups, and there was very poor correlation between B12 and SeHCAT absorption (r = 0.506, P less than 0.05). There was extremely good correlation of SeHCAT retention measured using a wholebody counter with that measured using an uncollimated gamma camera (r = 0.96, P less than 0.001). The results suggest that SeHCAT retention may prove complementary to conventional methods of assessing small-bowel disease in patients with inflammatory bowel disease. As measurement by gamma camera is feasible, this test can be used in most departments of nuclear medicine.

Experimental evaluation of ileal patch in delayed primary repair of penetrating colon injuries: An animal study.

PubMed

Abbasi, Hamid Reza; Bolandparvaz, Shahram; Yarmohammadi, Hooman; Geramizadeh, Bita; Tanideh, Nader; Paydar, Shahram; Hosseini, Seyed Vahid

2006-10-01

Primary repair of traumatic colonic perforation is progressively gaining acceptance as the best method of management. However, when delayed, the risk of infection-related complications may increase. Here, we present a new method of repairing colon perforation in the presence of peritonitis. Acute colon injury was simulated in 22 German shepherd dogs. The dogs were randomly divided into two groups of 11 and after 24 hours they were operated on. The perforations were repaired by subserosal suture technique. In the first group (group A), ileal patch was used. In the other group (group B), the colon was closed by debridement and anastomosis. After 6 weeks, the repairs were assessed on the basis of survival, gross and histological assessments. Nine (82%) dogs in group A and six (56%) in group B survived. Ileal patch utilization significantly decreased the mortality rate (p < 0.05). The cause of death in two group A dogs and five group B dogs was peritonitis and intra-abdominal abscess formation. None of the surviving dogs showed evidence of anastomotic leakage or breakdown. Small bowel patch used in primary repair of colon injury in the presence of peritonitis may decrease the risk of postoperative infection-related complications and the mortality rate.

Novel prototype sewing device, EndoSew®, for minimally invasive surgery: an extracorporeal ileal conduit construction pilot study in 10 patients.

PubMed

Roth, Beat; Birkhäuser, Frédéric D; Thalmann, George N; Zehnder, Pascal

2013-11-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The EndoSew(®) prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and reliable, its greatest advantage being a 2.4-fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew(®) suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications. We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device EndoSew(®). The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions. To evaluate the feasibility and safety of the novel prototype sewing device EndoSew(®) in placing an extracorporeal resorbable running suture for ileal conduits. We conducted a prospective single-centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an EndoSew(®) running suture. The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew(®) only. Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14. Secondary endpoints were the time requirements and complications ≤30 days after surgery. A complete EndoSew(®) running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure. In three

Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione*

PubMed Central

Seefeldt, Teresa; Zhao, Yong; Chen, Wei; Raza, Ashraf S.; Carlson, Laura; Herman, Jocqueline; Stoebner, Adam; Hanson, Sarah; Foll, Ryan; Guan, Xiangming

2009-01-01

Thiol redox state (TRS) is an important parameter to reflect intracellular oxidative stress and is associated with various normal and abnormal biochemical processes. Agents that can be used to increase intracellular TRS will be valuable tools in TRS-related research. Glutathione reductase (GR) is a critical enzyme in the homeostasis of TRS. The enzyme catalyzes the reduction of GSSG to GSH to maintain a high GSH:GSSG ratio. Inhibition of the enzyme can be used to increase TRS. Despite the reports of various GR inhibitors, N,N-bis(2-chloroethyl)-N-nitrosourea, an anticancer drug with IC50 = 647 μm against yeast GR, remains the most commonly used GR inhibitor in the literature. However, the toxicity caused by nonspecific interactions, as well as inhibition of DNA synthesis, complicates the use of N,N-bis(2-chloroethyl)-N-nitrosourea as a GR inhibitor. We report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a novel irreversible GR inhibitor. 2-AAPA was prepared by one-step synthesis from commercially available reagents. The Ki and kinact of 2-AAPA against yeast GR were determined to be 56 μm and 0.1 min–1, respectively. At the concentration that produced >80% yeast GR inhibition, 2-AAPA showed no inhibition against glutamylcysteine synthetase, glutathione synthetase, catalase, and superoxide dismutase, but minimal inhibition against glutathione S-transferase and glutathione peroxidase. In CV-1 cells, 2-AAPA (0.1 mm) produced 97% GR inhibition, 25% GSH reduction, and a 5-fold increase in GSSG in 20 min. The compound can be a useful tool in TRS-related research. PMID:19049979

High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface.

PubMed

Angeli, T R; Du, P; Paskaranandavadivel, N; Sathar, S; Hall, A; Asirvatham, S J; Farrugia, G; Windsor, J A; Cheng, L K; O'Grady, G

2017-05-01

Gastric motility is coordinated by bioelectrical slow waves, and gastric dysrhythmias are reported in motility disorders. High-resolution (HR) mapping has advanced the accurate assessment of gastric dysrhythmias, offering promise as a diagnostic technique. However, HR mapping has been restricted to invasive surgical serosal access. This study investigates the feasibility of HR mapping from the gastric mucosal surface. Experiments were conducted in vivo in 14 weaner pigs. Reference serosal recordings were performed with flexible-printed-circuit (FPC) arrays (128-192 electrodes). Mucosal recordings were performed by two methods: (i) FPC array aligned directly opposite the serosal array, and (ii) cardiac mapping catheter modified for gastric mucosal recordings. Slow-wave propagation and morphology characteristics were quantified and compared between simultaneous serosal and mucosal recordings. Slow-wave activity was consistently recorded from the mucosal surface from both electrode arrays. Mucosally recorded slow-wave propagation was consistent with reference serosal activation pattern, frequency (P≥.3), and velocity (P≥.4). However, mucosally recorded slow-wave morphology exhibited reduced amplitude (65-72% reduced, P<.001) and wider downstroke width (18-31% wider, P≤.02), compared to serosal data. Dysrhythmias were successfully mapped and classified from the mucosal surface, accorded with serosal data, and were consistent with known dysrhythmic mechanisms in the porcine model. High-resolution gastric electrical mapping was achieved from the mucosal surface, and demonstrated consistent propagation characteristics with serosal data. However, mucosal signal morphology was attenuated, demonstrating necessity for optimized electrode designs and analytical algorithms. This study demonstrates feasibility of endoscopic HR mapping, providing a foundation for advancement of minimally invasive spatiotemporal gastric mapping as a clinical and scientific tool. © 2016 John

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

PubMed

Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

2007-10-01

Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

The mucosal immune system of fish: the evolution of tolerating commensals while fighting pathogens

PubMed Central

Gomez, Daniela; Sunyer, J Oriol; Salinas, Irene

2013-01-01

The field of mucosal immunology research has grown fast over the past few years, and our understanding on how mucosal surfaces respond to complex antigenic cocktails is expanding tremendously. With the advent of new molecular sequencing techniques, it is easier to understand how the immune system of vertebrates is, to a great extent, orchestrated by the complex microbial communities that live in symbiosis with their hosts. The commensal microbiota is now seen as the “extended self” by many scientists. Similarly, fish immunologist are devoting important research efforts to the field of mucosal immunity and commensals. Recent breakthroughs on our understanding of mucosal immune responses in teleost fish open up the potential of teleosts as animal research models for the study of human mucosal diseases. Additionally, this new knowledge places immunologists in a better position to specifically target the fish mucosal immune system while rationally designing mucosal vaccines and other immunotherapies. In this review, an updated view on how teleost skin, gills and gut immune cells and molecules, function in response to pathogens and commensals is provided. Finally, some of the future avenues that the field of fish mucosal immunity may follow in the next years are highlighted. PMID:24099804

Effect of topical honey on limitation of radiation-induced oral mucositis: an intervention study.

PubMed

Khanal, B; Baliga, M; Uppal, N

2010-12-01

Radiation therapy for oral carcinoma is therapeutically useful in dose of at least 6000 cGy but causes mucositis that severely interferes with oral function. The literature indicates that honey appears to promote wound healing, so the authors investigated whether its anti-inflammatory properties might limit the severity of radiation-induced oral mucositis. A single-blinded, randomized, controlled clinical trial was carried out to compare the mucositis-limiting qualities of honey with lignocaine. A visual assessment scale permitted scoring of degrees of mucositis and statistical evaluation of the results was performed using the χ(2) test. Only 1 of 20 patients in the honey group developed intolerable oral mucositis compared with the lignocaine group, indicating that honey is strongly protective (RR=0.067) against the development of mucositis. The proportion of patients with intolerable oral mucositis was lower in the honey group and this was statistically significant (p=0.000). Honey applied topically to the oral mucosa of patients undergoing radiation therapy appears to provide a distinct benefit by limiting the severity of mucositis. Honey is readily available, affordable and well accepted by patients making it useful for improving the quality of life in irradiated patients. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Different roles of glutathione in copper and zinc chelation in Brassica napus roots.

PubMed

Zlobin, Ilya E; Kartashov, Alexander V; Shpakovski, George V

2017-09-01

We investigated the specific features of copper and zinc excess action on the roots of canola (Brassica napus L.) plants. Copper rapidly accumulated in canola root cells and reached saturation during several hours of treatment, whereas the root zinc content increased relatively slowly. Excessive copper and zinc entry inside the cell resulted in significant cell damage, as evidenced by alterations in plasmalemma permeability and decreases in cellular enzymatic activity. Zinc excess specifically damaged root hair cells, which correlated with a pronounced elevation of their labile zinc level. In vitro, we showed that reduced glutathione (GSH) readily reacted with copper ions to form complexes with blocked sulfhydryl groups. In contrast, zinc ions were ineffective as glutathione blockers, and glutathione molecules did not lose their specific chemical activity in the presence of Zn 2+ ions. The effect of copper and zinc excess on the glutathione pool in canola root cells was analysed by a combination of biochemical determination of total and oxidized glutathione contents and fluorescent staining of free reduced glutathione with monochlorobimane dye. Excess copper led to dose-dependent diminution of free reduced glutathione contents in the root cells, which could not be explained by the loss of total cellular glutathione or its oxidation. In contrast, we observed little effect of much higher intracellular zinc concentrations on the free reduced glutathione content. We concluded that GSH plays an important role in copper excess, but not zinc excess chelation, in canola root cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Long-term functional outcomes after radical cystectomy with ileal bladder substitute: does the definition of continence matter?

PubMed

Liedberg, Fredrik; Ahlgren, Göran; Baseckas, Gediminas; Gudjonsson, Sigurdur; Håkansson, Ulf; Lindquist, Sara; Löfgren, Annica; Patschan, Oliver; Siller, Carina; Sjödahl, Gottfrid

2017-02-01

Functional outcomes after ileal bladder substitution reflect the expectations of future patients at a particular centre. The aim of this study was to use validated questionnaires and a pad-weighing test to investigate functional outcomes after neobladder reconstruction at long-term follow-up in patients at a single centre. During 2005 - 2015, 75 patients received a Studer ileal bladder substitute at the Department of Urology, Malmö. Forty-six of these patients were alive for follow-up and were evaluated using the pad-weighing test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Five of 37 evaluable patients (14%) were considered fully continent, reporting a pad-weighing test result of 0 g and an ICIQ-UI-SF score of 0. The median ICIQ-UI-SF score was 8 [interquartile range (IQR) 3-11], and seven patients (17%) were continent according to the ICIQ-UI-SF score only. In the pad-weighing test, 28 out of 37 patients (76%) reported 0 g day-time leakage whereas only 12 out of 37 patients (32%) reported 0 g night-time leakage. At follow-up, nine out of 39 (23%) of evaluable male patients were potent. The median ICIQ-UI-SF score was significantly lower during the second half of the study period [4 (IQR 0-8) vs 10 (IQR 6-14); p = .003]. The inverse applied to the median IIEF score [5 (IQR 3-12) vs 2 (IQR 1-4); p = .02]. Functional outcomes at long-term follow-up after radical cystectomy and Studer ileal bladder substitute were at best modest in this series. Better outcomes during the second half of the study period might be explained by improved patient selection and a refined surgical technique, but possibly also by longer follow-up of patients during the first half of the period resulting in a more pronounced time-dependent decline in functional outcomes.

Relationship between in vitro assays and standardized ileal amino acid digestibility of animal protein meals in broilers.

PubMed

Rochell, S J; Kuhlers, D L; Dozier, W A

2013-01-01

Two identical trials were conducted to determine the relationship of a novel digestive enzyme assay, Poultry Complete IDEA (PC IDEA), and the pepsin digestibility assay with standardized ileal amino acid digestibility (SIAAD) of 20 animal protein meals (APM) fed to broilers from 25 to 30 d of age. Animal protein meals included 10 meat and bone meals (MBM) consisting of bovine, porcine, or mixed bovine and porcine raw materials (BP), and 10 animal protein blends containing animal proteins from various species. Treatments consisted of 20 semi-purified diets containing 1 APM as the sole source of dietary amino acids (AA), and 1 N-free diet to determine endogenous ileal AA flow. With the exception of the N-free diet, diets were formulated to contain 20% CP. In each trial, 756 Ross × Ross 708 male broilers were housed in battery cages and randomly assigned to 21 dietary treatments on d 25 (12 birds per cage; 3 replicate cages), and ileal digesta were collected on d 30 for determination of SIAAD. Pepsin digestibility and PC IDEA were determined for APM samples from each experimental diet (3 replicates per trial; 6 total replicates). Pepsin digestibility and PC IDEA were both correlated (P < 0.001) with SIAAD for each AA. Multiple linear regression of PC IDEA and pepsin digestibility on SIAAD resulted in the following equations: % Lys SIAAD = [-9.65 + (0.38 × % PC IDEA predicted Lys digestibility) + (0.69 × % pepsin digestibility)], % Met SIAAD = [-35.95 + (0.62 × % PC IDEA predicted Met digestibility) + (0.75 × % pepsin digestibility)], % Thr SIAAD = [-77.5 + (0.39 × % PC IDEA predicted Thr digestibility) + (1.37 × % pepsin digestibility)]. Values of R(2) were 0.46, 0.47, and 0.55 for Lys, Met, and Thr, respectively. The relatively low R(2) values may have been due to the limited range in SIAAD observed for the 20 APM, and additional data on APM varying in SIAAD are needed.

Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip.

PubMed

Ponsero, Alise J; Igbaria, Aeid; Darch, Maxwell A; Miled, Samia; Outten, Caryn E; Winther, Jakob R; Palais, Gael; D'Autréaux, Benoit; Delaunay-Moisan, Agnès; Toledano, Michel B

2017-09-21

In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H 2 O 2 -dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient. Copyright © 2017 Elsevier Inc. All rights reserved.

JAM related proteins in mucosal homeostasis and inflammation

PubMed Central

Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A.

2014-01-01

Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include Junctional Adhesion Molecules (JAMs) that belong to the CTX (Cortical Thymocyte marker for Xenopus) family of proteins. JAM family encompasses three classical members (JAM-A, -B and –C) and related molecules including JAM4, JAM-Like protein (JAM-L), Coxsackie and Adenovirus Receptor (CAR), CAR-Like Membrane Protein (CLMP) and Endothelial cell-Selective Adhesion Molecule (ESAM). JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation. PMID:24667924

Systemic and Mucosal Differences in HIV Burden, Immune and Therapeutic Responses

PubMed Central

Wahl, Sharon M.; Redford, Maryann; Christensen, Shawna; Mack, Wendy; Cohn, Jon; Janoff, Edward N.; Mestecky, Jiri; Jenson, Hal B.; Navazesh, Mahvash; Cohen, Mardge; Reichelderfer, Patricia; Kovacs, Andrea

2011-01-01

Background Mucosal tissues represent major targets for HIV transmission, but differ in susceptibility and reservoir function by unknown mechanisms. Methods In a cross-sectional study, HIV RNA and infectious virus were compared between oral and genital compartments and blood in HIV-infected women, in association with clinical parameters, co-pathogens and putative innate and adaptive HIV inhibitors. Results HIV RNA was detectable in 24.5% of women from all 3 compartments, whereas 45% had RNA in only one or two sites. By comparison, infectious HIV, present in blood of the majority, was rare in mucosal sites. Innate mediators, SLPI and TSP, were highest in mucosae. Highly active antiretroviral therapy (HAART) was associated with an 80% decreased probability of shedding. Multivariate logistic regression models revealed that mucosal HIV RNA was associated with higher plasma RNA, infectious virus, and total mucosal IgA, but not IgG. There was a 37-fold increased probability of detecting RNA in both genital and oral specimens (P=0.008;P=0.02, respectively) among women in highest vs lowest IgA tertiles. Conclusions Mucosal sites exhibit distinct characteristics of infectious HIV, viral shedding and responses to therapy, dependent upon both systemic and local factors. Of the putative innate and adaptive mucosal defense factors examined, only IgA was associated with HIV RNA shedding. However, rather than being protective, there was a striking increase in probability of detectable HIV RNA shedding in women with highest total IgA. PMID:21239996

Management of a large mucosal defect after duodenal endoscopic resection

PubMed Central

Fujihara, Shintaro; Mori, Hirohito; Kobara, Hideki; Nishiyama, Noriko; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Masaki, Tsutomu

2016-01-01

Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment. PMID:27547003

Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

PubMed

Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

2015-06-01

Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. © 2015 by the Society for Experimental Biology and Medicine.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Rectal mucosal electrosensitivity - what is being tested?

PubMed

Meagher, A P; Kennedy, M L; Lubowski, D Z

1996-01-01

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by

Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy.

PubMed

Rae, Caroline D; Williams, Stephen R

2017-07-15

We review the transport, synthesis and catabolism of glutathione in the brain as well as its compartmentation and biochemistry in different brain cells. The major reactions involving glutathione are reviewed and the factors limiting its availability in brain cells are discussed. We also describe and critique current methods for measuring glutathione in the human brain using magnetic resonance spectroscopy, and review the literature on glutathione measurements in healthy brains and in neurological, psychiatric, neurodegenerative and neurodevelopmental conditions In summary: Healthy human brain glutathione concentration is ∼1-2 mM, but it varies by brain region, with evidence of gender differences and age effects; in neurological disease glutathione appears reduced in multiple sclerosis, motor neurone disease and epilepsy, while being increased in meningiomas; in psychiatric disease the picture is complex and confounded by methodological differences, regional effects, length of disease and drug-treatment. Both increases and decreases in glutathione have been reported in depression and schizophrenia. In Alzheimer's disease and mild cognitive impairment there is evidence for a decrease in glutathione compared to age-matched healthy controls. Improved methods to measure glutathione in vivo will provide better precision in glutathione determination and help resolve the complex biochemistry of this molecule in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Glutathione on the Taste and Texture of Type I Sourdough Bread.

PubMed

Tang, Kai Xing; Zhao, Cindy J; Gänzle, Michael G

2017-05-31

Type I sourdough fermentations with Lactobacillus sanfranciscensis as predominant organism accumulate reduced glutathione through glutathione reductase (GshR) activity of L. sanfranciscensis. Reduced glutathione acts as chain terminator for gluten polymerization but is also kokumi-active and may thus enhance bread taste. This study implemented a type I model sourdough fermentations to quantitate glutathione accumulation sourdough, bread dough, and bread and to assess the effect of L. sanfranciscensis GshR on bread volume by comparison of L. sanfranciscensis and an isogenic strain devoid of GshR. L. sanfranciscensis sourdough accumulated the highest amount of reduced glutathione during proofing. Bread produced with the wild type strain had a lower volume when compared to the gshR deficient mutant. The accumulation of γ-glutamyl-cysteine was also higher in L. sanfranciscensis sourdoughs when compared to doughs fermented with the gshR mutant strain. The accumulation of reduced glutathione in L. sanfranciscensis bread did not enhance the saltiness of bread.

Identification of risk factors for mucosal injury during laparoscopic Heller myotomy for achalasia.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shusuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-02-01

Mucosal injury during myotomy is the most frequent complication seen with the Heller-Dor procedure for achalasia. The present study aimed to examine risk factors for such mucosal injury during this procedure. This was a retrospective analysis of patients who underwent the laparoscopic Heller-Dor procedure for achalasia at a single facility. Variables for evaluation included patient characteristics, preoperative pathophysiological findings, and surgeon's operative experience. Logistic regression was used to identify risk factors. We also examined surgical outcomes and the degree of patient satisfaction in relation to intraoperative mucosal injury. Four hundred thirty-five patients satisfied study criteria. Intraoperative mucosal injury occurred in 67 patients (15.4%). In univariate analysis, mucosal injury was significantly associated with the patient age ≥60 years, disease history ≥10 years, prior history of cardiac diseases, preoperative esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. In multivariate analysis involving these factors, the following variables were identified as risk factors: age ≥60 years, esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. The mucosal injury group had significant extension of the operative time and increased blood loss. However, there were no significant differences between the two groups in the incidence of reflux esophagitis or the degree of symptom alleviation postoperatively. The fragile esophagus caused by advanced patient age and/or dilatation were risk factor for mucosal injury during laparoscopic Heller-Dor procedure. And novice surgeon was also identified as an isolated risk factor for mucosal injury.

Dermoscopic appearance of an amelanotic mucosal melanoma

PubMed Central

Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

2016-01-01

Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei.

PubMed

Pettersson, Eva U; Ljunggren, Erland L; Morrison, David A; Mattsson, Jens G

2005-01-01

The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. Our interest in S. scabiei led us to further characterise a glutathione S-transferase. This multifunctional enzyme is a target for vaccine and drug development in several parasitic diseases. The S. scabiei glutathione S-transferase open reading frame reported here is 684 nucleotides long and yields a protein with a predicted molecular mass of 26 kDa. Through phylogenetic analysis the enzyme was classified as a delta-class glutathione S-transferase, and our paper is the first to report that delta-class glutathione S-transferases occur in organisms other than insects. The recombinant S. scabiei glutathione S-transferase was expressed in Escherichia coli via three different constructs and purified for biochemical analysis. The S. scabiei glutathione S-transferase was active towards the substrate 1-chloro-2,4-dinitrobenzene, though the positioning of fusion partners influenced the kinetic activity of the enzyme. Polyclonal antibodies raised against S. scabiei glutathione S-transferase specifically localised the enzyme to the integument of the epidermis and cavities surrounding internal organs in adult parasites. However, some minor staining of parasite intestines was observed. No staining was seen in host tissues, nor could we detect any antibody response against S. scabiei glutathione S-transferase in sera from naturally S. scabiei infected dogs or pigs. Additionally, the polyclonal sera raised against recombinant S. scabiei glutathione S-transferase readily detected a protein from mites, corresponding to the predicted size of native glutathione S-transferase.

Eosinophils in mucosal immune responses

PubMed Central

Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

1-3-A Resolution Structure of Human Glutathione S-Transferase With S-Hexyl Glutathione Bound Reveals Possible Extended Ligandin Binding Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trong, I.Le; Stenkamp, R.E.; Ibarra, C.

2005-08-22

Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathionemore » binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.« less

Glutathione Preservation during Storage of Rat Lenses in Optisol-GS and Castor Oil

PubMed Central

Holm, Thomas; Brøgger-Jensen, Martin Rocho; Johnson, Leif; Kessel, Line

2013-01-01

Background Glutathione concentration in the lens decreases in aging and cataractous lenses, providing a marker for tissue condition. Experimental procedures requiring unfrozen lenses from donor banks rely on transportation in storage medium, affecting lens homeostasis and alterations in glutathione levels. The aim of the study was to examine the effects of Optisol-GS and castor oil on lens condition, determined from their ability to maintain glutathione concentrations. Methodology/Principal Findings Rat lenses were stored in the two types of storage media at varying time intervals up to 3 days. Glutathione concentration was afterwards determined in an enzymatic detection assay, specific for both reduced and oxidized forms. Lenses removed immediately after death exhibited a glutathione concentration of 4.70±0.29 mM. In vitro stored lenses in Optisol-GS lost glutathione quickly, ending with a concentration of 0.60±0.34 mM after 3 days while castor oil stored lenses exhibited a slower decline and ended at 3 times the concentration. A group of lenses were additionally stored under post mortem conditions within the host for 6 hours before its removal. Total glutathione after 6 hours was similar to that of lenses removed immediately after death, but with altered GSH and GSSG concentrations. Subsequent storage of these lenses in media showed changes similar to those in the first series of experiments, albeit to a lesser degree. Conclusions/Significance It was determined that storage in Optisol-GS resulted in a higher loss of glutathione than lenses stored in castor oil. Storage for more than 12 hours reduced glutathione to half its original concentration, and was considered unusable after 24 hours. PMID:24260265

One-pot synthesis of glutathione by a two-enzyme cascade using a thermophilic ATP regeneration system.

PubMed

Zhang, Xing; Wu, Hui; Huang, Bing; Li, Zhimin; Ye, Qin

2017-01-10

In vitro cascade catalysis using enzyme-based system is becoming a promising biomanufacturing platform for biofuels and biochemicals production. Glutathione is a pivotal non-protein thiol compound and widely applied in food and pharmaceutical industries. In this study, glutathione was synthesized by a bifunctional glutathione synthetase together with a thermophilic ATP regeneration system through a two-enzyme cascade in vitro. Four bifunctional glutathione synthetases from Streptococcus sanguinis, S. gordonii, S. uberis and Bacillus cereus were applied for glutathione synthesis. The bifunctional glutathione synthetase from S. sanguinis was selected and coupled with the polyphosphate kinase from Thermosynechococcus elongatus BP-1 for regenerating ATP to produce glutathione in one pot. In the optimized system, 28.5mM glutathione was produced within 5h due to efficient ATP regeneration from low-cost polyphosphate. The yield based on added l-cysteine reached 81.4% and the productivity of glutathione achieved 5.7mM/h. The one-pot system indicated a potential biotransformation platform for industrial production of glutathione. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of edaravone against radiation-induced oral mucositis in mice.

PubMed

Nakajima, Noriko; Watanabe, Shinichi; Kiyoi, Takeshi; Tanaka, Akihiro; Suemaru, Katsuya; Araki, Hiroaki

2015-03-01

Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(®)). Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy). To evaluate the protective effect of edaravone (30 and 300 mg/kg), administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra.

PubMed

Schröder, Katja; Bosch, Thomas C G

2016-11-01

Historically, mucosal immunity-i.e., the portion of the immune system that protects an organism's various mucous membranes from invasion by potentially pathogenic microbes-has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders. Copyright © 2016 Schröder and Bosch.

The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra

PubMed Central

Schröder, Katja

2016-01-01

ABSTRACT Historically, mucosal immunity—i.e., the portion of the immune system that protects an organism’s various mucous membranes from invasion by potentially pathogenic microbes—has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders. PMID:27803185

Endoscopic mucosal resection for early gastric cancer. A case report.

PubMed

Gheorghe, Cristian; Sporea, Ioan; Becheanu, Gabriel; Gheorghe, Liana

2002-03-01

European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure

Impact of PRRSV infection and dietary soybean meal on ileal amino acid digestibility and endogenous amino acid losses in growing pigs

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant disease in the swine industry and increasing soybean meal (SBM) during this disease challenge may improve performance. Our objectives were to determine the impact of SBM level on apparent total tract (ATTD) and ileal (AID) ...

Functional Aspects of Fish Mucosal Lectins-Interaction with Non-Self.

PubMed

Brinchmann, Monica Fengsrud; Patel, Deepti Manjari; Pinto, Nevil; Iversen, Martin Haugmo

2018-05-09

Mucosal surfaces are of key importance in protecting animals against external threats including pathogens. In the mucosal surfaces, host molecules interact with non-self to prevent infection and disease. Interestingly, both inhibition and stimulation of uptake hinder infection. In this review, the current knowledgebase on teleost mucosal lectins’ ability to interact with non-self is summarised with a focus on agglutination, growth inhibition, opsonisation, cell adhesion, and direct killing activities. Further research on lectins is essential, both to understand the immune system of fishes, since they rely more on the innate immune system than mammals, and also to explore these molecules’ antibiotic and antiparasitic activities against veterinary and human pathogens.

Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

PubMed

Patussi, Cleverson; Sassi, Laurindo Moacir; Munhoz, Eduardo Ciliao; Zanicotti, Roberta Targa Stramandinoli; Schussel, Juliana Lucena

2014-01-01

Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.

Lactobacillus acidophilus alleviates pouchitis after ileal pouch-anal anastomosis in rats.

PubMed

Xu, Yan-Yan; Zhang, Ying-Ying; He, An-Qi; Li, Kai-Yu; Gao, Sen-Yang; Liu, Gang

2017-07-14

To assess the therapeutic potential of Lactobacillus acidophilus (LA) for the treatment of pouchitis in a rat model. Sprague Dawley rats underwent proctocolectomy and ileal pouch-anal anastomosis followed by administration of dextran sulfate sodium (DSS) to induce pouchitis. Rats with pouchitis were randomly divided into three groups: no intervention (NI), normal saline (NS, 3 mL/d normal saline for 7 d), and LA (3 mL/d LA at 1× 10 10 colony-forming units for 7 d). General body condition was recorded and pouch specimens were obtained for histological examination. mRNA expression levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were determined by RT-PCR. Zonula occludens protein 1 (ZO-1) levels were measured by immunohistochemistry. LA reduced weight loss associated with pouchitis ( P < 0.05) and improved the symptoms of pouchitis in rats. Compared with the NI and NS groups, rats in the LA group showed earlier disappearance of hematochezia (6.17 ± 0.75, 6.50 ± 0.55, 3.17 ± 0.75, P < 0.05) and higher fecal scores (2.67 ± 0.48, 2.50 ± 0.51, 4.42 ± 0.50, respectively, P < 0.05). Histological scores were also lower in the LA group compared with the other two groups (7.17 ± 0.98, 8.00 ± 0.89, 4.00 ± 0.89, respectively, P < 0.05). mRNA expression levels of IL-1β, IL-6, and tumor necrosis factor-α were significantly reduced, while IL-10 mRNA levels were significantly increased in the LA group ( P < 0.05, respectively). ZO-1 protein levels were also significantly increased after administration of LA ( P < 0.05). LA alleviates pouchitis induced by DSS after ileal pouch-anal anastomosis by decreasing pro-inflammatory factors and increasing anti-inflammatory factors, and restoring ZO-1 expression in the mucosa.

Effect of T-2 Toxin, Fasting, and 2-Methyl-thiazolidine-4-carboxylate, a Glutathione Prodrug, on Hepatic Glutathione Levels1,2

DTIC Science & Technology

1986-11-14

Iftnvi fnr fard mirn: O Fo, M73 3 r0tiON OF I MOV 6s IS OBSOLETE SECURITY CLASSIFICATION OF THIS PACE (When Does Entoeed) , I I I I I 4.5± 0.39...Glende, 1973). An important cellular defense against peroxida- tive damage is the presence of glutathione and its use as an enzyme substrate or...cofactor. Even though intracellular glutathione concentration is in the millimolar range (Kosower and Kosower, 1978), there are conditions which lead to

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals

PubMed Central

Bailey, Ryan S.; Casey, Kevin P.; Pawar, Sachin S.; Garcia, Guilherme J. M.

2016-01-01

Importance Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. Objective To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. Design, Setting, and Participants Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Results The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔTexp-insp = 6.2 ± 2.6°C) than during resting breathing (ΔTexp-insp = 4.2 ± 2.3°C) in both locations (p < 10−13). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. Conclusions and Relevance The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation

Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration.

PubMed

Suga, Yasuyo; Takehana, Kenji

2017-09-01

S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b + TIM-4 + cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b + TIM-4 + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytochelatin synthesis and glutathione levels in response to heavy metals in tomato cells.

PubMed

Scheller, H V; Huang, B; Hatch, E; Goldsbrough, P B

1987-12-01

Cell suspension cultures of tomato, Lycopersicon esculentum Mill. cv VFNT-Cherry, produce phytochelatins (poly[gamma-glutamylcysteinyl]glycines) when exposed to cadmium. The synthesis of these peptides is accompanied by a decline in cellular levels of glutathione. Buthionine sulfoximine, an inhibitor of glutathione synthesis, inhibits the sustained production of phytochelatins. However, phytochelatin synthesis can occur in the presence of buthionine sulfoximine provided that sufficient glutathione is available. These results indicate that glutathione is a substrate for phytochelatin synthesis. The protein synthesis inhibitor cycloheximide does not affect the initial production of phytochelatin.

The glutathione defense system in the pathogenesis of rheumatoid arthritis.

PubMed

Hassan, M Q; Hadi, R A; Al-Rawi, Z S; Padron, V A; Stohs, S J

2001-01-01

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA. Copyright 2001 John Wiley & Sons, Ltd.

Reactivity of 9-aminoacridine drug quinacrine with glutathione limits its antiprion activity.

PubMed

Šafařík, Martin; Moško, Tibor; Zawada, Zbigniew; Šafaříková, Eva; Dračínský, Martin; Holada, Karel; Šebestík, Jaroslav

2017-06-01

Quinacrine-the drug based on 9-aminoacridine-failed in clinical trials for prion diseases, whereas it was active in in vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abundant glutathione. Here, we described the semi-large-scale synthesis of the acridinylated glutathione and the consequences of its formation on biological and biophysical activities. The acridinylated glutathione is one order of magnitude weaker prion protein binder than the parent quinacrine. Moreover, according to log D pH 7.4 , the glutathione conjugate is two orders of magnitude more hydrophilic than quinacrine. Its higher hydrophilicity and higher dsDNA binding potency will significantly decrease its bioavailability in membrane-like environment. The glutathione deactivates quinacrine not only directly but also decreases its bioavailability. Furthermore, the conjugate can spontaneously decompose to practically insoluble acridone, which is precipitated out from the living systems. © 2016 John Wiley & Sons A/S.

Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

PubMed

Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

2012-01-01

Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral

A Western diet induced NAFLD in LDLR−/− mice is associated with reduced hepatic glutathione synthesis

PubMed Central

Li, Ling; Zhang, Guo-Fang; Lee, Kwangwon; Lopez, Rocio; Previs, Stephen F.; Willard, Belinda; McCullough, Arthur; Kasumov, Takhar

2017-01-01

Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR−/− mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the 2H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P < 0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P <0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the 2H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases. PMID:27036364

A mathematical modelling approach to assessing the reliability of biomarkers of glutathione metabolism.

PubMed

Geenen, Suzanne; du Preez, Franco B; Reed, Michael; Nijhout, H Frederik; Kenna, J Gerry; Wilson, Ian D; Westerhoff, Hans V; Snoep, Jacky L

2012-07-16

One of the main pathways for the detoxification of reactive metabolites in the liver involves glutathione conjugation. Metabolic profiling studies have shown paradoxical responses in glutathione-related biochemical pathways. One of these is the increase in 5-oxoproline and ophthalmic acid concentrations with increased dosage of paracetamol. Experimental studies have thus far failed to resolve these paradoxes and the robustness of how these proposed biomarkers correlate with liver glutathione levels has been questioned. To better understand how these biomarkers behave in the glutathione system a kinetic model of this pathway was made. By using metabolic control analysis and by simulating biomarker levels under a variety of conditions, we found that 5-oxoproline and ophthalmic acid concentrations may not only depend on the glutathione but also on the methionine status of the cell. We show that neither of the two potential biomarkers are reliable on their own since they need additional information about the methionine status of the system to relate them uniquely to intracellular glutathione concentration. However, when both biomarkers are measured simultaneously a direct inference of the glutathione concentration can be made, irrespective of the methionine concentration in the system. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of glutathione on sperm quality during liquid storage in boars.

PubMed

Zhang, Xiao-Gang; Liu, Qi; Wang, Li-Qiang; Yang, Gong-She; Hu, Jian-Hong

2016-10-01

The aim of this study was to investigate the effects of different concentrations of glutathione in Modena on boar sperm quality during liquid storage at 17°C. Boar semen samples were collected and diluted with Modena containing different concentrations (0, 1, 5, 10, 15 mmol/L) of glutathione. Sperm motility, effective survival period, plasma membrane integrity, acrosome integrity, total antioxidant capacity (T-AOC) activity, malondialdehyde (MDA) content and hydrogen peroxide (H 2 O 2 ) content were measured and analyzed. The results showed that Modena supplemented with 1, 5 and 10 mmol/L glutathione improved sperm motility, effective survival period, plasma membrane integrity and T-AOC, and decreased MDA content and H 2 O 2 content. Meanwhile, the semen sample diluted with Modena containing 1 mmol/L glutathione achieved optimum effect, and effective survival period was 6.1 days. After 5 days preservation, sperm motility, plasma membrane integrity and T-AOC of the group treated with 1 mmol/L glutathione were all higher than that of other groups. Meanwhile, MDA content and H 2 O 2 content were lower than that of other groups. In conclusion, Modena supplemented with glutathione decreased the oxidative stress and improved the quality of boar semen during liquid storage at 17°C, and 1 mmol/L concentration was the optimum concentration. © 2016 Japanese Society of Animal Science. © 2016 Japanese Society of Animal Science.

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

PubMed

Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

Anaerobic bacteremia in a neutropenic patient with oral mucositis.

PubMed

Vidal, A M; Sarria, J C; Kimbrough, R C; Keung, Y K

2000-03-01

An increasing number of anaerobic bloodstream infections in neutropenic cancer patients have been reported in the last decade. The type of anaerobes isolated from most of these patients suggests an oral source of infection. We describe a case of anaerobic bacteremia in a neutropenic patient with oral mucositis that highlights the importance of considering these organisms when selecting empiric prophylactic or therapeutic antimicrobial regimens, especially in the setting of periodontal disease or oral mucositis.

The effect of oral mucositis on morbidity and mortality in bone marrow transplant.

PubMed

Gabriel, Don A; Shea, Thomas; Olajida, Oludamilola; Serody, Jonathan S; Comeau, Terrance

2003-12-01

Oral mucosal ulceration is a frequent complication in bone marrow transplantation, resulting from epithelial injury caused by cytotoxic chemotherapy and radiation conditioning, as well as from pre-existing infection. Oral mucositis causes pain, interferes with patient nutrition, and can lead to systemic infection and other complications that increase patient morbidity and mortality; this complication also markedly increases the expense of bone marrow transplantation. A variety of interventions have been assessed for preventing oral mucositis or reducing the severity of mucositis and its sequelae. These include meticulous pretransplantation and ongoing mouth care, calcium phosphate solution, near-infrared light and lower-energy laser treatment, interleukin-11, sucralfate, oral glutamine, granulocyte-macrophage colony-stimulating factor rinse, tretinoin, and keratinocyte growth factor; particularly promising results have been observed with use of the cytoprotectant/radioprotectant agent amifostine. Reduction in the severity and duration of oral mucositis and its sequelae in patients undergoing bone marrow transplantation can have a substantial impact on morbidity and mortality and cost of care. Further systematic evaluation of approaches to prevention and management of oral mucositis is necessary to define optimal strategies in the transplantation setting.

Formation of 5-Oxoproline from Glutathione in Erythrocytes by the γ-Glutamyltranspeptidase-Cyclotransferase Pathway

PubMed Central

Palekar, Anil G.; Tate, Suresh S.; Meister, Alton

1974-01-01

γ-Glutamyltranspeptidase activity was demonstrated in the membrane fraction of rabbit erythrocytes. The activity observed (with glutathione and various amino-acid acceptors) was similar in magnitude to that of the γ-glutamylcyclotransferase and γ-glutamylcysteine synthetase activities found in the soluble fraction of the cell. No transpeptidase activity was observed with either γ-glutamyl p-nitroanilide or oxidized glutathione in contrast to the rabbit-kidney enzyme for which these compounds and glutathione serve as substrates. Erythrocyte suspensions and hemolysates formed 5-oxoproline (pyroglutamate; pyrrolidone carboxylate); the rate of 5-oxoproline formation from glutathione by hemolysates was increased by addition of methionine. The findings indicate that 5-oxoproline is an end-product of glutathione metabolism in erythrocytes, and that 5-oxoproline passes out of the erythrocyte and is metabolized in other tissues. The observed rate of 5-oxoproline formation is consistent with the conclusion that the γ-glutamyltranspeptidase-cyclotransferase pathway, together with the synthesis of glutathione from glycine, cysteine, and glutamate, account for a large fraction of the observed amino-acid turnover of erythrocyte glutathione. PMID:4150022

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

PubMed Central

Rinsma, Nicolaas F.; Farré, Ricard; Troost, Fred J.; Elizalde, Montserrat; Keszthelyi, Daniel; Helyes, Zsuzsanna; Masclee, Ad A.; Conchillo, José M.

2017-01-01

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients. PMID:28534850

Prolapse of inverted ileal loops through a patent vitellointestinal duct

PubMed Central

Pathak, Ashish; Agarwal, Nitin; Singh, Poonam; Dhaneria, Mamta

2015-01-01

We report a case of a prolapsed patent vitellointestinal duct (PVID) in a 2-month-old girl child who presented with sudden increase in size of a polypoidal lesion into a large, ‘Y’-shaped reddish, prolapsing lesion, discharging gaseous and faecal matter at her umbilicus. The lesion was diagnosed as a prolapse of inverted ileal loops through the PVID. The child had no associated congenital anomalies. A transumbilical exploration was performed, followed by wedge resection and anastomosis. The child tolerated the procedure well and the postoperative course was uneventful. If the omphalomesenteric duct fails to obliterate a range of congenital defects related to the umbilicus, it can become clinically apparent. Meckel's diverticulum is the commonest of these defects but is most often asymptomatic. PVID is the most common symptomatic anomaly of the patent omphalomesenteric duct and requires prompt surgical correction to avoid complications. PMID:26494719

Prolapse of inverted ileal loops through a patent vitellointestinal duct.

PubMed

Pathak, Ashish; Agarwal, Nitin; Singh, Poonam; Dhaneria, Mamta

2015-10-22

We report a case of a prolapsed patent vitellointestinal duct (PVID) in a 2-month-old girl child who presented with sudden increase in size of a polypoidal lesion into a large, 'Y'-shaped reddish, prolapsing lesion, discharging gaseous and faecal matter at her umbilicus. The lesion was diagnosed as a prolapse of inverted ileal loops through the PVID. The child had no associated congenital anomalies. A transumbilical exploration was performed, followed by wedge resection and anastomosis. The child tolerated the procedure well and the postoperative course was uneventful. If the omphalomesenteric duct fails to obliterate a range of congenital defects related to the umbilicus, it can become clinically apparent. Meckel's diverticulum is the commonest of these defects but is most often asymptomatic. PVID is the most common symptomatic anomaly of the patent omphalomesenteric duct and requires prompt surgical correction to avoid complications. 2015 BMJ Publishing Group Ltd.

Starch source influences dietary glucose generation at the mucosal α-glucosidase level.

PubMed

Lin, Amy Hui-Mei; Lee, Byung-Hoo; Nichols, Buford L; Quezada-Calvillo, Roberto; Rose, David R; Naim, Hassan Y; Hamaker, Bruce R

2012-10-26

The quality of starch digestion, related to the rate and extent of release of dietary glucose, is associated with glycemia-related problems such as diabetes and other metabolic syndrome conditions. Here, we found that the rate of glucose generation from starch is unexpectedly associated with mucosal α-glucosidases and not just α-amylase. This understanding could lead to a new approach to regulate the glycemic response and glucose-related physiologic responses in the human body. There are six digestive enzymes for starch: salivary and pancreatic α-amylases and four mucosal α-glucosidases, including N- and C-terminal subunits of both maltase-glucoamylase and sucrase-isomaltase. Only the mucosal α-glucosidases provide the final hydrolytic activities to produce substantial free glucose. We report here the unique and shared roles of the individual α-glucosidases for α-glucans persisting after starch is extensively hydrolyzed by α-amylase (to produce α-limit dextrins (α-LDx)). All four α-glucosidases share digestion of linear regions of α-LDx, and three can hydrolyze branched fractions. The α-LDx, which were derived from different maize cultivars, were not all equally digested, revealing that the starch source influences glucose generation at the mucosal α-glucosidase level. We further discovered a fraction of α-LDx that was resistant to the extensive digestion by the mucosal α-glucosidases. Our study further challenges the conventional view that α-amylase is the only rate-determining enzyme involved in starch digestion and better defines the roles of individual and collective mucosal α-glucosidases. Strategies to control the rate of glucogenesis at the mucosal level could lead to regulation of the glycemic response and improved glucose management in the human body.

Changes in glutathione redox cycle during diapause determination and termination in the bivoltine silkworm, Bombyx mori.

PubMed

Zhao, Lin-Chuan; Hou, Yi-Sheng; Sima, Yang-Hu

2014-02-01

To explore whether glutathione regulates diapause determination and termination in the bivoltine silkworm Bombyx mori, we monitored the changes in glutathione redox cycle in the ovary of both diapause- and nondiapause-egg producers, as well as those in diapause eggs incubated at different temperatures. The activity of thioredoxin reductase (TrxR) was detected in ovaries but not in eggs, while neither ovaries nor eggs showed activity of glutathione peroxidase. A lower reduced glutathione/oxidized glutathione (GSH/GSSG) ratio was observed in the ovary of diapause-egg producers, due to weaker reduction of oxidized glutathione (GSSG) to the reduced glutathione (GSH) catalyzed by glutathione reductase (GR) and TrxR. This indicates an oxidative shift in the glutathione redox cycle during diapause determination. Compared with the 25°C-treated diapause eggs, the 5°C-treated diapause eggs showed lower GSH/GSSG ratio, a result of stronger oxidation of GSH catalyzed by thioredoxin peroxidase and weaker reduction of GSSG catalyzed by GR. Our study demonstrated the important regulatory role of glutathione in diapause determination and termination of the bivoltine silkworm. © 2013 Institute of Zoology, Chinese Academy of Sciences.

Subcellular distribution of glutathione and its dynamic changes under oxidative stress in the yeast Saccharomyces cerevisiae

PubMed Central

Zechmann, Bernd; Liou, Liang-Chun; Koffler, Barbara E; Horvat, Lucija; Tomašić, Ana; Fulgosi, Hrvoje; Zhang, Zhaojie

2011-01-01

Glutathione is an important antioxidant in most prokaryotes and eukaryotes. It detoxifies reactive oxygen species and is also involved in the modulation of gene expression, in redox signaling, and in the regulation of enzymatic activities. In this study, the subcellular distribution of glutathione was studied in Saccharomyces cerevisiae by quantitative immunoelectron microscopy. Highest glutathione contents were detected in mitochondria and subsequently in the cytosol, nuclei, cell walls, and vacuoles. The induction of oxidative stress by hydrogen peroxide (H2O2) led to changes in glutathione-specific labeling. Three cell types were identified. Cell types I and II contained more glutathione than control cells. Cell type II differed from cell type I in showing a decrease in glutathione-specific labeling solely in mitochondria. Cell type III contained much less glutathione contents than the control and showed the strongest decrease in mitochondria, suggesting that high and stable levels of glutathione in mitochondria are important for the protection and survival of the cells during oxidative stress. Additionally, large amounts of glutathione were relocated and stored in vacuoles in cell type III, suggesting the importance of the sequestration of glutathione in vacuoles under oxidative stress. PMID:22093747

Serologic and mucosal immune response to rotavirus infection in the rabbit model.

PubMed Central

Conner, M E; Gilger, M A; Estes, M K; Graham, D Y

1991-01-01

We examined the humoral immune response to rotavirus infection in specific pathogen-free rabbits inoculated and challenged orally with rabbit Ala rotavirus (7.5 x 10(5) to 1 x 10(7) PFU). The humoral immune response in both serologic and mucosal samples was monitored by using total antibody enzyme-linked immunosorbent assays (ELISAs), isotype-specific ELISAs, and plaque reduction neutralization assays. Following a primary infection, all rabbits shed virus and serologic and mucosal antibody responses were initially detected by 1 week postinoculation. Intestinal immunoglobulin M was detected by 3 days postinoculation, and secretory immunoglobulin A was detected by 6 days postinoculation. Following challenge, rabbits were protected (no detectable virus shedding) from infection. An anamnestic immune response was observed only with mucosal neutralizing antibodies, and all serologic and mucosal immune responses persisted at high levels until at least 175 days postchallenge (204 days postinoculation). Detection of neutralization responses was influenced by the virus strain used in the neutralization assay; all inoculated rabbits developed detectable serum and intestinal neutralizing antibodies against the infecting (Ala) virus strain. Neutralization activity in both serum and mucosal samples was generally, but not exclusively, homotypic (VP7 serotype 3) after both primary and challenge inoculations with Ala virus. Heterotypic serum neutralization activity was observed with serotype 8 (9 of 12 rabbits) and 9 (12 of 12 rabbits) viruses and may be based on reactivity with the outer capsid protein VP4 or on a shared epitope in the C region of VP7. Comparisons of heterologous (serotype 3) and heterotypic neutralizing responses in mucosal and serologic samples revealed that 43% (21 of 49) of the responses were discordant. In 19 of 49 (39%) of these cases, a heterotypic serologic response was seen in the absence of a heterotypic mucosal response, but in 2 of 49 (4%) instances, a

Palifermin in the management of mucositis in hematological malignancies: current evidences and future perspectives.

PubMed

Niscola, Pasquale; Scaramucci, Laura; Giovannini, Marco; Ales, Micaela; Bondanini, Francesco; Cupelli, Luca; Dentamaro, Teresa; Lamanda, Michela; Natale, Giuseppina; Palumbo, Roberto; Romani, Claudio; Tendas, Andrea; Tolu, Barbara; Violo, Leano; de Fabritiis, Paolo

2009-10-01

In the management of hematological malignancies, chemotherapy-induced mucositis is an increasingly recognized problem, leading to potentially severe clinical complications, treatment delays, increased costs and impairment of patient's quality of life. Many forms of cytotoxic treatments given in this setting may induce several degrees of mucositis. In particular, conditioning therapy with hematopoietic stem cell transplantation (HSCT) induces a disruption of the mucosal barrier function throughout the entire gastrointestinal tract facilitating the spreading of bacteria and endotoxin with subsequent increased risk of septicemia and, in the allogeneic setting, a worsening of Graft Versus Host Disease (GVHD). To review the role of palifermin and of other existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology in the setting of hematological malignancies. We searched for palifermin and mucositis of any region of the gastrointestinal tract using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are highly required. In this regard, palifermin (recombinant human keratinocyte growth factor) has been demonstrated to reduce the severity and the duration of oral mucositis and to significantly improve several treatment outcomes in patients submitted to autologous HSCT; data are insufficient to recommend its use in the non-autologous HSCT settings, although interesting properties of this agent deserves other investigations in order to explore other possible indications.

Effects of feeding corn naturally contaminated with aflatoxin on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of Na+, K+-ATPase in ducklings.

PubMed

Abbasi, Farzana; Liu, Jingbo; Zhang, Hongfu; Shen, Xiaoyun; Luo, Xuegang

2018-01-01

A 14-d trial was conducted to determine the effects of feeding corn naturally contaminated with aflatoxin B 1 (AFB 1 ) on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of Na + , K + -ATPase in ducklings. A total of 704 ducklings were blocked on the basis of sex and body weight (BW), and then allocated randomly to one of the following two treatments: i) CON, basal diet and ii) AFB 1 , diets with 100% of normal corn replaced with AFB 1 contaminated corn. There were 22 pens per treatment and 16 birds per pen. The concentration of AFB 1 was 195.4 and 124.35 μg/kg in the contaminated corn and AFB 1 diet, respectively. The AFB 1 decreased average daily gain, average daily feed intake, d 7 BW, final BW in the whole trial, and feed conversion ratio (FCR) during d 8 to 14 and d 1 to 14 by 10% to 47% (p<0.05), while FCR during d 1 to 7 was increased (p<0.05). AFB 1 did not affect mortality to 7 d of age, and then increased to 5.8% from 8 to 14 d of age (p<0.01). Apparent ileal gross energy digestibility was reduced by AFB 1 , whereas apparent ileal digestibility of dry matter, nitrogen, and amino acid was improved (p<0.01). Feeding AFB 1 diets increased serum concentration of leptin and insulin-like growth factors-1 (IGF-1) (p<0.05), but had no effect on neuropeptide Y, ghrelin, cholecystokinin-8 or insulin (p>0.05). Dietary treatments did not influence relative expression of jejunal Na + , K + -ATPase gene (p>0.05). Taken together, feeding corn naturally contaminated with AFB 1 reduced growth performance, improved apparent ileal digestibility, and affected serum leptin and IGF-1 in ducklings from d 1 to 14.

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals.

PubMed

Bailey, Ryan S; Casey, Kevin P; Pawar, Sachin S; Garcia, Guilherme J M

2017-01-01

Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy individuals. Healthy adult volunteers first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in 2 locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Nasal mucosal temperature and subjective patency scores in healthy individuals. The 22 healthy adult volunteers (12 [55%] male; mean [SD] age, 28.3 [7.0] years) had a mean (SD) NOSE score of 5.9 (8.4) (range, 0-30) and unilateral VAS score of 1.2 (1.4) (range, 0-5). The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (mean [SD] change in temperature, 6.2°C [2.6°C]) than during resting breathing (mean [SD] change in temperature, 4.2°C [2.3°C]) in both locations (P < .001). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side visual analog scale score (Pearson r = -0.55; 95% CI, -0.79 to -0.17; P = .008) and NOSE score (Pearson r = -0.47; 95% CI, -0.74 to -0.06; P = .03). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower (mean of 1.5°C lower) in the first cavity to be measured, which was the right cavity in all

Shear properties of vocal fold mucosal tissues and their effect on vocal fold oscillation

NASA Astrophysics Data System (ADS)

Chan, Roger Wai Kai

Viscoelastic shear properties of vocal fold mucosal tissues and phonosurgical biomaterials were measured with a parallel-plate rotational rheometer. Elastic, viscous and damping properties were quantified as a function of frequency (0.01 Hz to 15 Hz) for human vocal fold mucosal tissues (N = 15), implantable biomaterials commonly used in the treatment of vocal fold paralysis (Teflon, gelatin, and collagen) (the non-mucosal group), and biomaterials currently or potentially useful in the treatment of vocal fold mucosal defects (adipose tissue or fat, hyaluronic acid, and fibronectin) (the mucosal group). It was found that intersubject differences as large as an order of magnitude were often observed for the shear properties of vocal fold mucosal tissues, part of which may be age- and gender-related. Shear properties of the non-mucosal group biomaterials were often much higher than those of the mucosal group biomaterials, which were relatively close to the shear properties of mucosal tissues. Viscoelastic and rheological modeling showed that shear properties of human vocal fold mucosa may be described by a quasi-linear viscoelastic theory and a statistical network theory, based upon which extrapolations to audio frequencies were possible. A theory of small-amplitude vocal fold oscillation was revisited to describe the effects of tissue shear properties on vocal fold oscillation and phonation threshold pressure, a measure of the 'ease' of phonation and an objective indication of vocal function. It was found that phonation threshold pressure is directly related to the viscous shear modulus or the 'effective damping modulus', a concept proposed to quantify the effective amount of damping in vocal fold oscillation. The mucosal group biomaterials were incorporated into the artificial vocal fold mucosa of a physical model in order to empirically assess their effects on phonation threshold pressure. Results showed that higher threshold pressures were consistently observed

Oral mucosal melanoma treated with carbon ion radiotherapy: a case report.

PubMed

Musha, Atsushi; Saitoh, Jun-Ichi; Shirai, Katsuyuki; Yokoo, Satoshi; Ohno, Tatsuya; Nakano, Takashi

2016-10-18

Oral mucosal melanoma is a rare disease with a relatively poor prognosis. Carbon ion radiotherapy has been shown to be effective against radiotherapy-resistant tumors owing to its excellent dose concentration and high biological effect. Our patient was a 66-year-old Japanese man with oral mucosal melanoma of his right maxillary gingiva (T4aN0M0). He received carbon ion radiotherapy at 57.6 Gy (relative biological effectiveness) in 16 fractions for 4 weeks. Concomitant chemotherapy (dacarbazine + nimustine + vincristine) was administered at the same time as carbon ion radiotherapy initiation. Two courses of adjuvant chemotherapy were given after carbon ion radiotherapy. Although he experienced grade 2 acute oral mucositis, his symptoms improved within a few weeks of undergoing carbon ion radiotherapy. He was alive at the time of reporting, 35 months after treatment, without any recurrence. Late toxicity has not been observed. Carbon ion radiotherapy for oral mucosal melanoma resulted in a good local effect.

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues

PubMed Central

Lai, Samuel K.; Wang, Ying-Ying; Hanes, Justin

2009-01-01

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues. PMID:19133304

Glutathione cycle activity and pyridine nucleotide levels in oxidant-induced injury of cells.

PubMed Central

Schraufstätter, I U; Hinshaw, D B; Hyslop, P A; Spragg, R G; Cochrane, C G

1985-01-01

Exposure of target cells to a bolus of H2O2 induced cell lysis after a latent period of several hours, which was prevented only when the H2O2 was removed within the first 30 min of injury by addition of catalase. This indicated that early metabolic events take place that are important in the fate of the cell exposed to oxidants. In this study, we described two early and independent events of H2O2-induced injury in P388D1 macrophagelike tumor cells: activation of the glutathione cycle and depletion of cellular NAD. Glutathione cycle and hexose monophosphate shunt (HMPS) were activated within seconds after the addition of H2O2. High HMPS activity maintained glutathione that was largely reduced. However, when HMPS activity was inhibited--by glucose depletion or by incubation at 4 degrees C--glutathione remained in the oxidized state. Total pyridine nucleotide levels were diminished when cells were exposed to H2O2, and the breakdown product, nicotinamide, was recovered in the extracellular medium. Intracellular NAD levels fell by 80% within 20 min of exposure of cells to H2O2. The loss of NADP(H) and stimulation of the HMPS could be prevented when the glutathione cycle was inhibited by either blocking glutathione synthesis with buthionine sulfoximine (BSO) or by inhibiting glutathione reductase with (1,3-bis) 2 chlorethyl-1-nitrosourea. The loss of NAD developed independently of glutathione cycle and HMPS activity, as it also occurred in BSO-treated cells. PMID:3840176

Effect of dietary nutrients on ileal endogenous losses of threonine, cysteine, methionine, lysine, leucine and protein in broiler chicks.

PubMed

Cerrate, S; Vignale, S K; Ekmay, R; England, J; Coon, C

2018-04-01

An isotope dose technique was utilized (i) to determine endogenous amino acid (AA) and protein losses and (ii) to propose adjusted values for AA requirements. The endogenous flow rate was calculated from the pool of enrichment in plasma AA, assuming similitude to enrichment of endogenous AA. In experiment 1, chicks were orally administered D4-lysine at 2% of estimated lysine intake from 16 to 24 days to find the isotopic steady state of the atom percent excess (APE) of lysine for plasma and jejunal and ileal digesta. The APE of D4-lysine in plasma, jejunal digesta and ileal digesta reached the isotopic steady state at 5.5, 3.4 and 2.0 days, respectively, by using the broken-line model. It was assumed that the isotopic steady state at 5 days identified for D4-lysine is also representative for the 15N-labeled AA. In experiment 2, chicks were fed diets from 1 to 21 days with increasing levels of fat (6%, 8%, 12%, 13% extract ether), protein (26%, 28.5%, 31% CP) or fiber (14%, 16%, 18% NDF) by adding poultry fat, soybean meal, blended animal protein or barley. Chicks were orally administered 15N-threonine, 15N-cysteine, 15N-methionine, 15N-lysine and 15N-leucine at 2% of estimated daily intake for 5 days from 17 to 21 days of age. Dietary nutrients influenced endogenous losses (EL), where dietary fat stimulated EL of lysine (P=0.06), leucine and protein (P=0.07); dietary protein enhanced EL of leucine and protein; and finally the dietary fiber increased EL of leucine. Dietary nutrients also affected apparent ileal digestibility (AID). Dietary fat increased AID of cysteine but decreased AID of lysine. Dietary protein reduced AID of protein, threonine, lysine and leucine, and similarly dietary fiber decreased AID of protein, threonine, methionine, lysine and leucine. In contrast, dietary fat or protein did not affect real ileal digestibility (RID) of protein and AA except threonine and leucine. The dietary fiber reduced the RID of protein, threonine and leucine. This

Multi-scale Finite Element Modeling of Eustachian Tube Function: Influence of Mucosal Adhesion

PubMed Central

Malik, J.E.; Swarts, J.D.; Ghadiali, S. N.

2017-01-01

The inability to open the collapsible Eustachian tube (ET) leads to the development of chronic Otitis Media (OM). Although mucosal inflammation during OM leads to increased mucin gene expression and elevated adhesion forces within the ET lumen, it is not known how changes in mucosal adhesion alter the biomechanical mechanisms of ET function. In this study, we developed a novel multi-scale finite element model of ET function in adults that utilizes adhesion spring elements to simulate changes in mucosal adhesion. Models were created for six adult subjects and dynamic patterns in muscle contraction were used to simulate the wave-like opening of the ET that occurs during swallowing. Results indicate that ET opening is highly sensitive to the level of mucosal adhesion and that exceeding a critical value of adhesion leads to rapid ET dysfunction. Parameter variation studies and sensitivity analysis indicate that increased mucosal adhesion alters the relative importance of several tissue biomechanical properties. For example, increases in mucosal adhesion reduced the sensitivity of ET function to tensor veli palatini muscle forces but did not alter the insensitivity of ET function to levator veli palatini muscle forces. Interestingly, although changes in cartilage stiffness did not significantly influence ET opening under low adhesion conditions, ET opening was highly sensitive to changes in cartilage stiffness under high adhesion conditions. Therefore, our multi-scale computational models indicate that changes in mucosal adhesion as would occur during inflammatory OM alter the biomechanical mechanisms of ET function. PMID:26891171

Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

PubMed

Tayyem, Abdel-Qader Mahmoud

2014-08-01

Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.